Inhibitors of akt activity
First Claim
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1. A compound of Formula (I):
- wherein;
A is selected from;
nitrogen, —
C-halogen and —
CH;
L1 is selected from the group consisting of a bond, —
O—
, —
N(R5)—
, —
S—
, —
S(O)—
, —
S(O2)—
, alkyl, and —
N(R5)C(O)—
;
L2 is selected from the group consisting of a bond, —
O—
, heterocycle, —
N(R5)—
, —
N(R5)C(O)—
, —
S—
, —
S(O)—
, —
S(O2)—
, and —
C(O)N(R5)—
;
L3 is alkyl, wherein the alkyl is optionally substituted with one or two substituents independently selected from the group consisting of amino, methylamino, dimethylamino, oxo, and hydroxy;
L6 is selected from the group consisting of a bond, —
O—
, —
N(R5)—
, —
S—
, —
S(O)—
, —
S(O2)—
, alkyl, and —
N(R5)C(O)—
;
R1 is selected from the group consisting of aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heterocycle and substituted heterocycle;
R2 is selected from alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocycle, substituted heterocycle, and a cyclic or polycyclic aromatic ring containing from 3 to 16 carbon atoms and optionally containing one or more heteroatoms, provided that when the number of carbon atoms is 3 the aromatic ring contains at least two heteroatoms and when the number of carbon atoms is 4 the aromatic ring contains at least one heteroatom, and optionally substituted with one or more substituents selected from the group consisting of;
alkyl, substituted alkyl, trifluoroalkoxy, C1-C12aryl, aryloxy, —
O(CH2)qR31, —
NHC(O)—
NHR41, —
C(O)R43, substituted cycloalkyl, substituted C1-C12aryl, heterocycle, substituted heterocycle, oxo, hydroxy, alkoxy, cycloalkyl, acyloxy, amino, N-acylamino, nitro, cyano, halogen, —
C(O)OR7, —
C(O)NR8R9, —
S(O)2NR8R9, and —
S(O)nR7, where n is 0-2, q is 1-6, R7 is hydrogen, alkyl, cycloalkyl, C1-C12aryl, substituted alkyl, substituted cycloalkyl and substituted C1-C12aryl, R31 is C1-C12aryl, cycloalkyl and heterocycle, each of which is optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, acyloxy, amino, methylamino, dimethylamino, N-acylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl, R41 is selected from hydrogen, C1-C12aryl, cycloalkyl and heterocycle, wherein C1-C12aryl, cycloalkyl and heterocycle are optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, amino, methylamino, dimethylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl, R43 is selected from C1-C12aryl, cycloalkyl and heterocycle, each of which is optionally substituted with from 1 to 4 substituents selected from;
halogen, hydroxyalkyl, alkoxy, amino, methylamino, dimethylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl, and R8 and R9 are independently hydrogen, cycloalkyl, C1-C12aryl, substituted cycloalkyl, substituted C1-C12aryl, alkyl or alkyl substituted with one or more substituents selected from the group consisting of;
alkoxy, acyloxy, aryloxy, amino, N-acylamino, oxo, hydroxy, —
C(O)OR10, —
S(O)nR10, —
C(O)NR10R11, —
S(O)2NR10R11, nitro, cyano, cycloalkyl, substituted cycloalkyl, halogen, aryl, and substituted aryl, or R8 and R9 taken together with the nitrogen to which they are attached represent a 5 to 6 member saturated ring containing up to one other heteroatom selected from oxygen and nitrogen, where the ring is optionally subtituted with one or more substituents selected from amino, methylamino and dimethylamino, where R10 and R11 are independently hydrogen, alkyl, cycloalkyl, C1-C12aryl, substituted alkyl, substituted cycloalkyl and substituted C1-C12aryl, and n is 0-2, and when L6 is a bond, R2 can additionally be halogen;
R3 and R6 are independently selected from the group consisting of hydrogen, amino, methylamino, dimethylamino, aryl, substituted aryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, —
S—
C1-C12aryl, —
O—
C1-C12aryl, —
OalkylC1-C12aryl, aryloxy, substituted aryloxy and arylalkoxy; and
R4 is selected from the group consisting of hydrogen and halogen;
where R5 is selected from the group consisting of hydrogen, —
S(O)2CH3, —
S(O)2H and alkyl;
provided that when, R1 is azaindazole, substituted azaindazole, 1H-thienopyrazole, substituted 1H-thienopyrazole, benzamide, substituted benzamide, phenylethanone, substituted phenylethanone, thiophene, substituted thiophene, furan or substituted furan, R2 may additionally be hydrogen;
further provided that when R1 is isoquinoline, R2 is not furyl or alkyl.
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Accused Products
Abstract
Invented are novel pyridine compounds, the use of such compounds as inhibitors of PKB/AKT kinase activity and in the treatment of cancer and arthritis.
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Citations
47 Claims
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1. A compound of Formula (I):
-
wherein;
A is selected from;
nitrogen, —
C-halogen and —
CH;
L1 is selected from the group consisting of a bond, —
O—
, —
N(R5)—
, —
S—
, —
S(O)—
, —
S(O2)—
, alkyl, and —
N(R5)C(O)—
;
L2 is selected from the group consisting of a bond, —
O—
, heterocycle, —
N(R5)—
, —
N(R5)C(O)—
, —
S—
, —
S(O)—
, —
S(O2)—
, and —
C(O)N(R5)—
;
L3 is alkyl, wherein the alkyl is optionally substituted with one or two substituents independently selected from the group consisting of amino, methylamino, dimethylamino, oxo, and hydroxy;
L6 is selected from the group consisting of a bond, —
O—
, —
N(R5)—
, —
S—
, —
S(O)—
, —
S(O2)—
, alkyl, and —
N(R5)C(O)—
;
R1 is selected from the group consisting of aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heterocycle and substituted heterocycle;
R2 is selected from alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocycle, substituted heterocycle, and a cyclic or polycyclic aromatic ring containing from 3 to 16 carbon atoms and optionally containing one or more heteroatoms, provided that when the number of carbon atoms is 3 the aromatic ring contains at least two heteroatoms and when the number of carbon atoms is 4 the aromatic ring contains at least one heteroatom, and optionally substituted with one or more substituents selected from the group consisting of;
alkyl, substituted alkyl, trifluoroalkoxy, C1-C12aryl, aryloxy, —
O(CH2)qR31, —
NHC(O)—
NHR41, —
C(O)R43, substituted cycloalkyl, substituted C1-C12aryl, heterocycle, substituted heterocycle, oxo, hydroxy, alkoxy, cycloalkyl, acyloxy, amino, N-acylamino, nitro, cyano, halogen, —
C(O)OR7, —
C(O)NR8R9, —
S(O)2NR8R9, and —
S(O)nR7,where n is 0-2, q is 1-6, R7 is hydrogen, alkyl, cycloalkyl, C1-C12aryl, substituted alkyl, substituted cycloalkyl and substituted C1-C12aryl, R31 is C1-C12aryl, cycloalkyl and heterocycle, each of which is optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, acyloxy, amino, methylamino, dimethylamino, N-acylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl,R41 is selected from hydrogen, C1-C12aryl, cycloalkyl and heterocycle, wherein C1-C12aryl, cycloalkyl and heterocycle are optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, amino, methylamino, dimethylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl,R43 is selected from C1-C12aryl, cycloalkyl and heterocycle, each of which is optionally substituted with from 1 to 4 substituents selected from;
halogen, hydroxyalkyl, alkoxy, amino, methylamino, dimethylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl, andR8 and R9 are independently hydrogen, cycloalkyl, C1-C12aryl, substituted cycloalkyl, substituted C1-C12aryl, alkyl or alkyl substituted with one or more substituents selected from the group consisting of;
alkoxy, acyloxy, aryloxy, amino, N-acylamino, oxo, hydroxy, —
C(O)OR10, —
S(O)nR10, —
C(O)NR10R11, —
S(O)2NR10R11, nitro, cyano, cycloalkyl, substituted cycloalkyl, halogen, aryl, and substituted aryl,or R8 and R9 taken together with the nitrogen to which they are attached represent a 5 to 6 member saturated ring containing up to one other heteroatom selected from oxygen and nitrogen, where the ring is optionally subtituted with one or more substituents selected from amino, methylamino and dimethylamino, where R10 and R11 are independently hydrogen, alkyl, cycloalkyl, C1-C12aryl, substituted alkyl, substituted cycloalkyl and substituted C1-C12aryl, and n is 0-2, and when L6 is a bond, R2 can additionally be halogen;
R3 and R6 are independently selected from the group consisting of hydrogen, amino, methylamino, dimethylamino, aryl, substituted aryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, —
S—
C1-C12aryl, —
O—
C1-C12aryl, —
OalkylC1-C12aryl, aryloxy, substituted aryloxy and arylalkoxy; and
R4 is selected from the group consisting of hydrogen and halogen;
where R5 is selected from the group consisting of hydrogen, —
S(O)2CH3, —
S(O)2H and alkyl;
provided that when, R1 is azaindazole, substituted azaindazole, 1H-thienopyrazole, substituted 1H-thienopyrazole, benzamide, substituted benzamide, phenylethanone, substituted phenylethanone, thiophene, substituted thiophene, furan or substituted furan, R2 may additionally be hydrogen;
further provided that when R1 is isoquinoline, R2 is not furyl or alkyl. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 43, 44, 45, 46)
L1 is selected from the group consisting of a bond, —
O—
, —
N(R5)—
, —
S—
, —
S(O)—
, —
S(O2)—
, alkyl, and —
N(R5)C(O)—
;
L2 is selected from the group consisting of a bond, —
O—
, heterocycle, —
N(R5)—
, —
N(R5)C(O)—
, —
S—
, —
S(O)—
, —
S(O2)—
, and —
C(O)N(R5)—
;
L3 is alkyl, wherein the alkyl is optionally substituted with one or two substituents independently selected from the group consisting of amino, methylamino, dimethylamino, oxo, and hydroxy;
L6 is a bond;
R1 is selected from the group consisting of C1-C12aryl and substituted C1-C12aryl;
R2 is selected from alkyl, substituted alkyl, halogen, cycloalkyl, substituted cycloalkyl, heterocycle, substituted heterocycle, and C1-C12aryl optionally substituted with one or more substituents selected from the group consisting of;
alkyl, substituted alkyl, trifluoroalkoxy, C1-C12aryl, aryloxy, —
O(CH2)qR31, —
NHC(O)—
NHR41, —
C(O)R43, hydroxy, alkoxy, cycloalkyl, N-acylamino, nitro and halogen,where q is 1-6, R31 is C1-C12aryl, cycloalkyl and heterocycle, each of which is optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, acyloxy, amino, methylamino, dimethylamino, N-acylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl,R41 is selected from hydrogen, C1-C12aryl, cycloalkyl and heterocycle, wherein C1-C12aryl, cycloalkyl and heterocycle are optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, amino, methylamino, dimethylamino, hydroxy, nitro, tetrazole, cyano, oxo and trifluoromethyl,R43 is selected from C1-C12aryl, cycloalkyl and heterocycle, each of which is optionally substituted with from 1 to 4 substituents selected from;
halogen, hydroxyalkyl, alkoxy, amino, methylamino, dimethylamino, hydroxyl, nitro, tetrazole, cyano, oxo and trifluoromethyl,R3 and R6 are independently selected from the group consisting of hydrogen, amino, methylamino, dimethylamino, aryl, substituted aryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, —
S—
C1-C12aryl, aryloxy and arylalkoxy; and
R4 is selected from the group consisting of hydrogen and halogen;
where R5 is selected from the group consisting of hydrogen, —
S(O)2CH3, —
S(O)2H and alkyl;
provided that when, R1 is azaindazole, substituted azaindazole, 1H-thienopyrazole, substituted 1H-thienopyrazole, benzamide, substituted benzamide, phenylethanone, substituted phenylethanone, thiophene, substituted thiophene, furan or substituted furan, R2 may additionally be hydrogen;
further provided that when R1 is isoquinoline, R2 is not furyl or alkyl.
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4. A pharmaceutically acceptable salt, hydrate, solvate or pro-drug of a compound of Formula (I), as described in claim 3.
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5. A compound of claim 1 represented by the following Formula (II):
-
wherein;
A is selected from nitrogen, —
CF and —
CH;
L4 is selected from the group consisting of a bond, heterocycle, —
O—
, and —
NH—
;
L5 is alkyl, wherein the alkyl is optionally substituted with one or two substituents independently selected from the group consisting of amino, oxo, and hydroxy;
R14 is selected from the group consisting of C1-C12aryl, and substituted C1-C12aryl;
R15 is selected from alkyl, substituted alkyl, halogen, cycloalkyl, substituted cycloalkyl, heterocycle, substituted heterocycle, C1-C12aryl and C1-C12aryl optionally substituted with one or more substituents selected from the group consisting of;
alkyl, substituted alkyl, trifluoroalkoxy, aryloxy, —
O(CH2)qR31, —
NHC(O)—
NHR41, —
C(O)R43, hydroxy, alkoxy, acyloxy, amino, cycloalkyl, N-acylamino, nitro, cyano and halogen,where q is 1-6, R31 is C1-C12aryl optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, and hydroxy,R41 is selected from hydrogen and C1-C12aryl optionally substituted with from 1 to 4 substituents selected from;
halogen, alkyl, hydroxyalkyl, alkoxy, and hydroxy,R43 is C1-C12aryl substituted with from 1 to 4 substituents selected from;
halogen, hydroxyalkyl, alkoxy, and hydroxy, andR16 and R17 are independently selected from the group consisting of hydrogen, C1-C12aryl, substituted C1-C12aryl, heterocycle, cycloalkyl, —
S—
C1-C12aryl, and C1-C12arylalkoxy;
provided that when, R14 is azaindazole, substituted azaindazole, 1H-thienopyrazole, substituted 1H-thienopyrazole, benzamide, substituted benzamide, phenylethanone, substituted phenylethanone, 2-pyridinecarboxamide, substituted 2-pyridinecarboxamide, (methylsulfonyl)benzene, substituted (methylsulfonyl)benzene, thiophene, substituted thiophene, furan or substituted furan, R15 may additionally be hydrogen;
further provided that when R14 is isoquinoline, R15 is not furyl or alkyl.
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6. A pharmaceutically acceptable salt, hydrate, solvate or pro-drug of a compound of Formula (II), as described in claim 5.
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7. A compound of Formula (II), as described in claim 5:
wherein A is selected from nitrogen, —
CF and —
CH;
L4 is selected from the group consisting of a bond, —
O—
, and —
NH—
;
L5 is alkyl, wherein the alkyl is substituted with one or two substituents independently selected from the group consisting of amino, oxo, and hydroxy;
R14 is selected from phenyl, pyridine, indazole, 7-azaindole, quinoline, isoquinoline, substituted phenyl, substituted pyridine, substituted indazole, substituted 7-azaindole, substituted quinoline and substituted isoquinoline;
R15 is selected from cycloalkyl, substituted cycloalkyl, phenyl, pyridine, thiophene, furan, pyrrole, indazole, quinoline, isoquinoline, 7-azaindole, substituted phenyl, substituted pyridine, substituted thiophene, substituted furan, substituted indazole, substituted quinoline, substituted 7-azaindole and substituted isoquinoline; and
R16 and R17 are independently selected from the group consisting of hydrogen, indole, substituted indole, azaindole, substituted azaindole, naphthalene, substituted naphthalene, benzofuran, substituted benzofuran, phenyl, pyridine, thiophene, furan, pyrrole, substituted phenyl, substituted pyridine, substituted thiophene, substituted furan, and substituted pyrrole;
provided that when, R14 is 7-azaindazole, 4-azaindazole, 1H-thieno[3,2-c]pyrazole, benzamide, 1-phenylethanone, 2-furancarboxamide, 1-(2-furanyl)ethanone, 2-thienylcarboxamide, 1-(2-thienyl)ethanone, substituted 7-azaindazole, substituted 4-azaindazole, substituted 1H-thieno[3,2-c]pyrazole, substituted benzamide, substituted 1-phenylethanone, substituted 2-furancarboxamide, substituted 1-(2-furanyl)ethanone, substituted 2-thienylcarboxamide or substituted 1-(2-thienyl)ethanone, 2-pyridinecarboxamide, substituted 2-pyridinecarboxamide, (methylsulfonyl)benzene, substituted (methylsulfonyl)benzene, R15 may additionally be hydrogen;
further provided that when R14 is isoquinoline, R15 is not furyl or alkyl.
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8. A pharmaceutically acceptable salt, hydrate, solvate or pro-drug of a compound of Formula (II), as described in claim 7.
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9. A compound of claim 1 selected from:
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(S)-1-Benzyl-2-[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-furan-2-yl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[5,6-bis-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-thiophen-2-yl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-(4-chlorophenyl)-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-(3-chlorophenyl)-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]ethylamine;
(S)-1-Benzyl-2-[6-benzyl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-cyclopent-1-enyl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-cyclopentyl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-cyclohex-1-enyl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[6-cyclohexyl-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy]-ethylamine;
3-Methyl-5-[2-phenyl-5-(piperidin-4-ylmethoxy)-pyridin-3-yl]-1H-indazole;
3-[5-(3-Methyl-1H-indazol-5-yl)-6-phenyl-pyridin-3-yloxy}-propylamine;
(S)-1-Benzyl-2-[5-(3-methyl-1H-indazol-5-yl)-6-(5-methyl-thiophen-2-yl)-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-[5-(3-methyl-1H-indazol-5-yl)-6-(5-methyl-furan-2-yl)-pyridin-3-yloxy]-ethylamine;
3-Methyl-5-[2-phenyl-5-(4-pyridin-3-yl-methyl-piperazin-1-yl)-pyridin-3-yl]-1H-indazole;
3-Methyl-5-[2-phenyl-5-(4-pyridin-4-ylmethyl-piperazin-1-yl)-pyridin-3-yl]-1H-indazole;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(5-chloro-2-thienyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(3-aminophenyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
(S)-1-Benzyl-2-[5-(1H-indazol-5-yl)-6-phenyl-pyridin-3-yloxy]-ethylamine;
(S)-1-Benzyl-2-{6-[3-(3-fluoro-benzyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-pyridin-3-yloxy}-ethylamine;
(S)-1-Benzyl-2-[5-(3-phenyl-1H-indazol-5-yl)-6-phenyl-pyridin-3-yloxy]-ethylamine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
N-{3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenyl}benzamide;
N-{3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenyl}-2,6-difluorobenzamide;
N-{3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenyl}cyclohexanecarboxamide;
[(1S)-2-({5-[3-(2-furanyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
{(1S)-2-phenyl-1-[({6-phenyl-5-[3-(2-thienyl)-1H-indazol-5-yl]-3-pyridinyl}oxy)methyl]ethyl}amine;
[(1S)-2-({5-[3-(3-furanyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-[3-(3-thienyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
[(1S)-2-{[5-(2,3-dimethyl-2H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-cyclopropyl-1H-indazol-5-yl)-6-(3-furanyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(1-methyl-1H-pyrazol-4-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-{1-[(3-fluorophenyl)methyl]-1H-pyrazol-4-yl}-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
((1S)-2-phenyl-1-{[(6-phenyl-5-{3-[5-(1-piperazinylmethyl)-2-furanyl]-1H-indazol-5-yl}-3-pyridinyl)oxy]methyl}ethyl)amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(2-furanyl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-(3-methyl-1H-indazol-5-yl)-6-[3-(phenyloxy)phenyl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
3-[({5-[5-(5-{[(2S)-2-amino-3-phenylpropyl]oxy}-2-phenyl-3-pyridinyl)-1H-indazol-3-yl]-2-furanyl}methyl)amino]propanenitrile;
[(1S)-2-({6-(2-furanyl)-5-[3-(2-furanyl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
{5-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-2-thienyl}methanol;
{(1S)-2-phenyl-1-[({6-phenyl-5-[3-(phenylmethyl)-1H-indazol-5-yl]-3-pyridinyl}oxy)methyl]ethyl}amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(1-methyl-1H-pyrrol-2-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
5-(5-{[(2S)-2-amino-3-phenylpropyl]oxy}-2-phenyl-3-pyridinyl)-1H-indazol-3-amine;
[(1S)-2-({5-[3-(1-methylethenyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrazol-4-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
(2S)-N,N-dimethyl-1-{[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-3-phenyl-2-propanamine;
[(1S)-2-{[3-(3-methyl-1H-indazol-5-yl)-2,4′
-bipyridin-5-yl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[3-(3-methyl-1H-indazol-5-yl)-2,3′
-bipyridin-5-yl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-iodo-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-[(5-(3-methyl-1H-indazol-5-yl)-6-{3-[(trifluoromethyl)oxy]phenyl}-3-pyridinyl)oxy]-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(3,5-dimethyl-4-isoxazolyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
4-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
2-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
[(1S)-2-{[6-[3-(ethyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-(3-methyl-1H-indazol-5-yl)-6-[3-(methyloxy)phenyl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
{3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenyl}(phenyl)methanone;
[(1S)-2-{[6-{3-[(1-methylethyl)oxy]phenyl}-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-[3-(2-furanyl)-1H-indazol-5-yl]-6-(1H-pyrrol-2-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(2-{[(3-fluorophenyl)methyl]oxy}phenyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{(6-(4-{[(3-fluorophenyl)methyl]oxy}phenyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-[3-(5-chloro-2-thienyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-[3-(4-methyl-2-thienyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-[3-(5-methyl-2-furanyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-[3-(5-methyl-2-thienyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-ethenyl-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
{(1S)-2-phenyl-1-[({6-phenyl-5-[3-(1H-pyrrol-2-yl)-1H-indazol-5-yl]-3-pyridinyl}oxy)methyl]ethyl}amine;
[(1S)-2-(1H-indol-3-yl)-1-({[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}methyl)ethyl]amine;
5-(3-methyl-1H-indazol-5-yl)-6-phenyl-N-(3-phenylpropyl)-3-pyridinamine;
5-(3-methyl-1H-indazol-5-yl)-6-phenyl-N-(3-phenylbutyl)-3-pyridinamine;
[(2S)-2-amino-3-phenylpropyl][5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]amine;
[(2S)-2-amino-3-phenylpropyl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
((1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amine;
N-[(2S)-2-amino-3-phenylpropyl]-N-[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]methanesulfonamide;
5-(3-methyl-1H-indazol-5-yl)-N-[2-methyl-2-(phenylthio)propyl]-6-phenyl-3-pyridinamine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
((1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-1-{[(phenylmethyl)oxy]methyl}ethyl)amine;
(2S)-2-amino-3-{[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-1-propanol;
5-(3-methyl-1H-indazol-5-yl)-6-phenyl-N-[(2S)-2-pyrrolidinylmethyl]-3-pyridinamine;
((2S)-2-amino-3-{4-[(phenylmethyl)oxy]phenyl}propyl)[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]amine;
[(2S)-2-amino-3-phenylpropyl][5-(1H-indazol-5-yl)-6-phenyl-3-pyridinyl]amine;
[(2S)-2-amino-3-phenylpropyl][6-(3-furanyl)-5-(1H-indazol-5-yl)-3-pyridinyl]amine;
[(2S)-2-amino-3-phenylpropyl][5-(1H-indazol-5-yl)-6-(3-thienyl)-3-pyridinyl]amine;
2-[5-{[(2S)-2-amino-3-phenylpropyl]amino}-3-(1H-indazol-5-yl)-2-pyridinyl]phenol;
2-[5-{[(2S)-2-amino-3-phenylpropyl]amino}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
[(2S)-2-amino-3-phenylpropyl][5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]amine;
[(2S)-2-amino-3-phenylpropyl][5-(3-methyl-1H-indazol-5-yl)-6-(5-methyl-2-thienyl)-3-pyridinyl]amine;
[(2R)-2-amino-3-phenylpropyl][5-(1H-indazol-5-yl)-6-(3-thienyl)-3-pyridinyl]amine;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
[(1S)-2-(1H-indol-3-yl)-1-({[5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-(1H-indol-3-yl)-1-({[5-(3-methyl-1H-indazol-5-yl)-6-(5-methyl-2-thienyl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-{[6-ethyl-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-ethenyl-1H-indazol-5-yl)-6-(3-furanyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-ethyl-1H-indazol-5-yl)-6-(3-furanyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(3-pyridinyl)-1H-indazol-5-yl]-3-pyridinyl]oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-methyl-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-(3-methyl-1H-indazol-5-yl)-6-[2-(methyloxy)phenyl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-[2-(ethyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-[5-chloro-2-(methyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-[5-fluoro-2-(propyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({5-[3-(1-methylethyl)-1H-indazol-5-yl]-6-phenyl-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-(3-furanyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
N-[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]-L-phenylalaninamide;
N-[6-(2-hydroxyphenyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]-L-phenylalaninamide;
2-[5-{([(2S)-2-amino-3-(1-benzothien-3-yl)propyl]oxy}-3-(1H-indazol-5-yl)-2-pyridinyl]phenol;
[(1S)-2-(1-benzothien-3-yl)-1-({[6-(2-furanyl)-5-(1H-indazol-5-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-1-(2-naphthalenylmethyl)ethyl]amine;
N-[5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]-L-phenylalaninamide;
[(2S)-2-amino-3-(1H-indol-3-yl)propyl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
(2S)-1-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-3-phenyl-2-propanol;
1-{3-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]phenyl}ethanone;
[(1S)-2-{[6-cyclopentyl-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-(1-benzothien-3-yl)-1-({[5-(1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-(1-benzothien-3-yl)-1-({[6-(3-furanyl)-5-(1H-indazol-5-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-(1-benzothien-3-yl)-1-({[5-(1H-indazol-5-yl)-6-(3-thienyl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-(1-benzothien-3-yl)-1-({[5-(1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-{[5-(1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-1-(1H-pyrazol-1-ylmethyl)ethyl]amine;
[(1S)-2-(1-benzothien-3-yl)-1-({[5-(1H-indazol-5-yl)-6-(5-methyl-2-thienyl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
5-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-2-(3-furanyl)-3-pyridinyl]-N-4-pyridinyl-1H-indazol-3-amine;
N-{5-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-2-(3-furanyl)-3-pyridinyl]-1H-indazol-3-yl}benzamide;
(1E)-1-{3-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]phenyl}ethanone oxime;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)propyl]amine;
(2S)-N-methyl-1-{[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}-3-phenyl-2-propanamine;
[(1S)-2-{[6-[5-fluoro-2-(methyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-[3,5-difluoro-2-(methyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(4-pyridinyl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
2-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4-fluorophenol;
2-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4,6-difluorophenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(6-fluoro-3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-ethyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
[(1S)-2-{[5-(3-ethyl-1H-indazol-5-yl)-6-(3-furanyl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-ethyl-1H-indazol-5-yl)-6-(2-furanyl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-ethyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(1H-pyrrol-2-yl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-((6-(3-furanyl)-5-[3-(1H-pyrazol-4-yl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-([5-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-(2-furanyl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-{[5-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-{[5-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-(3-furanyl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-{[6-(1-benzothien-2-yl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(1-benzofuran-2-yl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)-1-(1H-indol-3-ylmethyl)ethyl]amine;
5-[5-{[(2S)-2-(1-azetidinyl)-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]-3-methyl-1H-indazole;
[(1S)-2-({6-(3-furanyl)-5-[3-(1H-pyrazol-4-yl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(1H-indol-3-ylmethyl)ethyl]amine;
3-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furyl)pyridin-3-yl]benzamide;
4-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furyl)pyridin-3-yl]benzamide;
5-(5-{[(2S)-3-(1H-indol-3-yl)-2-(1-piperidinyl)propyl]oxy}-2-phenyl-3-pyridinyl)-3-methyl-1H-indazole;
5-(2-(3-furanyl)-5-{[(2S)-3-(1H-indol-3-yl)-2-(4-morpholinyl)propyl]oxy}-3-pyridinyl)-3-methyl-1H-indazole;
[(1S)-2-({6-(3-furanyl)-5-[3-(1H-pyrazol-4-yl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]dimethylamine;
(3S)-3-({[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}methyl)-2-methyl-2,3,4,9-tetrahydro-1H-carboline;
1-{5-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]-2-thienyl}ethanone;
(2S)-1-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-3-(1H-indol-3-yl)-N-methyl-2-propanamine;
5-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]-N,N-dimethyl-2-furancarboxamide;
5-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]-N-methyl-2-furancarboxamide;
5-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3-pyridinyl]-2-furancarboxamide;
[(2S)-2-amino-3-phenylpropyl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]methylamine;
[(1S)-2-(3,4-dichlorophenyl)-1-({[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]oxy}methyl)ethyl]amine;
N-[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]-L-phenylalaninamide;
N-[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-3-pyridinyl]-L-phenylalaninamide;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]amino}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4-fluorophenol;
((1S)-3-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-({[4-(trifluoromethyl)phenyl]methyl}propyl)amine;
[(1S)-3-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)propyl]amine;
{(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-[(5-methyl-1H-indol-3-yl)methyl]ethyl}amine;
[(1S)-2-(1H-indol-3-yl)-1-({[5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-3-yl)pyridin-3-yl]oxy}methyl)ethyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-(1H-indol-3-yl)-1-({[5-(3-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
5-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-2-(3-furanyl)-3-pyridinyl]-1H-indazole-3-carboxamide;
5-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-2-(3-furanyl)-3-pyridinyl]-1H-indazole-3-carbonitrile;
(2S)-1-{[6-(2-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-3-(1H-indol-3-yl)-2-propanamine;
2-[5-{[(2S)-2-amino-3-(1-benzothien-3-yl)-3-propyl]oxy}-3-(1H-indazol-5-yl)-2-pyridinyl]-4-flurophenol;
2-[5-{[(2S)-2-amino-3-(1-benzothien-3-yl)-3-propyl]oxy}-3-(1H-indazol-5-yl)-2-pyridinyl]-4,6-diflurophenol;
[(1S)-2-(1-benzothien-3-yl)-1-({[5,6-bis(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-(1-benzothien-3-yl)-1-({[4-(3-furanyl)-3-(3-methyl-1H-indazol-5-yl)phenyl]oxy}methyl)ethyl]amine;
4′
-{[(2S)-2-amino-3-(1-benzothien-3-yl)propyl]oxy}-3,5-difluoro-2′
-(3-methyl-1H-indazol-5-yl)-2-biphenylol;
4′
-{[(2S)-2-amino-3-(1-benzothien-3-yl)propyl]oxy}-5-fluoro-2′
-(3-methyl-1H-indazol-5-yl)-2-biphenylol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4,6-difluorophenol;
[(2S)-2-amino-3-(1H-indol-3-yl)propyl][5-(3-methyl-1H-indazol-5-yl)-6-(1H-pyrrol-2-yl)-3-pyridinyl]amine;
[(2S)-2-amino-3-(1H-indol-3-yl)propyl][6-[5-fluoro-2-(methyloxy)phenyl]-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]amino}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
2-[5-([(2S)-2-amino-3-(1H-indol-3-yl)propyl]amino}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenol;
[(2S)-2-amino-3-(5-fluoro-1H-indol-3-yl)propyl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
[(2S)-2-amino-4-pentyn-1-yl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
[(2S)-2-amino-3-(5,6,7-trifluoro-1H-indol-3-yl)propyl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
[(2S)-2-amino-3-(5,7-difluoro-1H-indol-3-yl)propyl][6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(1H-pyrrolo[2,3-b]pyridin-2-ylmethyl)ethyl]amine;
[(2R)-2-amino-3-phenylpropyl][3-fluoro-4-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)phenyl]amine;
[(2R)-2-amino-3-(1H-indol-3-yl)propyl][3-fluoro-4-(3-furanyl)-5-(3-methyl-1H-indazol-5-yl)phenyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
[(1S)-2-(1H-indol-3-yl)-1-({[6-(2-methyl-3-furanyl)-5-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-(1H-indol-3-yl)-1-({[5-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-6-phenyl-3-pyridinyl]oxy}methyl)ethyl]amine;
[(1S)-2-{[6-(3-furanyl)-5-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]methylamine;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-2-pyridinyl]phenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-2-pyridinyl]-6-fluorophenol;
[(1S)-2-{[5-[3-(3,5-dimethyl-4-isoxazolyl)-1H-indazol-5-yl]-6-(3-furanyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-({6-(3-furanyl)-5-[3-(2-pyridinyl)-1H-indazol-5-yl]-3-pyridinyl}oxy)-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(2-chlorophenyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(2-methylphenyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[6-(2-fluorophenyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
2-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4-chlorophenol;
[(1S)-2-{[6-(1-benzothien-3-yl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]benzamide;
3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]benzonitrile;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(3-nitrophenyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(4-methyl-2-thienyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
N-{3-[5-{[(2S)-2-amino-3-phenylpropyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenyl}-N′
-phenylurea;
[(1S)-2-{[5-(3-methyl-1H-indazol-5-yl)-6-(2-thienyl)-3-pyridinyl]oxy}-1-(phenylmethyl)ethyl]amine;
[(1S)-2-(1H-indol-3-yl)-1-({[6-(2-methyl-3-furanyl)-5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy}methyl)ethyl]amine;
{2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]phenyl]amine;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-6-fluorophenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4-chlorophenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-indazol-5-yl)-2-pyridinyl]-4-fluorophenol;
[(1S)-2-{[6-[3,5-difluoro-2-(methyloxy)phenyl]-5-(3-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-3-pyridinyl]oxy}-1-(1H-indol-3-ylmethyl)ethyl]amine;
2-[5-([(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-2-pyridinyl]-4,6-difluorophenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-2-pyridinyl]phenol;
2-[5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-(3-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-2-pyridinyl]-4-chlorophenol;
3-(5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-pyridinyl)benzamide;
1-[3-(5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-3-pyridinyl)phenyl]ethanone; and
5-{[(2S)-2-amino-3-(1H-indol-3-yl)propyl]oxy}-2-(3-furanyl)-3,4′
-bipyridine-2′
-carboxamide.
-
-
10. A pharmaceutically acceptable salt, hydrate, solvate or pro-drug of a compound of Formula (II), as described in claim 9.
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11. A pharmaceutical composition comprising a compound according to claim 1, and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof and a pharmaceutically acceptable carrier.
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12. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound of Formula (I) as described in claim 1 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof, which process comprises bringing the compound of Formula (I) and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof into association with a pharmaceutically acceptable carrier or diluent.
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13. A method of treating or lessening the severity of cancer in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula I, as described in claim 1 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof.
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14. The method of claim 13 wherein the mammal is a human.
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15. A method of treating or lessening the severity of cancer in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula II, as described in claim 5 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof.
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16. The method of claim 15 wherein the mammal is a human.
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17. The method according to claim 13 wherein said cancer is selected from brain (gliomas), glioblastomas, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, breast, colon, head and neck, kidney, lung, liver, melanoma, ovarian, pancreatic, prostate, sarcoma and thyroid.
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18. The method according to claim 15 wherein said cancer is selected from brain (gliomas), glioblastomas, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, breast, colon, head and neck, kidney, lung, liver, melanoma, ovarian, pancreatic, prostate, sarcoma and thyroid.
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20. The method of inhibiting Akt activity in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula I, as described in claim 1 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof.
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21. The method of claim 20 wherein the mammal is a human.
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22. A method of treating cancer in a mammal in need thereof, which comprises:
- administering to such mammal a therapeutically effective amount of
a) a compound of Formula (I), as described in claim 1 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof; and
b) at least one anti-neoplastic agent.
- administering to such mammal a therapeutically effective amount of
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23. The method claim 22, wherein the at least one anti-neoplastic agent is selected from the group consisting essentially of anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormonal analogues, signal transduction pathway inhibitors;
- non-receptor tyrosine kinase angiogenesis inhibitors;
immunotherapeutic agents;
proapoptotic agents; and
cell cycle signaling inhibitors.
- non-receptor tyrosine kinase angiogenesis inhibitors;
-
24. The method of claim 22, wherein the at least one anti-neoplastic agent is an anti-microtubule agent selected from diterpenoids and vinca alkaloids.
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25. The method of claim 22, wherein the at least one anti-neoplastic agent is a diterpenoid.
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26. The method of claim 22, wherein the at least one anti-neoplastic agent is a vinca alkaloid.
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27. The method of claim 22, wherein the at least one anti-neoplastic agent is a platinum coordination complex.
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28. The method of claim 22, wherein the at least one anti-neoplastic agent is paclitaxel, carboplatin, or vinorelbine.
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29. The method of claim 22, wherein the at least one anti-neoplastic agent is paclitaxel.
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30. The method of claim 22, wherein the at least one anti-neoplastic agent is carboplatin.
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31. The method of claim 22, wherein the at least one anti-neoplastic agent is vinorelbine.
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32. The method of claim 22, wherein the at least one anti-neoplatic agent is a signal transduction pathway inhibitor.
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33. The method of claim 32, wherein the signal transduction pathway inhibitor is an inhibitor of a growth factor receptor kinase selected from the group consisting of VEGFR2, TIE2, PDGFR, BTK, IGFR-1, TrkA, TrkB, TrkC, and c-fms.
-
34. The method of claim 32, wherein the signal transduction pathway inhibitor is an inhibitor of a serine/threonine kinase selected from the group consisting of rafk, akt, and PKC-zeta.
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35. The method of claim 32, wherein the signal transduction pathway inhibitor is an inhibitor of a serine/threonine kinase selected from the src family of kinases.
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36. The method of claim 35, wherein the signal transduction pathway inhibitor is an inhibitor of c-src.
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37. The method of claim 32, wherein the signal transduction pathway inhibitor is an inhibitor of Ras oncogene selected from inhibitors of farnesyl transferase and geranylgeranyl transferase.
-
38. The method of claim 32, wherein the signal transduction pathway inhibitor is an inhibitor of a serine/threonine kinase selected from the group consisting of PI3K.
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39. The method of claim 22, wherein the at least one anti-neoplastic agent is a cell cycle signaling inhibitor.
-
40. The method of claim 39, wherein the cell cycle signaling inhibitor is selected from inhibitors of the group CDK2, CDK4, and CDK6.
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43. A method of treating or lessening the severity of arthritis in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula I, as described in claim 1 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof.
-
44. The method of claim 43 wherein the mammal is a human.
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45. A method of treating or lessening the severity of arthritis in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula II, as described in claim 5 and/or a pharmaceutically acceptable salt, hydrate, solvate or pro-drug thereof.
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46. The method of claim 45 wherein the mammal is a human.
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19. (canceled)
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41-42. -42. (canceled)
-
47. (canceled)
Specification