1N-alkyl-n-arylpyrimidinamines and derivatives thereof
First Claim
Patent Images
1. A compound of formula (I):
-
or a pharmaceutically acceptable salt thereof, wherein;
R1 is independently selected, at each occurrence from the group consisting of C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, and C1-C2 haloalkyl;
R3 is C1-C4 alkyl, C3-C6 cycloalkyl, C1-C2 haloalkyl, nitro, NR6R7, OR8, S(O)nR8, C(═
O)R9, C(═
O)NR6R7, C(═
S)NR6R7, —
(CHR16)kNR6R7, (CH2)kOR8, C(═
O)NR10CH(R11)CO2R12, —
C(OH)(R25)(R25a), —
(CH2)pS(O)n-alkyl, —
(CHR16)R25, —
C(CN)(R25)(R16), —
C(═
O)R25, —
CH(CO2R16)2, NR10C(═
O)CH(R11)NR10R12, NR10CH(R11)CO2R12;
K and L are each independently CX′
;
R2 is independently selected at each occurrence from the group consisting of hydrogen, halo, halomethyl, C1-C3 alkyl, and cyano;
R4 is (CH2)mOR16, C1-C4 alkyl, allyl, propargyl, (CH2)mR13, or —
(CH2)mOC(O)R16;
X is halogen, S(O)2R8, SR8, halomethyl, —
(CH2)pOR8, cyano, —
(CHR16)pNR14R15, —
C(═
O)R8, C1-C6 alkyl, C4-C10 cycloalkylalkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C3-C6 cycloalkyl, nitro, thio-(C1-C10)-alkyl, —
C(═
NOR16)—
C1-C4-alkyl, —
C(═
NOR16)H, or —
C(═
O)NR14R15 where substitution by R18 can occur on any carbon containing substituents;
X′
is independently selected at each occurrence from the group consisting of hydrogen, halogen, S(O)nR8, halomethyl, —
(CHR16)pOR8, cyano, —
(CHR16)pNR14R15, C(═
O)R8, C1-C6 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C3-C6 cycloalkyl, nitro, thio-(C1-C10)-alkyl, —
C(═
NOR16)—
C1-C4-alkyl, —
C(═
NOR16)H, or —
C(═
O)NR14R15 where substitution by R18 can occur on any carbon containing substituents;
R5 is halo, —
C(═
NOR16)—
C1-C4-alkyl, C1-C6 alkyl, C1-C3 haloalkyl, C1-C6 alkoxy, —
(CHR16)pOR8, (CHR16)pS(O)nR8, —
(CHR16)pNR14R15, C3-C6 cycloalkyl, C2-C10 alkenyl, C2-C10 alkynyl, cyano, C3-C6 cycloalkoxy, nitro, amino-(C2-C10)-alkyl, thio-(C2-C10)-alkyl, SOn(R8), C(═
O)R8, —
C(═
NOR16)H, or C(═
O)NR14R15, where substitution by R18 can occur on any carbon containing substituents;
R6 and R7 are independently selected at each occurrence from the group consisting of hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C6 alkoxy, (C4-C12)-cycloalkylalkyl, —
(CH2)kR13, (CHR16)pOR8, —
(C1-C6 alkyl)-aryl, phenyl, heteroaryl, —
S(O)z-aryl or —
(C1-C6 alkyl)-heteroaryl, wherein the aryl or heteroaryl groups are optionally substituted with 1-3 groups selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, amino, NHC(═
O)(C1-C6 alkyl), NH(C1-C6 alkyl), N(C1-C6 alkyl)2, nitro, carboxy, CO2(C1-C6 alkyl), cyano, S(O)z—
(C1-C6 alkyl);
or can be taken together to form —
(CH2)qA(CH2)r—
, optionally substituted with 0-3 R17;
A is CH2, O, NR25, C(═
O), S(O)n, N(C(═
O)R17), N(R19), C(H)(NR14R15), C(H)(OR20), C(H)(C(═
O)R21), N(S(O)nR21);
R8 is independently selected at each occurrence from the group consisting of hydrogen;
C1-C6 alkyl;
—
(C4-C12) cycloalkylalkyl;
(CH2)tR22;
C3-C10 cycloalkyl;
—
NR6R7;
aryl;
heteroaryl;
—
NR16(CH2)nNR6R7;
—
(CH2)kR25; and
(CH2)theteroaryl or (CH2)taryl, either of which can be optionally substituted with 1-3 groups selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, amino, NHC(═
O)(C1-C6 alkyl), NH(C1-C6 alkyl) N(C1-C6 alkyl)2, nitro, carboxy, CO2(C1-C6 alkyl), cyano, and S(O)z(C1-C6-alkyl);
R9 is independently selected at each occurrence from R10, hydroxy, C1-C4 alkoxy, C3-C6 cycloalkyl, C2-C4 alkenyl, phenyl substituted with 0-3 R18, and —
(C1-C6 alkyl)-aryl substituted with 0-3 R18;
R10, R16, R23, and R24 are independently selected at each occurrence from hydrogen or C1-C4 alkyl;
R11 is C1-C4 alkyl substituted with 0-3 groups chosen from the following;
keto, amino, sulfhydryl, hydroxyl, guanidinyl, p-hydroxyphenyl, imidazolyl, phenyl, indolyl, and indolinyl, or, when taken together with an adjacent R10, are (CH2)t;
R12 is hydrogen or an appropriate amine protecting group for nitrogen or an appropriate carboxylic acid protecting group for carboxyl;
R13 is independently selected at each occurrence from the group consisting of CN, OR19, SR19, and C3-C6 cycloalkyl;
R14 and R15 are independently selected at each occurrence from the group consisting of hydrogen, C4-C10 cycloalkyl-alkyl, and R19;
R17 is independently selected at each occurrence from the group consisting of R10, C1-C4 alkoxy, halo, OR23, SR23, NR23R24, and (C1-C6) alkyl (C1-C4) alkoxy;
R18 is independently selected at each occurrence from the group consisting of R10, hydroxy, halogen, C1-C2 haloalkyl, C1-C4 alkoxy, C(═
O)R24, and cyano;
R19 is independently selected at each occurrence from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, (CH2)wR22, and phenyl substituted with 0-3 R18;
R20 is independently selected at each occurrence from the group consisting of R10, C(═
O)R31, and C2-C4 alkenyl;
R21 is independently selected at each occurrence from the group consisting of R10, C1-C4 alkoxy, NR23R24, and hydroxyl;
R22 is independently selected at each occurrence from the group consisting of cyano, OR24, SR24, NR23R24, C1-C6 alkyl, C3-C6 cycloalkyl, —
S(O)nR31, and —
C(═
O)R25;
R25, which can be optionally substituted with 0-3 R17, is independently selected at each occurrence from the group consisting of phenyl, and pyridyl;
R25a, which can be optionally substituted with 0-3 R17, is independently selected at each occurrence from the group consisting of H and R25;
R27 is independently selected at each occurrence from the group consisting of C1C3 alkyl, C2-C4 alkenyl, C2-4 alkynl, C2-4 alkoxy, aryl, nitro, cyano, halogen, and phenyloxy;
R31 is independently selected at each occurrence from the group consisting of C1-C4 alkyl, C3-C7 cycloalkyl, C4-C10 cycloalkyl-alkyl, and aryl-(C1-C4) alkyl;
k, m, and r are independently selected at each occurrence from 1-4;
n is independently selected at each occurrence from 0-2;
p, q, and z are independently selected at each occurrence from 0-3;
t and w are independently selected at each occurrence from 1-6;
provided that when K and L are both CH, then (A) when R2 is H and R1 and R3 are methyl, (1) and R4 is methyl, then (a) R5 can not be C1-C6 alkyl when X is OH and X′
is H;
(b) R5 can not be (CHR16)pNR14R15 wherein p is 0 when X and X′
are —
OCH3; and
(c) R5 can not be (CHR 16)pNR14R15 when X and X′
are —
OCH2CH3; and
(2) and R4 is ethyl, then (a) R5 can not be (CHR16)pNR14R15 when X and X′
are —
OCH3;
(b) R5 can not be (CHR16)pOR18 with p=0 and R18=H when X is Br and X′
is OH; and
(c) R5 can not be C1-C6 alkyl substituted with OH;
or (CHR16)pNR14R15 wherein R16=H and p=1-3 and R14 and R15 are H or C1-C6 alkyl when X is —
SCH3 and X′
is H;
(B) when R2 is H, R4 is ethyl, R5 is iso-propyl, X is Br, X′
is H, and (1) R1 is CH3;
then (a) R3 can not be OR8, CO2R12, C(═
O)NR6R7, (CH2)kOR8;
(CHR16)kNR6R7;
(2) R1 is —
CH2CH2CH3 then R3 can not be C1-C6 alkyl;
further provided that when X′
is H, and K and L are both CH, then (D) when R2 is H or C1-C3 alkyl;
R4 is C1-C4 alkyl;
R5, X and/or X′
are OH, halo, CF3, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, cyano, amino, carbamoyl, or C1-C4 alkanoyl; and
R1 is C1-C4 alkyl, then R3 can not be —
NH(substituted phenyl) or —
N (C1-C4 alkyl) (substituted phenyl) and further provided that when R3 is S(O)nR8, R8 is not hydrogen;
and when R3 is —
C(CN)(R25)(R16), R25 is not pyridyl and when R3 is S(O)nR8, R8 is not H;
wherein the term “
heterocycle”
is defined as pyridyl, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl or benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl or octahydroisoquinolinyl, azocinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, thiophenyl, thianthrenyl, furanyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, 2H-pyrrolyl, pyrrole, imidazolyl, pyrazolyl, isothiazolyl, isoxazole, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindole, 3H-indolyl, indolyl, 1H-indazolyl, purinyl, 4H-quinolizinyl, isoquinolinyl, quinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β
-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl or oxazolidinyl;
wherein the term “
aryl”
is defined as phenyl, biphenyl or naphthyl; and
wherein the term “
heteroaryl”
is defined as 2-, or 3-, or 4-pyridyl;
2- or 3-furyl;
2- or 3-benzofuranyl;
2-, or 3-thiophenyl;
2- or 3-benzo[b]thiophenyl;
2-, or 3-, or 4-quinolinyl;
1-, or 3-, or 4-isoquinolinyl;
2- or 3-pyrrolyl;
1- or 2- or 3-indolyl;
2-, or 4-, or 5-oxazolyl;
2-benzoxazolyl;
2- or 4- or 5-imidazolyl;
1- or 2-benzimidazolyl;
2- or 4- or 5-thiazolyl;
2-benzothiazolyl;
3- or 4- or 5-isoxazolyl;
3- or 4- or 5-pyrazolyl;
3- or 4- or 5-isothiazolyl;
3- or 4-pyridazinyl;
2- or 4- or 5-pyrimidinyl;
2-pyrazinyl;
2-triazinyl;
3- or 4- cinnolinyl;
1-phthalazinyl;
2- or 4-quinazolinyl;
or 2-quinoxalinyl ring.
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Abstract
The present invention provides novel compounds, compounds and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsy, irritable bowel syndrome, immune suppression, Alzheimer'"'"'disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula:
wherein R1, R3, R4, R5, Z, Y, V, X, X′, J, K, L, and M are as defined herein.
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Citations
7 Claims
-
1. A compound of formula (I):
-
or a pharmaceutically acceptable salt thereof, wherein; R1 is independently selected, at each occurrence from the group consisting of C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, and C1-C2 haloalkyl;
R3 is C1-C4 alkyl, C3-C6 cycloalkyl, C1-C2 haloalkyl, nitro, NR6R7, OR8, S(O)nR8, C(═
O)R9, C(═
O)NR6R7, C(═
S)NR6R7, —
(CHR16)kNR6R7, (CH2)kOR8, C(═
O)NR10CH(R11)CO2R12, —
C(OH)(R25)(R25a), —
(CH2)pS(O)n-alkyl, —
(CHR16)R25, —
C(CN)(R25)(R16), —
C(═
O)R25, —
CH(CO2R16)2, NR10C(═
O)CH(R11)NR10R12, NR10CH(R11)CO2R12;
K and L are each independently CX′
;
R2 is independently selected at each occurrence from the group consisting of hydrogen, halo, halomethyl, C1-C3 alkyl, and cyano;
R4 is (CH2)mOR16, C1-C4 alkyl, allyl, propargyl, (CH2)mR13, or —
(CH2)mOC(O)R16;
X is halogen, S(O)2R8, SR8, halomethyl, —
(CH2)pOR8, cyano, —
(CHR16)pNR14R15, —
C(═
O)R8, C1-C6 alkyl, C4-C10 cycloalkylalkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C3-C6 cycloalkyl, nitro, thio-(C1-C10)-alkyl, —
C(═
NOR16)—
C1-C4-alkyl, —
C(═
NOR16)H, or —
C(═
O)NR14R15 where substitution by R18 can occur on any carbon containing substituents;
X′
is independently selected at each occurrence from the group consisting of hydrogen, halogen, S(O)nR8, halomethyl, —
(CHR16)pOR8, cyano, —
(CHR16)pNR14R15, C(═
O)R8, C1-C6 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C3-C6 cycloalkyl, nitro, thio-(C1-C10)-alkyl, —
C(═
NOR16)—
C1-C4-alkyl, —
C(═
NOR16)H, or —
C(═
O)NR14R15 where substitution by R18 can occur on any carbon containing substituents;
R5 is halo, —
C(═
NOR16)—
C1-C4-alkyl, C1-C6 alkyl, C1-C3 haloalkyl, C1-C6 alkoxy, —
(CHR16)pOR8, (CHR16)pS(O)nR8, —
(CHR16)pNR14R15, C3-C6 cycloalkyl, C2-C10 alkenyl, C2-C10 alkynyl, cyano, C3-C6 cycloalkoxy, nitro, amino-(C2-C10)-alkyl, thio-(C2-C10)-alkyl, SOn(R8), C(═
O)R8, —
C(═
NOR16)H, or C(═
O)NR14R15, where substitution by R18 can occur on any carbon containing substituents;
R6 and R7 are independently selected at each occurrence from the group consisting of hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C6 alkoxy, (C4-C12)-cycloalkylalkyl, —
(CH2)kR13, (CHR16)pOR8, —
(C1-C6 alkyl)-aryl, phenyl, heteroaryl, —
S(O)z-aryl or —
(C1-C6 alkyl)-heteroaryl, wherein the aryl or heteroaryl groups are optionally substituted with 1-3 groups selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, amino, NHC(═
O)(C1-C6 alkyl), NH(C1-C6 alkyl), N(C1-C6 alkyl)2, nitro, carboxy, CO2(C1-C6 alkyl), cyano, S(O)z—
(C1-C6 alkyl);
or can be taken together to form —
(CH2)qA(CH2)r—
, optionally substituted with 0-3 R17;
A is CH2, O, NR25, C(═
O), S(O)n, N(C(═
O)R17), N(R19), C(H)(NR14R15), C(H)(OR20), C(H)(C(═
O)R21), N(S(O)nR21);
R8 is independently selected at each occurrence from the group consisting of hydrogen;
C1-C6 alkyl;
—
(C4-C12) cycloalkylalkyl;
(CH2)tR22;
C3-C10 cycloalkyl;
—
NR6R7;
aryl;
heteroaryl;
—
NR16(CH2)nNR6R7;
—
(CH2)kR25; and
(CH2)theteroaryl or (CH2)taryl, either of which can be optionally substituted with 1-3 groups selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, amino, NHC(═
O)(C1-C6 alkyl), NH(C1-C6 alkyl) N(C1-C6 alkyl)2, nitro, carboxy, CO2(C1-C6 alkyl), cyano, and S(O)z(C1-C6-alkyl);
R9 is independently selected at each occurrence from R10, hydroxy, C1-C4 alkoxy, C3-C6 cycloalkyl, C2-C4 alkenyl, phenyl substituted with 0-3 R18, and —
(C1-C6 alkyl)-aryl substituted with 0-3 R18;
R10, R16, R23, and R24 are independently selected at each occurrence from hydrogen or C1-C4 alkyl;
R11 is C1-C4 alkyl substituted with 0-3 groups chosen from the following;
keto, amino, sulfhydryl, hydroxyl, guanidinyl, p-hydroxyphenyl, imidazolyl, phenyl, indolyl, and indolinyl, or, when taken together with an adjacent R10, are (CH2)t;
R12 is hydrogen or an appropriate amine protecting group for nitrogen or an appropriate carboxylic acid protecting group for carboxyl;
R13 is independently selected at each occurrence from the group consisting of CN, OR19, SR19, and C3-C6 cycloalkyl;
R14 and R15 are independently selected at each occurrence from the group consisting of hydrogen, C4-C10 cycloalkyl-alkyl, and R19;
R17 is independently selected at each occurrence from the group consisting of R10, C1-C4 alkoxy, halo, OR23, SR23, NR23R24, and (C1-C6) alkyl (C1-C4) alkoxy;
R18 is independently selected at each occurrence from the group consisting of R10, hydroxy, halogen, C1-C2 haloalkyl, C1-C4 alkoxy, C(═
O)R24, and cyano;
R19 is independently selected at each occurrence from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, (CH2)wR22, and phenyl substituted with 0-3 R18;
R20 is independently selected at each occurrence from the group consisting of R10, C(═
O)R31, and C2-C4 alkenyl;
R21 is independently selected at each occurrence from the group consisting of R10, C1-C4 alkoxy, NR23R24, and hydroxyl;
R22 is independently selected at each occurrence from the group consisting of cyano, OR24, SR24, NR23R24, C1-C6 alkyl, C3-C6 cycloalkyl, —
S(O)nR31, and —
C(═
O)R25;
R25, which can be optionally substituted with 0-3 R17, is independently selected at each occurrence from the group consisting of phenyl, and pyridyl;
R25a, which can be optionally substituted with 0-3 R17, is independently selected at each occurrence from the group consisting of H and R25;
R27 is independently selected at each occurrence from the group consisting of C1C3 alkyl, C2-C4 alkenyl, C2-4 alkynl, C2-4 alkoxy, aryl, nitro, cyano, halogen, and phenyloxy;
R31 is independently selected at each occurrence from the group consisting of C1-C4 alkyl, C3-C7 cycloalkyl, C4-C10 cycloalkyl-alkyl, and aryl-(C1-C4) alkyl;
k, m, and r are independently selected at each occurrence from 1-4;
n is independently selected at each occurrence from 0-2;
p, q, and z are independently selected at each occurrence from 0-3;
t and w are independently selected at each occurrence from 1-6;
provided that when K and L are both CH, then(A) when R2 is H and R1 and R3 are methyl, (1) and R4 is methyl, then (a) R5 can not be C1-C6 alkyl when X is OH and X′
is H;
(b) R5 can not be (CHR16)pNR14R15 wherein p is 0 when X and X′
are —
OCH3; and
(c) R5 can not be (CHR 16)pNR14R15 when X and X′
are —
OCH2CH3; and
(2) and R4 is ethyl, then (a) R5 can not be (CHR16)pNR14R15 when X and X′
are —
OCH3;
(b) R5 can not be (CHR16)pOR18 with p=0 and R18=H when X is Br and X′
is OH; and
(c) R5 can not be C1-C6 alkyl substituted with OH;
or (CHR16)pNR14R15 wherein R16=H and p=1-3 and R14 and R15 are H or C1-C6 alkyl when X is —
SCH3 and X′
is H;
(B) when R2 is H, R4 is ethyl, R5 is iso-propyl, X is Br, X′
is H, and(1) R1 is CH3;
then(a) R3 can not be OR8, CO2R12, C(═
O)NR6R7, (CH2)kOR8;
(CHR16)kNR6R7;
(2) R1 is —
CH2CH2CH3 then R3 can not be C1-C6 alkyl;
further provided that when X′
is H, and K and L are both CH, then(D) when R2 is H or C1-C3 alkyl;
R4 is C1-C4 alkyl;
R5, X and/or X′
are OH, halo, CF3, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, cyano, amino, carbamoyl, or C1-C4 alkanoyl; and
R1 is C1-C4 alkyl, then R3 can not be —
NH(substituted phenyl) or —
N (C1-C4 alkyl) (substituted phenyl) and further provided that when R3 is S(O)nR8, R8 is not hydrogen;
and when R3 is —
C(CN)(R25)(R16), R25 is not pyridyl and when R3 is S(O)nR8, R8 is not H;
wherein the term “
heterocycle”
is defined as pyridyl, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl or benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl or octahydroisoquinolinyl, azocinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, thiophenyl, thianthrenyl, furanyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, 2H-pyrrolyl, pyrrole, imidazolyl, pyrazolyl, isothiazolyl, isoxazole, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindole, 3H-indolyl, indolyl, 1H-indazolyl, purinyl, 4H-quinolizinyl, isoquinolinyl, quinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β
-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl or oxazolidinyl;
wherein the term “
aryl”
is defined as phenyl, biphenyl or naphthyl; and
wherein the term “
heteroaryl”
is defined as 2-, or 3-, or 4-pyridyl;
2- or 3-furyl;
2- or 3-benzofuranyl;
2-, or 3-thiophenyl;
2- or 3-benzo[b]thiophenyl;
2-, or 3-, or 4-quinolinyl;
1-, or 3-, or 4-isoquinolinyl;
2- or 3-pyrrolyl;
1- or 2- or 3-indolyl;
2-, or 4-, or 5-oxazolyl;
2-benzoxazolyl;
2- or 4- or 5-imidazolyl;
1- or 2-benzimidazolyl;
2- or 4- or 5-thiazolyl;
2-benzothiazolyl;
3- or 4- or 5-isoxazolyl;
3- or 4- or 5-pyrazolyl;
3- or 4- or 5-isothiazolyl;
3- or 4-pyridazinyl;
2- or 4- or 5-pyrimidinyl;
2-pyrazinyl;
2-triazinyl;
3- or 4- cinnolinyl;
1-phthalazinyl;
2- or 4-quinazolinyl;
or 2-quinoxalinyl ring.- View Dependent Claims (2, 3, 4, 5, 6, 7)
R1 is C1-C4 alkyl;
R3 is C1-C4 alkyl, C3-C6 cycloalkyl, C1-C2 haloalkyl, NR6R7, OR8, C(═
O)R9, C(═
O)NR6R7, —
(CHR16)kNR6R7, (CH2)kOR8, —
(CHR16)R25, substituted C1-C4 alkyl, substituted C1-C4 alkenyl, substituted C2-C4 alkynyl, substituted C1-C4 alkoxy, substituted C3-C6 cycloalkyl or substituted C1-C4 alkylamino, where substitution by one or two R27 can occur on any carbon-containing substituent;
R4 is C1-C4 alkyl, allyl, or propargyl;
X is halogen, S(O)2R8, SR8, halomethyl, —
(CH2)pOR8, cyano, —
(CHR16)pNR14R15, —
C(═
O)R8, C1-C6 alkyl, C4-C10 cycloalkylalkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, aryl-(C2-C10)-alkyl, C3-C6 cycloalkyl, aryl-(C1-C10)-alkoxy, nitro, thio-(C1-C10)-alkyl, —
C(═
NOR16)—
C1-C4-alkyl, —
C(═
NOR16)H, or —
C(═
O)NR14R15;
X′
is independently selected at each occurrence from the group consisting of hydrogen, halogen except when M is N, S(O)nR8, halomethyl, —
(CHR16)pOR8, cyano, —
(CHR16)pNR14R15, C(═
O)R8, C1-C6 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, aryl-(C1-C10)-alkyl, C3-C6 cycloalkyl, aryl-(C1-C10)-alkoxy, nitro, thio-(C1-C10)-alkyl, —
C(═
NOR16)—
C1-C4-alkyl, —
C(═
NOR16)H, or —
C(═
O)NR14R15;
R5 is halo, —
C(═
NOR16)—
C1-C4-alkyl, C1-C6 alkyl, C1-C3 haloalkyl, C1-C6 alkoxy, —
(CHR16)pOR8, (CHR16)pS(O)nR8, —
(CHR16)pNR14R15, C3-C6 cycloalkyl, C2-C10 alkenyl, C2-C10 alkynyl, cyano, C3-C6 cycloalkoxy, nitro, amino-(C2-C10)-alkyl, thio-(C2-C10)-alkyl, SOn(R8), C(═
O)R8, —
C(═
NOR16)H, or C(═
O)NR14R15;
R6 and R7 are independently selected at each occurrence from the group consisting of hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C6 alkoxy, (C4-C12)-cycloalkylalkyl, —
(CH2)kR13, (CHR16)pOR8, phenyl, or —
S(O)z-aryl;
or can be taken together to form —
(CH2)qA(CH2)r—
, optionally substituted with 0-3 R17;
R8 is independently selected at each occurrence from the group consisting of hydrogen;
C1-C6 alkyl;
—
(C4-C12) cycloalkylalkyl;
(CH2)tR22;
C3-C10 cycloalkyl;
or —
NR6R7; and
R9 is independently selected at each occurrence from R10, C1-C4 alkoxy, C3-C6 cycloalkyl, or C2-C4 alkenyl.
-
-
3. A compound of claim 1 selected from the group consisting of:
-
N-(2,4-dimethoxyphenyl)-N-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromophenyl)-N-allyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-dimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-dibromophenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-ethylphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-tert-butylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-tert-butylphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-trifluoromethylphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-trifluoromethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4,6-trimethoxyphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4,6-trimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-allyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-propyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-cyclohexylethyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-diethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-ethyl-4,6-diethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-formyl-piperazino)-6-methyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-allyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-trifluoromethyl-2-pyrimidinamine;
N-(2-bromo-4-methoxyethyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(2-thiopheno)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-cyanomethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-cyclopropylmethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-propargyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-methoxyethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-dimethylamino-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-dimethylamino-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-dimethylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methylthiomethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,6-dibromo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-diiodophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(N-methyl-2-hydroxyethylamino)-2-pyrimidinamine;
N-(2,6-dimethoxy-4-methylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-2,4-dimethoxy-6-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-6-methyl-4-(1-piperidinylcarbonyl)-2-pyrimidinamine;
methyl 2-((2-bromo-4-(1-methylethyl)phenyl)ethylamino)-6-methyl-4-pyrimidinecarboxylate;
2-((2-bromo-4-(1-methylethyl)phenyl)ethylamino)-N-cyclohexyl-6-methyl-4-pyrimidinecarboxamide;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-6-methyl-4-(4-methyl-1-piperazinylcarbonyl)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(thiomethyl)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(methylsulfinyl)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(methylsulfonyl)-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4(S)-(N-methyl-2′
-pyrrolidinomethoxy)-6-methyl-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylsulfinyl-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-(1-methylethyl)phenyl)-N-ethyl-4-thiazolidino-6-methyl-2-pyrimidinamine;
N-(2-iodo-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylsulfonyl-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-ethylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-ethylthio-4-methoxyiminoethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methoxyiminoethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylsulfonyl-4-methoxyiminoethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-bromo-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-ethyl-2-methylthiophenyl)-N-(1-methylethyl)-4,6-dimethyl-2-pyrimidinamine;
N-(4-ethyl-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(N-acetyl-N-methylamino)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-carboethoxy-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-methoxy-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-cyano-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-acetyl-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-propionyl-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-(1-methoxyethyl)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-(N-methylamino)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-(N,N-dimethylamino)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-formyl-6-methyl-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-hydroxyethoxymethyl-6-methyl-2-pyrimidinamine;
N-(2-Bromo-6-hydroxy-4-methoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(3-Bromo-4,6-dimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,3-Dibromo-4,6-dimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,6-Dibromo-4-(ethoxy)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(N-(2-furylmethyl)-N-methylamino)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-((4,4-ethylenedioxypiperidino)carbonyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-oxopiperidino)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-oxopiperidino)methyl-6-methylpyrimidinamine, hydrochloride salt;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(imidazol-1-yl)methyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(3-(methoxyphenyl)methoxymethyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-thiazolyl)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-imidazolyl)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(5-indolylcarbonyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-fluorophenyl)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(hydroxy-3-pyridyl-methyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-(methoxyphenyl)-3-pyridyl-hydroxymethyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(3-pyrazolyl)-6-methylpyrimidinamine, hydrochloride salt;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(1-aminoethyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-(4-tetrazolyl)-1-methylethyl)-6-methylpyrimidinamine;
2-(N-(2-bromo-4-(2-propyl)phenyl)amino)-4-carbomethoxy-6-methylpyrimidine; and
2-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-carbomethoxy-6-methylpyrimidine.
-
-
4. A compound of claim 1 selected from the group consisting of:
-
N-(2,4-dimethoxyphenyl)-N-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromophenyl)-N-allyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-dimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-dibromophenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-ethylphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-tert-butylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-tert-butylphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-trifluoromethylphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-trifluoromethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4,6-trimethoxyphenyl)-N-methyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4,6-trimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-allyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-n-butylphenyl)-N-propyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-cyclohexylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-allyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-methoxyethyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-cyanomethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-cyclopropylmethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-propargyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-methoxyethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-dimethylamino-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-dimethylamino-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-dimethylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methylthiomethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,6-dibromo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,4-diiodophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,6-dimethoxy-4-methylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylsulfinyl-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-iodo-4-methoxymethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylsulfonyl-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-ethylthio-4-(1-methylethyl)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-ethylthio-4-methoxyiminoethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-methoxyiminoethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylsulfonyl-4-methoxyiminoethylphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-bromo-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-ethyl-2-methylthiophenyl)-N-(1-methylethyl)-4,6-dimethyl-2-pyrimidinamine;
N-(4-ethyl-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-methylthio-4-(N-acetyl-N-methylamino)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-carboethoxy-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-methoxy-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-cyano-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-acetyl-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-propionyl-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-(1-methoxyethyl)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-(N-methylamino)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(4-(N,N-dimethylamino)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2-Bromo-6-hydroxy-4-methoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(3-Bromo-4,6-dimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine;
N-(2,3-Dibromo-4,6-dimethoxyphenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine; and
N-(2,6-Dibromo-4-(ethoxy)phenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine.
-
-
5. A compound of claim 1 selected from the group consisting of:
-
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4,6-diethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-formyl-piperazino)-6-methyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-trifluoromethyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(2-thiopheno)-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(N-methyl-2-hydroxyethylamino)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-2,4-dimethoxy-6-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-6-methyl-4-(1-piperidinylcarbonyl)-2-pyrimidinamine;
methyl 2-((2-bromo-4-(1-methylethyl)phenyl)ethylamino)-6-methyl-4-pyrimidinecarboxylate;
2-((2-bromo-4-(1-methylethyl)phenyl)ethylamino)-N-cyclohexyl-6-methyl-4-pyrimidinecarboxamide;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-6-methyl-4-(4-methyl-1-piperazinylcarbonyl)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(thiomethyl)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(methylsulfinyl)-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(methylsulfonyl)-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-formyl-6-methyl-2-pyrimidinamine;
N-(2-Bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-hydroxyethoxymethyl-6-methyl-2-pyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(N-(2-furylmethyl)-N-methylamino)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-((4,4-ethylenedioxypiperidino)carbonyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-oxopiperidino)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-oxopiperidino)methyl-6-methylpyrimidinamine, hydrochloride salt;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(imidazol-1-yl)methyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(3-(methoxyphenyl)methoxymethyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-thiazolyl)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-imidazolyl)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(5-indolylcarbonyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-fluorophenyl)carbonyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(hydroxy-3-pyridyl-methyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(4-(methoxyphenyl)-3-pyridyl-hydroxymethyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(3-pyrazolyl)-6-methylpyrimidinamine, hydrochloride salt;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(1-aminoethyl)-6-methylpyrimidinamine;
N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-(4-tetrazolyl)-1-methylethyl)-6-methylpyrimidinamine;
2-(N-(2-bromo-4-(2-propyl)phenyl)amino)-4-carbomethoxy-6-methylpyrimidine; and
2-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-carbomethoxy-6-methylpyrimidine.
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6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1.
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7. A method of treating affective disorders, anxiety, or depression in mammals in need of such treatment comprising administering to the mammals a therapeutically effective amount of a compound of claim 1.
Specification