Tetrahydro-pyrimidoazepines as modulators of TRPV1
First Claim
Patent Images
1. A compound of Formula (I):
- wherein;
R1 is —
H;
—
NRaRb;
—
OH;
a —
C1-6alkyl, —
OC1-6alkyl, —
O-(saturated monocyclic cycloalkyl), —
OC1alkyl-(saturated monocyclic cycloalkyl), —
O-(saturated monocyclic heterocycloalkyl), —
O-phenyl, —
O-benzyl, —
S—
C1-6alkyl, —
S-(saturated monocyclic cycloalkyl), —
SC1alkyl-(saturated monocyclic cycloalkyl), —
S-(saturated monocyclic heterocycloalkyl), —
S-phenyl, —
S-benzyl, or —
SO2—
C1-6alkyl group unsubstituted or substituted with one or two moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, and halo substituents;
or a phenyl, monocyclic cycloalkyl, or monocyclic heteroaryl group unsubstituted or substituted with a —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent;
where Ra and Rb are each independently —
H;
—
C1-6alkyl;
a —
C2-3alkyl group substituted with a —
OH, —
OC1-4alkyl, —
NRcRd, or halo substituent;
or a saturated monocyclic cycloalkyl, —
C1alkyl-(saturated monocyclic cycloalkyl), saturated monocyclic heterocycloalkyl, —
C1alkyl-(saturated monocyclic heterocycloalkyl), phenyl, benzyl, or —
C1alkyl-(monocyclic heteroaryl) group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, and halo substituents;
or
Ra and Rb taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl or bridged bicyclic heterocycloalkyl group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
C1-4alkyl-OH, —
C12alkyl-OC1-2alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, halo, —
CO2H, and benzyl substituents;
where Rc and Rd are each independently —
H or —
C1-6alkyl;
or Rc and Rd taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Rp and Rq are each independently —
H or —
C1-6alkyl;
or Rp and Rq taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Re and Rf are each independently —
H or —
C1-6alkyl;
or Re and Rf taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
R2 is —
H or —
C1-6alkyl;
R3 is a monocyclic cycloalkyl, phenyl, benzyl, phenethyl, indanyl, thiazolyl, thiophenyl, pyridyl, pyridylmethyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, or tetrahydroisoquinolinyl group unsubstituted or substituted with one, two, or three Rg substituents;
where each Rg substituent is —
C1-6alkyl;
—
C1-4alkyl-OH unsubstituted or substituted with —
CF3;
saturated monocyclic cycloalkyl;
—
OH;
—
OC1-6alkyl;
phenoxy;
—
CN;
—
NO2;
—
N(Rh)Ri;
—
C1-4alkyl-N(Rh)Ri;
—
C(O)N(Rh)Ri;
—
N(Rh)C(O)Ri;
—
N(Rh)SO2C1-6alkyl;
—
C(O)C1-6alkyl;
—
S(O)0-2—
C1-6alkyl;
—
SO2CF3;
—
SO2N(Rh)Ri;
—
SCF3;
halo;
—
CF3;
—
OCF3;
—
CO2H;
—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CN;
—
C(Rj)(Rx)—
OH;
—
C(Rj)(Rx)—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CO2H;
—
C(Rj)(Rx)—
C(O)N(Rh)Ri;
phenyl;
or monocyclic heteroaryl;
or two adjacent Rg substituents taken together form —
OC1-2alkylO—
;
where Rh and Ri are each independently —
H or —
C1-6alkyl;
or Rhand Ri (when both are present) taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl group;
Rj is independently —
H, —
C1-6alkyl, or —
CF3;
Rx is —
H or —
C1-6alkyl;
or Rj and Rx taken together with the carbon to which they are attached form a monocyclic cycloalkyl ring;
and Ar is a phenyl, pyridyl, imidazolyl, pyrimidinyl, pyridazinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one, two, or three Rk substituents;
where each Rk substituent is independently —
C1-6alkyl, —
C1-2alkyl-OH, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, halo, —
CF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl;
or two adjacent Rk substituents taken together form —
OC1-2alkylO—
;
where Rl and Rm are each independently —
H, —
C1-6alkyl, saturated monocyclic cycloalkyl, or —
CF3;
or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite of such compound.
1 Assignment
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Accused Products
Abstract
Certain tetrahydro-pyrimidoazepine compounds are described, which are useful as TRPV1 modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by TRPV1. Thus, the compounds may be-administered to treat, e.g., pain, itch, cough, asthma, or inflammatory bowel disease.
66 Citations
115 Claims
-
1. A compound of Formula (I):
-
wherein;
R1 is —
H;
—
NRaRb;
—
OH;
a —
C1-6alkyl, —
OC1-6alkyl, —
O-(saturated monocyclic cycloalkyl), —
OC1alkyl-(saturated monocyclic cycloalkyl), —
O-(saturated monocyclic heterocycloalkyl), —
O-phenyl, —
O-benzyl, —
S—
C1-6alkyl, —
S-(saturated monocyclic cycloalkyl), —
SC1alkyl-(saturated monocyclic cycloalkyl), —
S-(saturated monocyclic heterocycloalkyl), —
S-phenyl, —
S-benzyl, or —
SO2—
C1-6alkyl group unsubstituted or substituted with one or two moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, and halo substituents;
or a phenyl, monocyclic cycloalkyl, or monocyclic heteroaryl group unsubstituted or substituted with a —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent;
where Ra and Rb are each independently —
H;
—
C1-6alkyl;
a —
C2-3alkyl group substituted with a —
OH, —
OC1-4alkyl, —
NRcRd, or halo substituent;
or a saturated monocyclic cycloalkyl, —
C1alkyl-(saturated monocyclic cycloalkyl), saturated monocyclic heterocycloalkyl, —
C1alkyl-(saturated monocyclic heterocycloalkyl), phenyl, benzyl, or —
C1alkyl-(monocyclic heteroaryl) group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, and halo substituents;
or
Ra and Rb taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl or bridged bicyclic heterocycloalkyl group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
C1-4alkyl-OH, —
C12alkyl-OC1-2alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, halo, —
CO2H, and benzyl substituents;
where Rc and Rd are each independently —
H or —
C1-6alkyl;
or Rc and Rd taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Rp and Rq are each independently —
H or —
C1-6alkyl;
or Rp and Rq taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Re and Rf are each independently —
H or —
C1-6alkyl;
or Re and Rf taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
R2 is —
H or —
C1-6alkyl;
R3 is a monocyclic cycloalkyl, phenyl, benzyl, phenethyl, indanyl, thiazolyl, thiophenyl, pyridyl, pyridylmethyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, or tetrahydroisoquinolinyl group unsubstituted or substituted with one, two, or three Rg substituents;
where each Rg substituent is —
C1-6alkyl;
—
C1-4alkyl-OH unsubstituted or substituted with —
CF3;
saturated monocyclic cycloalkyl;
—
OH;
—
OC1-6alkyl;
phenoxy;
—
CN;
—
NO2;
—
N(Rh)Ri;
—
C1-4alkyl-N(Rh)Ri;
—
C(O)N(Rh)Ri;
—
N(Rh)C(O)Ri;
—
N(Rh)SO2C1-6alkyl;
—
C(O)C1-6alkyl;
—
S(O)0-2—
C1-6alkyl;
—
SO2CF3;
—
SO2N(Rh)Ri;
—
SCF3;
halo;
—
CF3;
—
OCF3;
—
CO2H;
—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CN;
—
C(Rj)(Rx)—
OH;
—
C(Rj)(Rx)—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CO2H;
—
C(Rj)(Rx)—
C(O)N(Rh)Ri;
phenyl;
ormonocyclic heteroaryl;
ortwo adjacent Rg substituents taken together form —
OC1-2alkylO—
;
where Rh and Ri are each independently —
H or —
C1-6alkyl;
or Rhand Ri (when both are present) taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl group;
Rj is independently —
H, —
C1-6alkyl, or —
CF3;
Rx is —
H or —
C1-6alkyl;
or Rj and Rx taken together with the carbon to which they are attached form a monocyclic cycloalkyl ring;
and Ar is a phenyl, pyridyl, imidazolyl, pyrimidinyl, pyridazinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one, two, or three Rk substituents;
where each Rk substituent is independently —
C1-6alkyl, —
C1-2alkyl-OH, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, halo, —
CF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl;
or two adjacent Rk substituents taken together form —
OC1-2alkylO—
;
where Rl and Rm are each independently —
H, —
C1-6alkyl, saturated monocyclic cycloalkyl, or —
CF3;
or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite of such compound. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 101, 102)
wherein: -
R1 is —
H;
—
NRaRb;
a —
C1-6alkyl, —
OC1-6alkyl, —
S—
C1-6alkyl, or —
SO2—
C1-6alkyl group unsubstituted or substituted with a —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent;
or a monocyclic cycloalkyl group unsubstituted or substituted with a —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent;
where Ra and Rb each independently is —
H;
—
C1-6alkyl;
a —
C2-3alkyl group substituted with a —
OH, —
OC1-4alkyl, —
NRcRd, or halo substituent;
or a saturated monocyclic cycloalkyl, —
C1alkyl-(saturated monocyclic cycloalkyl), saturated monocyclic heterocycloalkyl, —
C1alkyl-(saturated monocyclic heterocycloalkyl), phenyl, or benzyl group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, and halo substituents;
or
Ra and Rb taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, halo, —
CO2H, and benzyl substituents;
where Rc and Rd are each independently —
H or —
C1-6alkyl;
or Rc and Rd taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Rp and Rq are each independently —
H or —
C1-6alkyl;
or Rp and Rq taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Re and Rf are each independently —
H or —
C1-6alkyl;
or Re and Rf taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
R2 is —
H or —
C1-6alkyl;
R3 is a phenyl, benzyl, phenethyl, indanyl, thiazolyl, thiophenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one, two, or three Rg substituents;
where each Rg substituent is —
C1-6alkyl, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rh)Ri, —
C(O)N(Rh)Ri, —
N(Rh)C(O)Ri, —
N(Rh)SO2C1-6alkyl, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rh)Ri, —
SCF3, halo, —
CF3, —
OCF3, —
CO2H, —
CO2C1-6alkyl, —
C(Rj)2—
CN, or —
C(Rj)2—
OH;
ortwo adjacent Rg substituents taken together form —
OC1-2alkylO—
;
where Rh and Ri are each independently —
H or —
C1-6alkyl;
where each Rj is independently —
H or —
C1-6alkyl;
and Ar is a phenyl, pyridyl, imidazolyl, pyrimidinyl, pyridazinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one, two, or three Rk substituents;
where each Rk substituent is independently —
C1-6alkyl, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, halo, —
CF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl;
ortwo adjacent Rk substituents taken together form —
OC1-2alkylO—
;
where Rl and Rmare each independently —
H, —
C1-6alkyl, or —
CF3;
or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite of such compound.
-
52. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R1 is —
- H.
-
53. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R1 is —
- NRaRb.
-
54. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R1 is a —
- C1-6alkyl group unsubstituted or substituted with a —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent.
- C1-6alkyl group unsubstituted or substituted with a —
-
55. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 54, wherein R1 is methyl or isopropyl.
-
56. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R1 is a methyl group substituted with a —
- OC1-4alkyl or —
NReRf substituent.
- OC1-4alkyl or —
-
57. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 56, wherein R1 is methoxymethyl or piperidinylmethyl.
-
58. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R1 is methoxy, methylsulfanyl, or methylsulfonyl.
-
59. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R1 is cyclopropyl.
-
60. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ra and Rb are each independently —
- H;
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, or hexyl;
an ethyl or propyl group substituted with an —
OC1-4alkyl or —
NRcRd substituent;
or a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclopentylmethyl, aziridinyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-1λ
6-thiomorpholin-4-yl, or phenyl group unsubstituted or substituted with a —
C1-6alkyl, —
OC1-4alkyl, or halo substituent.
- H;
-
61. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 53, wherein Ra and Rb are each independently —
- H;
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, or hexyl;
an ethyl or propyl group substituted with an —
OC1-4alkyl or —
NRcRd substituent;
or a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclopentylmethyl, aziridinyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-1λ
6-thiomorpholin-4-yl, or phenyl group unsubstituted or substituted with a —
C1-6alkyl, —
OC1-4alkyl, or halo substituent.
- H;
-
62. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ra and Rb are each independently —
- H, methyl, methoxyethyl, cyclopropyl, cyclopropylmethyl, 2-piperidin-1-yl-ethyl, or 2-dimethylamino-ethyl.
-
63. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ra and Rb taken together with their nitrogen of attachment form an aziridinyl, pyrrolidinyl, piperidinyl, 2-oxo-piperidin-1-yl, piperazinyl, oxo-piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-1λ
-
6-thiomorpholin-4-yl, 1,1-dioxo-1λ
6-[1,2]thiazinan-2-yl, or azepanyl group unsubstituted or substituted with a —
C1-6alkyl, —
OH, or —
CO2H substituent.
-
6-thiomorpholin-4-yl, 1,1-dioxo-1λ
-
64. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Rc and Rd are each independently —
- H, methyl, or ethyl.
-
65. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Rc and Rd taken together with their nitrogen of attachment form piperidinyl.
-
66. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Rp and Rq are each independently —
- H, methyl, or ethyl.
-
67. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Re and Rf are each independently —
- H, methyl, or ethyl.
-
68. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R2 is —
- H or methyl.
-
69. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 68, wherein R2 is —
- H.
-
70. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R3 is a phenyl, pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents.
-
71. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R3 is a pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents.
-
72. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R3 is a pyridyl, thiazolyl, or pyridazinyl group unsubstituted or substituted with one or two Rg substituents.
-
73. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R3 is a phenyl group substituted with one or two Rg substituents.
-
74. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R3 is a benzyl or phenethyl group unsubstituted or substituted with one or two Rg substituents.
-
75. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein R3 is a 2-pyridyl group unsubstituted or substituted with one Rg substituent.
-
76. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein each Rg substituent is independently —
- C1-6alkyl, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rh)Ri, —
C(O)N(Rh)Ri, —
N(Rh)C(O)Ri, —
N(Rh)SO2C1-6alkyl, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rh)Ri, —
SCF3, halo, —
CO2H, —
CO2C1-6alkyl, —
C(Rj)2—
CN, or —
C(Rj)2—
OH.
- C1-6alkyl, —
-
77. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein two adjacent Rg moieties taken together form —
- OC1-2alkylO—
.
- OC1-2alkylO—
-
78. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein each Rg substituent is independently isopropyl, tert-butyl, —
- CF3, chloro, —
OCF3, —
SO2NH2, —
OCH3, phenoxy, bromo, —
C(CH3)2—
CN, —
C(CH3)2—
OH, —
NO2, —
CN, —
NH2, —
C(O)CH3, —
SO2CF3, or —
SCF3;
or two adjacent Rg substituents taken together form —
OC1-2alkylO—
.
- CF3, chloro, —
-
79. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein each Rg substituent is independently isopropyl, tert-butyl, —
- CF3, chloro, —
C(CH3)2—
CN, —
C(CH3)2—
OH, or —
SO2CF3.
- CF3, chloro, —
-
80. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Rh and Ri are each independently —
- H, methyl, or ethyl.
-
81. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Rj is —
- H, methyl, or ethyl.
-
82. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is a phenyl group unsubstituted or substituted with one or two Rk substituents.
-
83. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is a phenyl group substituted with a —
- NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
SO2CH3, or —
SO2CF3 substituent.
- NO2, —
-
84. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is a fused-bicyclic heteroaryl group unsubstituted or substituted with one or two Rk substituents.
-
85. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is 2-pyridyl substituted with —
- CF3, —
NO2, or —
N(Rl)Rm.
- CF3, —
-
86. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is 2-pyridyl substituted with —
- Cl, —
Br, methyl, or —
SO2CH3.
- Cl, —
-
87. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is quinoxalinyl or phthalizinyl.
-
88. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Ar is a phenyl, pyridyl, pyrimidinyl, or fused-bicyclic heteroaryl group substituted on a carbon ring atom at a position ortho to the point of attachment with an Rk substituent.
-
89. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein each Rk substituent is independently —
- C2-6alkyl, —
OH, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl;
or two adjacent Rk substituents taken together form —
OC1-2alkylO—
.
- C2-6alkyl, —
-
90. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein each Rk substituent is independently —
- N(Rl)Rm, —
NO2, —
N(Rl)SO2CF3, or —
N(Rl)SO2CH3.
- N(Rl)Rm, —
-
91. A compound, pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite as defined in claim 51, wherein Rl and Rm are each independently —
- H, methyl, ethyl, or —
CF3.
- H, methyl, ethyl, or —
-
92. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
H, —
NRaRb, —
C1-6alkyl, —
O—
C1-6alkyl, —
S—
C1-6alkyl, —
SO2—
C1-6alkyl, —
CH2—
O—
C1-4alkyl, or —
CH2—
NReRf;
R2 is —
H;
R3 is a pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents; and
Ar is a phenyl group substituted with one or two Rk substituents.
- R1 is —
-
93. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
H, —
NRaRb, —
C1-6alkyl, —
O—
C1-6alkyl, —
S—
C1-6alkyl, —
SO2—
C1-6alkyl, —
CH2—
O—
C1-4alkyl, or —
CH2—
NReRf;
R2 is —
H;
R3 is a benzyl, phenethyl, indanyl, pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents; and
Ar is a phenyl group substituted with one or two Rk substituents, where each Rk substituent is —
C2-6alkyl, —
OH, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl, or two adjacent Rk substituents taken together form —
OC1-2alkylO—
.
- R1 is —
-
94. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
H, NRaRb, —
C1-6alkyl, —
O—
C1-6alkyl, —
S—
C1-6alkyl, —
SO2—
C1-6alkyl, —
CH2—
O—
C1-4alkyl, or —
CH2—
NReRf;
R2 is —
H;
R3 is a benzyl or phenethyl group unsubstituted or substituted with one or two Rg substituents; and
Ar is 2-pyridyl substituted with —
CF3, —
NO2, or —
N(Rl)Rm.
- R1 is —
-
95. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
C1-6alkyl;
R2 is —
H;
R3 is a phenyl, pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents; and
Ar is a phenyl, pyridyl, pyrimidinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one or two Rk substituents.
- R1 is —
-
96. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
H, —
NRaRb, —
C1-6alkyl, —
O—
C1-6alkyl, —
S—
C1-6alkyl, —
SO2—
C1-6alkyl, —
CH2—
O—
C1-4alkyl, or —
CH2—
NReRf;
R2 is —
H;
R3 is a phenyl, benzyl, phenethyl, indanyl, pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents; and
Ar is a fused-bicyclic heteroaryl group unsubstituted or substituted with one or two Rk substituents.
- R1 is —
-
97. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
NRaRb;
R2 is —
H;
R3 is a phenyl group substituted with one or two Rg substituents, where each Rg substituent is —
C1-6alkyl, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rh)Ri, —
C(O)N(Rh)Ri, —
N(Rh)C(O)Ri, —
N(Rh)SO2C1-6alkyl, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rh)Ri, —
SCF3, halo, —
CO2H, —
CO2C1-6alkyl, —
C(Rj)2—
CN, or —
C(Rj)2—
OH, or two adjacent Rg substituents taken together form —
OC1-2alkylO—
; and
Ar is a phenyl, pyridyl, pyrimidinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one or two Rk substituents.
- R1 is —
-
98. A compound or pharmaceutically acceptable salt as defined in claim 51, wherein:
- R1 is —
NRaRb;
R2 is —
H;
R3 is a phenyl, benzyl, phenethyl, indanyl, pyridyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl group unsubstituted or substituted with one or two Rg substituents; and
Ar is a phenyl group unsubstituted or substituted with one or two Rk substituents.
- R1 is —
-
101. A compound or pharmaceutically acceptable salt according to claim 1.
-
102. A compound or pharmaceutically acceptable salt according to claim 51.
-
-
99. A compound selected from the group consisting of:
-
(4-tert-Butyl-phenyl)-[7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-Trifluoromethyl-phenyl)-[7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetra-hydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-tert-Butyl-phenyl)-[2-cyclopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-Chloro-phenyl)-[2-cyclopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Cyclopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
(4-tert-Butyl-phenyl)-[2-phenyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Phenyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
(4-tert-Butyl-phenyl)-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(3-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethoxy-phenyl)-amine;
[2-(4-Fluoro-phenyl)-ethyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-(2-Chloro-phenyl)-ethyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(3,4-Dichloro-benzyl)-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-tert-Butyl-phenyl)-[2-methyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Methyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido-[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
(5-Trifluoromethyl-pyridin-2-yl)-[7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
Isoquinolin-1-yl-[7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Cyclopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-quinolin-3-yl-amine;
[2-Phenyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine;
[2-Methyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-phenoxy-phenyl)-amine;
(4-Trifluoromethyl-phenyl)-[7-(4-trifluoromethyl-pyrimidin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(7-Pyrimidin-2-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)-(4-trifluoromethyl-phenyl)-amine;
(7-Pyrazin-2-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)-(4-trifluoromethyl-phenyl)-amine;
(7-Quinoxalin-2-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)-(4-trifluoromethyl-phenyl)-amine;
[7-(3-Chloro-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
(4-tert-Butyl-phenyl)-[7-(6-chloro-5-methyl-pyrimidin-4-yl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-tert-Butyl-phenyl)-[7-(3-methyl-quinoxalin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-tert-Butyl-phenyl)-[2-isopropyl-7-(3-methyl-quinoxalin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Isopropyl-7-(3-methyl-quinoxalin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido-[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-quinoxalin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-methanesulfonyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
(4-tert-Butyl-phenyl)-(7-phthalazin-1-yl-6,7,8,9-tetrahydro-5H-pyrimido-[4,5-d]azepin-4-yl)-amine;
(4-tert-Butyl-phenyl)-[7-(5-methyl-pyrimidin-4-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine [2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
(4-tert-Butyl-phenyl)-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N2,N2-Dimethyl-N4-(6-trifluoromethyl-pyridin-3-yl)-7-(3-trifluoro-methyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2,N2-Dimethyl-N4-(5-trifluoromethyl-pyridin-2-yl)-7-(3-trifluoro-methyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-(3-Chloro-4-trifluoromethyl-phenyl)-N2,N2-dimethyl-7-(3-trifluoro-methyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
(4-Bromo-phenyl)-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-tert-Butyl-phenyl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N4-(4-tert-Butyl-phenyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2,N2-Dimethyl-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-(4-Chloro-phenyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-(4-Trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[2-Methylsulfanyl-7-(3trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Methanesulfonyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
N2-Phenyl-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-Cyclopropyl-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[2-Azetidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
1-[4-(4-Trifluoromethyl-phenylamino)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl]-piperidine-4-carboxylic acid;
N2-(2-Piperidin-1-yl-ethyl)-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoro-methyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
1-[4-(4-Trifluoromethyl-phenylamino)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl]-piperidin-4-ol;
[2-(4-Isopropyl-piperazin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
N2-(Tetrahydro-pyran-4-yl)-N4(4-trifluoromethyl-phenyl)-7-(3-trifluoro-methyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[2-Methoxy-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
N4-(3,4-Dichloro-phenyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-(4-Methoxy-3-trifluoromethyl-phenyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-{4-[2-Dimethylamino-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-2-methyl-propionitrile;
(4-tert-Butyl-phenyl)-[2-piperidin-1-ylmethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-tert-Butyl-phenyl)-[2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N4-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[2-Methyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
N4-Benzyl-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
4-[2-Dimethylamino-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzenesulfonamide;
N2,N2-Dimethyl-N4-(4-nitro-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-(3,4-Dichloro-benzyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyridin-2-yl)-amine;
[2-Methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine;
[2-Methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
4-[2-Dimethylamino-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
4-[2-Dimethylamino-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzonitrile;
N4-(4-Dimethylamino-phenyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
(3-Chloro-4-trifluoromethyl-phenyl)-[2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N4-(4-Methoxy-phenyl)-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-Indan-2-yl-N2,N2-dimethyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[7-(5-Amino-3-methyl-pyridin-2-yl)-2-isopropyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[7-(2-Amino-phenyl)-2-isopropyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(2-nitro-phenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[7-(3-Amino-pyridin-2-yl)-2-isopropyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-methyl-5-nitro-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-nitro-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
N-{2-[2-Isopropyl-4-(4-trifluoromethyl-phenylamino)-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepin-7-yl]-phenyl}-methanesulfonamide;
4-[4-(4-Trifluoromethyl-phenylamino)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl]-piperazin-2-one;
(R)-1-[4-(4-Trifluoromethyl-phenylamino)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl]-piperidin-3-ol;
[2-(4-Methyl-piperazin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
N2-(2-Methoxy-ethyl)-N2-methyl-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
(S)-1-[4-(4-Trifluoromethyl-phenylamino)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl]-piperidin-3-ol;
N2-Cyclopropylmethyl-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-ethanone;
4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzonitrile;
(3,4-Dichloro-benzyl)-[2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Piperazin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Thiomorpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethanesulfonyl-phenyl)-amine;
[2-(4-Benzyl-piperazin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethylsulfanyl-phenyl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-pyrimidin-4-yl-amine;
[2-Pyrrolidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-pyrimidin-2-yl-amine;
[2-(3,4-Dichloro-phenyl)-ethyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(3,4-Dichloro-phenyl)-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N-{2-[2-Isopropyl-4-(4-trifluoromethyl-phenylamino)-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepin-7-yl]-pyridin-3-yl}-methanesulfonamide;
N-{2-[2-Isopropyl-4-(4-trifluoromethyl-phenylamino)-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepin-7-yl]-phenyl}-methanesulfonamide;
2-{4-[2-Azetidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
2-{4-[2-Azepan-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol; and
N2-(2-Dimethylamino-ethyl)-N2-methyl-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
and pharmaceutically acceptable salts thereof.
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100. A compound selected from the group consisting of:
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N-{[4-Chloro-3-(trifluoromethyl)phenyl]methyl}-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-{[4-(trifluoromethyl)phenyl]methyl}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-(2-Fluorophenyl)ethyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-(2-Bromophenyl)ethyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[(2,6-Dichlorophenyl)methyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[(2-Chlorophenyl)methyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)cyclohexyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-(3-Chlorophenyl)ethyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-(4-Chlorophenyl)ethyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-(2,6-Dichlorophenyl)ethyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-{2-[2-(methyloxy)phenyl]ethyl}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N,N-Dimethyl-4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)benzamide;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Methyl-2-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanenitrile;
4-({2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)benzoic acid;
N-Biphenyl-4-yl-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-(4-Cyclohexylphenyl)-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-(4-piperidin-1-ylphenyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-(4-morpholin-4-ylphenyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-[4-(methylsulfanyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-(4-nitrophenyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-[4-(1-methylethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1,1-Dimethylethyl)-N-[4-(1,1-dimethylethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1,1-Dimethylethyl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[3-Fluoro-4-(trifluoromethyl)phenyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-(2,3-Dihydro-1H-inden-5-yl)-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-[4-(1,3-oxazol-5-yl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)-3-nitrophenyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Furan-2-yl-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-furan-2-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Furan-3-yl-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-furan-3-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
Benzo[1,2,5]thiadiazol-5-yl-[2-isopropyl-7-(3-trifluoromethyl-pyridin-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-(2-Thienyl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(3-Thienyl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-(4-methylphenyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(2-Methyl-1,3-thiazol-4-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N,N-Dimethyl-4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)benzenesulfonamide;
N-[2-Fluoro-4-(trifluoromethyl)phenyl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
1-[4-({2-Piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]ethanone;
N-[3-Fluoro-4-(trifluoromethyl)phenyl]-2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N,N-Dimethyl-4-({2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)benzenesulfonamide;
N-[4-(1,1-Dimethylethyl)-3-nitrophenyl]-2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(Methylsulfanyl)phenyl]-2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-pyridin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
((2-Fluoro-4-trifluoromethyl-phenyl)-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-Pyridin-4-yl-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-pyridin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-pyridin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Pyridin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-pyridin-2-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Pyridin-2-yl-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-pyridin-2-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
Methyl 2-methyl-2-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanoate;
Methyl 2-methyl-2-[4-({2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanoate;
2-Pyridin-3-yl-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[4-({2-Piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propan-2-ol;
2-[4-({2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propan-2-ol;
1,1,1-Trifluoro-2-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propan-2-ol;
1,1,1-Trifluoro-2-[4-({2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propan-2-ol;
2-Methyl-2-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propan-1-ol;
1-[4-({2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]ethanol;
2,2,2-Trifluoro-1-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]ethanol;
2-Methyl-2-[4-({2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanoic acid;
4-({2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)benzoic acid;
2-Methyl-2-[4-({2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanoic acid;
2-(1-Methylethyl)-N-(5-methylpyrazin-2-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[6-Chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(6-methoxy-5-trifluoromethyl-pyridin-2-yl)-amine;
2-Pyridin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyrazin-2-yl)-amine;
[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyrazin-2-yl)-amine;
2-(4-Methylpiperazin-1-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azepan-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-[2-(Dimethylamino)ethyl]-N2-methyl-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-Methyl-N2-[2-(methyloxy)ethyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-Azetidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-{2-(1-Methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}benzene-1,4-diamine;
4-(1,1-Dimethylethyl)-N1-{2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}benzene-1,3-diamine;
4-(1,1-Dimethylethyl)-N1-{2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}benzene-1,3-diamine;
7-[5-Amino-3-(trifluoromethyl)pyridin-2-yl]-N-[4-(1,1-dimethylethyl)phenyl]-2-(1-methylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-(methylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-Chloro-4-(trifluoromethyl)phenyl]-2-(methylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Methylsulfanyl)-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Methylsulfanyl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Methylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-(methylsulfonyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Methylsulfonyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Methylsulfonyl)-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-N-[4-(methylsulfonyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
Methyl 5-chloro-6-[2-(methylsulfonyl)-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl]pyridine-3-carboxylate;
2-(1,1-Dioxido-1,2-thiazinan-2-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-[2-(Methyloxy)ethyl]-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-[3-(Methyloxy)piperidin-1-yl]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-{(2S)-2-[(Methyloxy)methyl]pyrrolidin-1-yl}-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-(Furan-2-ylmethyl)-N2-methyl-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-Azetidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2,N2-Dimethyl-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-[2-(Dimethylamino)ethyl]-N2-methyl-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-(4-Methylpiperazin-1-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-(4-methylpiperazin-1-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azepan-1-yl-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azepan-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azepan-1-yl-N-[3-chloro-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-[2-(Dimethylamino)ethyl]-N2-methyl-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-[3-Chloro-4-(trifluoromethyl)phenyl]-N2-[2-(dimethylamino)ethyl]-N2-methyl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-[(3,4-Dichlorophenyl)methyl]-N2-[2-(dimethylamino)ethyl]-N2-methyl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-Methyl-N2-[2-(methyloxy)ethyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-[3-Chloro-4-(trifluoromethyl)phenyl]-N2-methyl-N2-[2-(methyloxy)ethyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-[(3,4-Dichlorophenyl)methyl]-N2-methyl-N2-[2-(methyloxy)ethyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-Azetidin-1-yl-N-[3-chloro-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azetidin-1-yl-N-[(3,4-dichlorophenyl)methyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(2,6-Dimethylmorpholin-4-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(2R,6S)-2,6-Dimethylmorpholin-4-yl]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1,4-Oxazepan-4-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(3,3-Difluoropiperidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(4-Methylpiperidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(3-Methyl piperidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(3,3-Difluoroazetidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(4,4-Difluoropiperidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(3,3-Difluoropyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(2-Methylpyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-(1,4-oxazepan-4-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(2-Methyl piperidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1,1-Dioxidothiomorpholin-4-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-pyrrolidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azetidin-1-yl-N-[4-(1,1-dimethylethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[(3,4-Dichlorophenyl)methyl]-2-piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-(4-methylpiperazin-1-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Azepan-1-yl-N-[4-(1,1-dimethylethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-[2-(Dimethylamino)ethyl]-N4-[4-(1,1-dimethylethyl)phenyl]-N2-methyl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-Azepan-1-yl-N-[(3,4-dichlorophenyl)methyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[(3,4-Dichlorophenyl)methyl]-2-(4-methylpiperazin-1-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N4-[4-(1,1-Dimethylethyl)phenyl]-N2-methyl-N2-[2-(methyloxy)ethyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N-[3-Chloro-4-(trifluoromethyl)phenyl]-2-pyrrolidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
[1-(4-{[4-(Trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)piperidin-2-yl]methanol;
[(2S)-1-(4-{[4-(Trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)pyrrolidin-2-yl]methanol;
[(2R)-1-(4-{[4-(Trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)pyrrolidin-2-yl]methanol;
[(2S)-1-(7-[3-(Trifluoromethyl)pyridin-2-yl]-4-{[5-(trifluoromethyl)pyridin-2-yl]amino}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)pyrrolidin-2-yl]methanol;
N2-[(3R)-Tetrahydrofuran-3-yl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N4-[4-(1,1-Dimethylethyl)phenyl]-N2-[(3R)-tetrahydrofuran-3-yl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-(Tetrahydro-furan-3-yl)-N4-(4-trifluoromethyl-phenyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-Methyl-N2-(1-methylethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-Cyclohexyl-N2-methyl-N4-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-(7-Azabicyclo[2.2.1]hept-7-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[2-(1-Methylethyl)pyrrolidin-1-yl]-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-(Cyclohexylmethyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[4-(4-{[4-(Trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)morpholin-2-yl]methanol;
N2-Methyl-N2-(1-methylethyl)-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
[4-(4-{[2-Methyl-4-(trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)morpholin-2-yl]methanol;
2-[2-(1-Methylethyl)pyrrolidin-1-yl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-Cyclohexyl-N2-methyl-7-[3-(trifluoromethyl)pyridin-2-yl]-N4-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
2-[(2S or 2R)-2-Methylpiperidin-1-yl]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(2S or 2R)-2-Methylpiperidin-1-yl]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N2-(2-Methyl phenyl)-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-(3-Methylphenyl)-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N2-(4-Methylphenyl)-N4-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine-2,4-diamine;
N-{2-[2-(1-Methylethyl)-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl]pyridin-3-yl}methanesulfonamide;
2-(1-Methylethyl)-7-[3-(methylsulfonyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
7-[3-(Methylsulfonyl)pyridin-2-yl]-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
7-(3-Aminopyridin-2-yl)-N-[4-(1,1-dimethylethyl)phenyl]-2-(1-methylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
7-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]-N-[4-(1,1-dimethylethyl)phenyl]-2-(1-methylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
7-(5-Bromo-3-chloropyridin-2-yl)-N-[4-(1,1-dimethylethyl)phenyl]-2-(1-methylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
7-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]-2-(1-methylethyl)-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
5-Chloro-6-[2-(1-methylethyl)-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl]pyridine-3-carboxylic acid;
N-[4-(1,1-Dimethylethyl)phenyl]-2-(1-methylethyl)-7-(3-methyl-5-nitropyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-2-(1-methylethyl)-7-[5-nitro-3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(1-Methylethyl)-7-[5-nitro-3-(trifluoromethyl)pyridin-2-yl]-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-7-(5-fluoro-3-methylpyridin-2-yl)-2-(1-methylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(4-{[4-(Trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl)pyridine-3-carbonitrile;
2-(4-{[4-(Trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl)pyridine-3-carboxamide;
7-(3-Fluoropyridin-2-yl)-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(1,1-Dimethylethyl)phenyl]-7-[3-(ethylsulfonyl)pyridin-2-yl]-2-(1-methylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
7-[3-(Ethylsulfonyl)pyridin-2-yl]-2-piperidin-1-yl-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(2-Piperidin-1-yl-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl)pyridine-3-sulfonamide;
N-Cyclopropyl-2-(2-piperidin-1-yl-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl)pyridine-3-sulfonamide;
N-(1-Methylethyl)-2-(2-piperidin-1-yl-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl)pyridine-3-sulfonamide;
7-[3-(Ethylsulfonyl)pyridin-2-yl]-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(4-{[4-(Trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl)pyridine-3-sulfonamide;
Methyl 5-chloro-6-[2-(methylsulfanyl)-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl]pyridine-3-carboxylate;
2-(Methylsulfanyl)-7-[3-(methylsulfonyl)pyridin-2-yl]-N-[4-(trifluoromethyl)phenyl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
[7-(3-Ethanesulfonyl-pyridin-2-yl)-2-methylsulfanyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
{5-Chloro-6-[2-(methylsulfanyl)-4-{[4-(trifluoromethyl)phenyl]amino}-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepin-7-yl]pyridin-3-yl}methanol;
2-({[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}oxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexyloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclohexylethyl)oxy]-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclopentyloxy)-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Methyl piperidin-4-yl)oxy]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-Methyl-4-(trifluoromethyl)phenyl]-2-(tetrahydro-2H-pyran-4-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-Methyl-4-(trifluoromethyl)phenyl]-2-(tetrahydrofuran-3-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(Pyrrolidin-1-ylsulfonyl)phenyl]-2-(tetrahydrofuran-3-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-{[1-(1-Methylethyl)pyrrolidin-3-yl]oxy}-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclohexylethyl)oxy]-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclopropylethyl)oxy]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclohexylethyl)oxy]-7-[3-(trifluoromethyl)pyridin-2-yl-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclopentyloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclohexylethyl)oxy]-N-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclopropylethyl)oxy]-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Tetrahydro-2H-pyran-4-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-2-(tetrahydrofuran-3-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclopentyloxy)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclopropylethyl)oxy]-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexyloxy)-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Butyloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexyloxy)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-(1-Methyl-1,2,3,4-tetrahydroquinolin-7-yl)-2-(tetrahydro-2H-pyran-4-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-({[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}oxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Tetrahydrofuran-3-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclohexylethyl)oxy]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclopentyloxy)-N-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Cyclopropylethyl)oxy]-N-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[4-(Pyrrolidin-1-ylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yloxy)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cycloheptyloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclopentyloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexyloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Tetrahydro-2H-pyran-4-yloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Tetrahydrofuran-3-yloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Methylethyl)oxy]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Phenyloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Butyloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
4-{[4-(Trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-oll;
2-(Ethyloxy)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(Methyloxy)methyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Methyl-2-[4-({2-[(methyloxy)methyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]propanenitrile;
2-(Methylsulfonyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Phenylsulfanyl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Phenylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N-[2-Methyl-4-(trifluoromethyl)phenyl]-2-(phenylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Phenylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(Phenylmethyl)sulfanyl]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexylsulfanyl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Methylethyl)sulfanyl]-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
1-[(4-{[4-(Trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)sulfanyl]propan-2-ol;
[2-(2-Methyl-tetrahydro-furan-3-ylsulfanyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
[2-(2-Methyl-tetrahydro-furan-3-ylsulfanyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine;
2-[(Phenylmethyl)sulfanyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Methylethyl)sulfanyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
1-({7-[3-(Trifluoromethyl)pyridin-2-yl]-4-({4-[(trifluoromethyl)sulfonyl]phenyl}amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl}sulfanyl)propan-2-ol;
[2-(2-Methyl-tetrahydro-furan-3-ylsulfanyl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethanesulfonyl-phenyl)-amine;
N-[2-Methyl-4-(trifluoromethyl)phenyl]-2-[(phenylmethyl)sulfanyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexylsulfanyl)-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Methylethyl)sulfanyl]-N-[2-methyl-4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
1-[(4-{[2-Methyl-4-(trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)sulfanyl]propan-2-ol;
2,5-Anhydro-1,4-dideoxy-3-S-(4-{[2-methyl-4-(trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-3-thiopentitol;
2,5-Anhydro-1,4-dideoxy-3-S-(4-{[2-methyl-4-(trifluoromethyl)phenyl]amino}-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl)-3-thiopentitol;
2-[(Phenylmethyl)sulfanyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-(Cyclohexylsulfanyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-[(1-Methylethyl)sulfanyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-N-(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
1-({7-[3-(Trifluoromethyl)pyridin-2-yl]-4-[(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)amino]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl}sulfanyl)propan-2-ol;
2,5-Anhydro-1,4-dideoxy-3-thio-3-S-{7-[3-(trifluoromethyl)pyridin-2-yl]-4-[(1,4,4-trimethyl-1,2,3,4-tetrahydroquinolin-7-yl)amino]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-2-yl}pentitol;
2-(Propylsulfanyl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Methyl-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propionic acid methyl ester;
2-(1-Methylethyl)-N-(4-pyrrolidin-1-ylphenyl)-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
2-Piperidin-1-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine;
N,N-Dimethyl-4-({2-morpholin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)benzenesulfonamide;
1-[4-({2-Morpholin-4-yl-7-[3-(trifluoromethyl)pyridin-2-yl]-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl}amino)phenyl]ethanone;
(3-Chloro-4-trifluoromethyl-phenyl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-Methyl-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propionitrile;
2-Methyl-2-{4-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-1-ol;
2-Methyl-2-{4-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propionitrile;
2-Fluoro-4-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
(6-Methoxy-5-trifluoromethyl-pyridin-2-yl)-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid;
2-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-{2-Fluoro-4-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
2-Methyl-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propionic acid;
5-Chloro-6-[2-piperidin-1-yl-4-(4-trifluoromethyl-phenylamino)-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepin-7-yl]-nicotinic acid methyl ester;
{5-Chloro-6-[2-piperidin-1-yl-4-(4-trifluoromethyl-phenylamino)-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepin-7-yl]-pyridin-3-yl}-methanol;
N2,N2-Dimethyl-N6-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
2-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-N-methyl-isobutyramide;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(piperazine-1-sulfonyl)-phenyl]-amine;
(4-Methanesulfonyl-phenyl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(2-Amino-1,1-dimethyl-ethyl)-phenyl]-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethanesulfonyl-phenyl)-amine;
1,1,1-Trifluoro-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
2-{2-Fluoro-4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
2-Methyl-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-1-ol;
[4-(2-Amino-1,1-dimethyl-ethyl)-phenyl]-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N6-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-N2-methyl-3-trifluoromethyl-pyridine-2,6-diamine;
2-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
N6-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine;
2-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
(3-Fluoro-4-trifluoromethyl-phenyl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methyl ester;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(morpholine-4-sulfonyl)-phenyl]-amine;
1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid dimethylamide;
[4-(2-Dimethylamino-1,1-dimethyl-ethyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
N6-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethoxy-phenyl)-amine;
[4-(1,1-Dimethyl-2-methylamino-ethyl)-phenyl]-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-Bromo-phenyl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-Chloro-phenyl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(1-Methyl-1,2,3,4-tetrahydro-quinolin-7-yl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(1,4,4-trimethyl-1,2,3,4-tetrahydro-quinolin-7-yl)-amine;
2-Methyl-2-{4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propionitrile;
4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid;
N2-Methyl-N6-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
2-Fluoro-4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
2-Fluoro-4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid 1-{4-(2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanol;
[4-(2-Dimethylamino-1,1-dimethyl-ethyl)-phenyl]-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N,N-Dimethyl-2-{4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methyl ester;
(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid;
(1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropyl)-methanol;
[4-(1-Dimethylaminomethyl-cyclopropyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(1-Aminomethyl-cyclopropyl)-phenyl]-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid amide;
1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methylamide;
N-Methyl-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
N,N-Dimethyl-2-{4-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
[4-(2-Dimethylamino-1,1-dimethyl-ethyl)-phenyl]-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(1,1-Dimethyl-2-methylamino-ethyl)-phenyl]-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N6-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
N2-Methyl-N6-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
N2,N2-Dimethyl-N6-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(piperazine-1-sulfonyl)-phenyl]-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(morpholine-4-sulfonyl)-phenyl]-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(piperazine-1-sulfonyl)-phenyl]-amine;
[4-(Morpholine-4-sulfonyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(Piperazine-1-sulfonyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N6-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-N2,N2-dimethyl-3-trifluoromethyl-pyridine-2,6-diamine;
N6-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
[4-(1-Methylaminomethyl-cyclopropyl)-phenyl]-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
N2-Methyl-N6-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
N2,N2-Dimethyl-N6-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-3-trifluoromethyl-pyridine-2,6-diamine;
1,1,1-Trifluoro-2-{4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
[4-(2-Amino-1,1-dimethyl-ethyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyrazin-2-yl)-amine;
(6-Methoxy-5-trifluoromethyl-pyridin-2-yl)-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-{2-Fluoro-4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
2-Fluoro-4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid;
2-Fluoro-4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
(3-Fluoro-4-trifluoromethyl-phenyl)-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
N-Methyl-2-{4-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
N,N-Dimethyl-2-{4-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
2-{2-Fluoro-4-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-2-ol;
2-Fluoro-4-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid;
2-Fluoro-4-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-benzoic acid methyl ester;
2-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-N,N-dimethyl-isobutyramide;
N-Methyl-2-{4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-isobutyramide;
(6-Methoxy-5-trifluoromethyl-pyridin-2-yl)-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-Bromo-phenyl)-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethoxy-phenyl)-amine;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethoxy-phenyl)-amine;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(5-trifluoromethyl-pyrazin-2-yl)-amine;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methylamide;
1-{4-[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanol;
1-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid amide;
(4-Bromo-phenyl)-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(4-Methanesulfonyl-phenyl)-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
(1-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropyl)-methanol;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethanesulfonyl-phenyl)-amine;
[4-(2-Dimethylamino-1,1-dimethyl-ethyl)-phenyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(1,1-Dimethyl-2-methylamino-ethyl)-phenyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(2-Amino-1,1-dimethyl-ethyl)-phenyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
2-Methyl-2-{4-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-propan-1-ol;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid;
[4-(1,1-Dimethyl-2-methylamino-ethyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methylamide;
[4-(1-Methylaminomethyl-cyclopropyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(1-Aminomethyl-cyclopropyl)-phenyl]-[2-piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(1-Aminomethyl-cyclopropyl)-phenyl]-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[4-(1-Dimethylaminomethyl-cyclopropyl)-phenyl]-[2-(2-methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid dimethylamide;
1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid amide;
1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methyl ester;
1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid;
[2-Morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(pyrrolidine-1-sulfonyl)-phenyl]-amine;
(1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropyl)-methanol;
1-{4-[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanol;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(1,4,4-trimethyl-1,2,3,4-tetrahydro-quinolin-7-yl)-amine;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(1-methyl-1,2,3,4-tetrahydro-quinolin-7-yl)-amine;
[2-(2-Methyl-pyrrolidin-1-yl)-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(6-trifluoromethyl-pyridin-3-yl)-amine;
[4-(1-Aminomethyl-cyclopropyl)-phenyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-[4-(1-methylaminomethyl-cyclopropyl)-phenyl]-amine;
[4-(1-Dimethylaminomethyl-cyclopropyl)-phenyl]-[2-isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid dimethylamide;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid amide;
(1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropyl)-methanol;
1-{4-[2-Isopropyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanol;
1-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methyl ester;
[4-(Morpholine-4-sulfonyl)-phenyl]-[2-morpholin-4-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-amine;
1-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid;
1-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid methylamide; and
1-{4-[2-Piperidin-1-yl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ylamino]-phenyl}-cyclopropanecarboxylic acid dimethylamide;
and pharmaceutically acceptable salts thereof.
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103. A pharmaceutical composition for treating a disease, disorder, or medical condition mediated by TRPV1 activity, comprising:
-
(a) an effective amount of an agent selected from the group consisting of compounds of Formula (I);
wherein;
R1 is —
H;
—
NRaRb;
—
OH;
a —
C1-6alkyl, —
OC1-6alkyl, —
O-(saturated monocyclic cycloalkyl), —
OC1alkyl-(saturated monocyclic cycloalkyl), —
O-(saturated monocyclic heterocycloalkyl), —
O-phenyl, —
O-benzyl, —
S—
C1-6alkyl, —
S-(saturated monocyclic cycloalkyl), —
SC1alkyl-(saturated monocyclic cycloalkyl), —
S-(saturated monocyclic heterocycloalkyl), —
S-phenyl, —
S-benzyl, or —
SO2—
C1-6alkyl group unsubstituted or substituted with one or two moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, and halo substituents;
or a phenyl, monocyclic cycloalkyl, or monocyclic heteroaryl group unsubstituted or substituted with a —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent;
where Ra and Rb are each independently —
H;
—
C1-6alkyl;
a —
C2-3alkyl group substituted with a —
OH, —
OC1-4alkyl, —
NRcRd, or halo substituent;
or a saturated monocyclic cycloalkyl, —
C1alkyl-(saturated monocyclic cycloalkyl), saturated monocyclic heterocycloalkyl, —
C1alkyl-(saturated monocyclic heterocycloalkyl), phenyl, benzyl, or —
C1alkyl-(monocyclic heteroaryl) group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, and halo substituents;
or
Ra and Rb taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl or bridged bicyclic heterocycloalkyl group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
C-4alkyl-OH, —
C1-2alkyl-OC1-2alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, halo, —
CO2H, and benzyl substituents;
where Rc and Rd are each independently —
H or —
C1-6alkyl;
or Rc and Rd taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Rp and Rq are each independently —
H or —
C1-6alkyl;
or Rp and Rq taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Re and Rf are each independently —
H or —
C1-6alkyl;
or Re and Rf taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
R2 is —
H or —
C1-6alkyl;
R3 is a monocyclic cycloalkyl, phenyl, benzyl, phenethyl, indanyl, thiazolyl, thiophenyl, pyridyl, pyridylmethyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, or tetrahydroisoquinolinyl group unsubstituted or substituted with one, two, or three Rg substituents;
where each Rg substituent is —
C1-6alkyl;
—
C1-4alkyl-OH unsubstituted or substituted with —
CF3;
saturated monocyclic cycloalkyl;
—
OH;
—
OC1-6alkyl;
phenoxy;
—
CN;
—
NO2;
—
N(Rh)Ri;
—
C1-4alkyl-N(Rh)Ri;
—
C(O)N(Rh)Ri;
—
N(Rh)C(O)Ri;
—
N(Rh)SO2C1-6alkyl;
—
C(O)C1-6alkyl;
—
S(O)0-2—
C1-6alkyl;
—
SO2CF3;
—
SO2N(Rh)Ri;
—
SCF3;
halo;
—
CF3;
—
OCF3;
—
CO2H;
—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CN;
—
C(Rj)(Rx)—
OH;
—
C(Rj)(Rx)—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CO2H;
—
C(Rj)(Rx)—
C(O)N(Rh)Ri;
phenyl;
ormonocyclic heteroaryl;
ortwo adjacent Rg substituents taken together form —
OC1-2alkylO—
;
where Rh and Ri are each independently —
H or —
C1-6alkyl;
or Rh and Ri (when both are present) taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl group;
Rj is independently —
H, —
C1-6alkyl, or —
CF3;
Rx is —
H or —
C1-6alkyl;
or Rj and Rx taken together with the carbon to which they are attached form a monocyclic cycloalkyl ring;
andAr is a phenyl, pyridyl, imidazolyl, pyrimidinyl, pyridazinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one, two, or three Rk substituents;
where each Rk substituent is independently —
C1-6alkyl, —
C1-2alkyl-OH, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, halo, —
CF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl;
ortwo adjacent Rk substituents taken together form —
OC1-2alkylO—
;
where Rl and Rm are each independently —
H, —
C1-6alkyl, saturated monocyclic cycloalkyl, or —
CF3;
and pharmaceutically acceptable salts, pharmaceutically acceptable prodrugs, and pharmaceutically active metabolites thereof; and
(b) a pharmaceutically acceptable excipient. - View Dependent Claims (104, 105, 106, 107)
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108. A method of treating a subject suffering from or diagnosed with a disease, disorder, or medical condition mediated by TRPV1 activity, comprising administering to the subject in need of such treatment an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically active metabolite of such compound:
-
wherein;
R1 is —
H;
—
NRaRb;
—
OH;
a —
C1-6alkyl, —
OC1-6alkyl, —
O-(saturated monocyclic cycloalkyl), —
OC1alkyl-(saturated monocyclic cycloalkyl), —
O-(saturated monocyclic heterocycloalkyl), —
O-phenyl, —
O-benzyl, —
S—
C1-6alkyl, —
S-(saturated monocyclic cycloalkyl), —
SC1alkyl-(saturated monocyclic cycloalkyl), —
S-(saturated monocyclic heterocycloalkyl), —
S-phenyl, —
S-benzyl, or —
SO2—
C1-6alkyl group unsubstituted or substituted with one or two moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, and halo substituents;
or a phenyl, monocyclic cycloalkyl, or monocyclic heteroaryl group unsubstituted or substituted with a —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NReRf, or halo substituent;
where Ra and Rb are each independently —
H;
—
C1-6alkyl;
a —
C2-3alkyl group substituted with a —
OH, —
OC1-4alkyl, —
NRcRd, or halo substituent;
or a saturated monocyclic cycloalkyl, —
C1alkyl-(saturated monocyclic cycloalkyl), saturated monocyclic heterocycloalkyl, —
C1alkyl-(saturated monocyclic heterocycloalkyl), phenyl, benzyl, or —
C1alkyl-(monocyclic heteroaryl) group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, and halo substituents;
or
Ra and Rb taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl or bridged bicyclic heterocycloalkyl group unsubstituted or substituted with one, two, or three moieties independently selected from the group consisting of —
C1-6alkyl, —
C1-4alkyl-OH, —
C1-2alkyl-OC1-2alkyl, —
OH, —
OC1-4alkyl, —
NRpRq, halo, —
CO2H, and benzyl substituents;
where Rc and Rd are each independently —
H or —
C1-6alkyl;
or Rc and Rd taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Rp and Rq are each independently —
H or —
C1-6alkyl;
or Rp and Rq taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
where Re and Rf are each independently —
H or —
C1-6alkyl;
or Re and Rf taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl;
R2 is —
H or —
C1-6alkyl;
R3 is a monocyclic cycloalkyl, phenyl, benzyl, phenethyl, indanyl, thiazolyl, thiophenyl, pyridyl, pyridylmethyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, or tetrahydroisoquinolinyl group unsubstituted or substituted with one, two, or three Rg substituents;
where each Rg substituent is —
C1-6alkyl;
—
C1-4alkyl-OH unsubstituted or substituted with —
CF3;
saturated monocyclic cycloalkyl;
—
OH;
—
OC1-6alkyl;
phenoxy;
—
CN;
—
NO2;
—
N(Rh)Ri;
—
C1-4alkyl-N(Rh)Ri;
—
C(O)N(Rh)Ri;
—
N(Rh)C(O)Ri;
—
N(Rh)SO2C1-6alkyl;
—
C(O)C1-6alkyl;
—
S(O)0-2—
C1-6alkyl;
—
SO2CF3;
—
SO2N(Rh)Ri;
—
SCF3;
halo;
—
CF3;
—
OCF3;
—
CO2H;
—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CN;
—
C(Rj)(Rx)—
OH;
—
C(Rj)(Rx)—
CO2C1-6alkyl;
—
C(Rj)(Rx)—
CO2H;
—
C(Rj)(Rx)—
C(O)N(Rh)Ri;
phenyl;
ormonocyclic heteroaryl;
ortwo adjacent Rg substituents taken together form —
OC1-2alkylO—
;
where Rh and Ri are each independently —
H or —
C1-6alkyl;
or Rh and Ri (when both are present) taken together with their nitrogen of attachment form a saturated monocyclic heterocycloalkyl group;
Rj is independently —
H, —
C1-6alkyl, or —
CF3;
Rx is —
H or —
C1-6alkyl;
or Rj and Rx taken together with the carbon to which they are attached form a monocyclic cycloalkyl ring;
and Ar is a phenyl, pyridyl, imidazolyl, pyrimidinyl, pyridazinyl, or fused-bicyclic heteroaryl group unsubstituted or substituted with one, two, or three Rk substituents;
where each Rk substituent is independently —
C1-6alkyl, —
C1-2alkyl-OH, —
OH, —
OC1-6alkyl, phenoxy, —
CN, —
NO2, —
N(Rl)Rm, —
C(O)N(Rl)Rm, —
N(Rl)C(O)Rm, —
N(Rl)SO2C1-6alkyl, —
N(Rl)SO2CF3, —
C(O)C1-6alkyl, —
S(O)0-2—
C1-6alkyl, —
SO2CF3, —
SO2N(Rl)Rm, —
SCF3, halo, —
CF3, —
OCF3, —
CO2H, or —
CO2C1-6alkyl;
ortwo adjacent Rk substituents taken together form —
OC1-2alkylO—
;
where Rl and Rm are each independently —
H, —
C1-6alkyl, saturated monocyclic cycloalkyl, or —
CF3.- View Dependent Claims (109, 110, 111, 112, 113, 114, 115)
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Specification