Claims
- 1. A compound of formula: wherein Q is Z is C or N, provided that when Z is N, R2 is absent; X is CRaRb or NRa; Y is CH or N; provided that when Y is N, Z is C and X is CRaRb; and provided that when Y is CH, X is NRa; R1 is phenyl, mono- or poly-substituted phenyl, pyridyl, mono- or poly-substituted pyridyl, thienyl, or mono- or poly-substituted thienyl; wherein each of the substituents on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each of the substituents on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each of the substituents on the substituted thienyl is independently selected from halo, C1-C6 alkyl, and fluorinated C1-C6 alkyl; R2 is hydrogen, cyano, hydroxy, CO2Rc, C(═O)N(Rc)2, NRcC(═O)Rc, NRcSO2Rc, phenyl, mono- or poly-substituted phenyl, pyridyl, mono- or poly-substituted pyridyl, thienyl, or mono- or poly-substituted thienyl; wherein each of the substituents on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each of the substituents on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each of the substituents on the substituted thienyl is independently selected from halo, C1-C6 alkyl, and fluorinated C1-C6 alkyl; each R3 is a substituent at a ring atom other than Z or Y and is independently C1-C4 alkyl; R4, R5, R10 and R11 are each independently selected from hydrogen, C1-C6 alkyl, and C3-C8 cycloalkyl; R6 and R7 are taken together to form oxo; R8 and R9 are each independently selected from hydrogen, halo, cyano, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)Rc, C(═O)N(Rc)2, phenyl, mono- or poly-substituted phenyl, pyridyl, mono- or poly-substituted pyridyl, thienyl, and mono- or poly-substituted thienyl; wherein each of the substituents on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each of the substituents on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each of the substituents on the substituted thienyl is independently selected from halo, C1-C6 alkyl, and fluorinated C1-C6 alkyl; R12 is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, phenyl, mono- or poly-substituted phenyl, pyridyl, mono- or poly-substituted pyridyl, thienyl, mono- or poly-substituted thienyl, wherein each of the substituents on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each of the substituents on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each of the substituents on the substituted thienyl is independently selected from halo, C1-C6 alkyl, fluorinated C1-C6 alkyl;Raand Rb are each independently selected from hydrogen, C1-C6 alkyl, and C3-C8 cycloalkyl; Rc is hydrogen or C1-C6 alkyl; m is an integer of from 0 to 4; n is an integer of from 2 to 4, when X is NRa; n is an integer of from 1 to 3, when X is CRaRb; o and p are each integers of from 0 to 2, wherein the sum of o+p is less than or equal to 3; and q is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 2. The compound according to claim 1, wherein R1 is phenyl; mono-, di- or tri-substituted phenyl; pyridyl; mono- or di-substituted pyridyl; thienyl; or mono-substituted thienyl;R2 is hydrogen, cyano, hydroxy, CO2Rc, C(═O)N(Rc)2, NRcC(═O)Rc, NRcSO2Rc, phenyl, mono- or di- or tri-substituted phenyl, pyridyl, mono- or di-substituted pyridyl, thienyl, or mono-substituted thienyl; R4 and R5 are either both hydrogen, or one of R4 and R5 is hydrogen and the other is hydrogen, C1-C6 alkyl, or C3-C8 cycloalkyl; R8 and R9 are each independently selected from hydrogen, halo, cyano, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, C(═O)Rc, C(═O)N(Rc)2, phenyl, mono- or di-substituted phenyl, pyridyl, mono- or di-substituted pyridyl, thienyl and mono-substituted thienyl; and R10 and R11 are either both hydrogen, or one of R10 and R11 is hydrogen and the other is C1-C6 alkyl or C3-C8 cycloalkyl; and R12 is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C3-C8 cycloalkyl, fluorinated C1-C6 alkoxy, CO2Rc, phenyl, mono- or di-substituted phenyl, pyridyl, mono- or di-substituted pyridyl, thienyl, or mono-substituted thienyl, or a pharmaceutically acceptable salt thereof.
- 3. The compound according to claim 2, wherein in R1 each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each substituent on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each substituent on the substituted thienyl is independently selected from halo and C1-C4 alkyl;in R2 each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each substituent on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each substituent on the substituted thienyl is independently selected from halo and C1-C4 alkyl; in R8 and R9 each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each substituent on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each substituent on the substituted thienyl is independently selected from halo and C1-C4 alkyl; and in R12 each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each substituent on the substituted pyridyl is independently selected from halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; and each substituent on the substituted thienyl is independently selected from halo and C1-C4 alkyl; or a pharmaceutically acceptable salt thereof.
- 4. The compound according to claim 3, wherein each of R4, R5, R10 and R11 is hydrogen; and m is 0;or a pharmaceutically acceptable salt thereof.
- 5. The compound according to claim 1, wherein the compound is of formula: wherein A is C—R14 or N;R2 is hydrogen, cyano, hydroxy, CO2Rc, C(═O)N(Rc)2, NRcC(═O)Rc or NRcSO2Rc; R8 and R9 are each independently selected from hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)Rc, C(═O)N(Rc)2, phenyl, and mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 and SO2NH2; R12 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, phenyl, or mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each R14 is independently hydrogen, halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 or SO2N(Rc)2; Ra is hydrogen or C1-C6 alkyl; Rc is hydrogen or C1-C4 alkyl; and r is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 6. The compound according to claim 5, wherein the compound is selected from the group consisting ofcis-4-[3-(5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-phenylcyclohexanecarbonitrile; trans-4-[3-(5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-phenylcyclohexanecarbonitrile; cis-(3-{3-[4-cyano-4-(2-cyanophenyl)cyclohexylamino]propyl}-5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl) acetic acid methyl ester; cis-2-{1-cyano-4-[3-(3,5-dimethyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]cyclohexyl}benzonitrile; cis-2-{1-cyano-4-[3-(3-cyclopropylmethyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]cyclohexyl}benzonitrile; and pharmaceutically acceptable salts thereof.
- 7. The compound according to claim 5, wherein R12 is of formula: wherein each R16 is independently hydrogen, fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 or SO2NH2;q is 1; and s is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 8. The compound according to claim 1, wherein the compound is selected from the group consisting oftrans-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(2,4-difluorophenyl)cyclohexanecarbonitrile; trans-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-phenylcyclohexanecarbonitrile; 1-benzyl-3-{3-[1-(4-fluoro-2-methoxyphenyl)piperidin-4-ylamino]propyl}-5-methyl-1H-pyrimidine-2,4-dione; trans-1-benzyl-3-{3-[4-(2-methoxyphenyl)cyclohexylamino]propyl}-5-methyl-1H-pyrimidine-2,4-dione; 2-{4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]cyclohexyl}benzonitrile; trans-2-{4-[3-(3-benzyl-2,6-dioxo-5-phenyl-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-cyanocyclohexyl}benzonitrile; and pharmaceutically acceptable salts thereof.
- 9. The compound according to claim 7, wherein the compound is of formula wherein R8 is hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)Rc, or C(═O)N(Rc)2; ora pharmaceutically acceptable salt thereof.
- 10. The compound according to claim 9, wherein the compound is selected from the group consisting ofcis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(2,4-difluorophenyl)cyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-phenylcyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(3,5-difluorophenyl)cyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(2-methoxyphenyl)cyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(2-trifluoromethylphenyl)cyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(4-fluoro-2-trifluoromethylphenyl)cyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(2,4-dichlorophenyl)cyclohexanecarbonitrile; cis-2-{4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-cyanocyclohexyl}benzonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-(2-trifluoromethoxyphenyl)cyclohexanecarbonitrile; cis-4-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-pyridin-2-ylcyclohexanecarbonitrile; cis-2-{4-[3-(3-benzyl-2,6-dioxo-5-phenyl-3,6-dihydro-2H-pyrimidin-1-yl)propylamino]-1-cyanocyclohexyl}benzonitrile; and pharmaceutically acceptable salts thereof.
- 11. The compound according to claim 1, wherein the compound is of formula: wherein A is C—R14 or N;R2 is hydrogen, cyano, hydroxy, CO2Rc, C(═O)N(Rc)2, NRcC(═O)Rc or NRcSO2Rc; R8 and R9 are each independently selected from hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)Rc, C(═O)N(Rc)2, phenyl, and mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 and SO2NH2; R12 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, phenyl, or mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each R14 is independently hydrogen, halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 or SO2N(Rc)2; Rc is hydrogen or C1-C4 alkyl; and r is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 12. The compound according to claim 11, wherein R12 is of formula: wherein each R16 is independently hydrogen, fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 or SO2NH2;q is 1; and s is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 13. The compound according to claim 12, wherein the compound is selected from the group consisting of1-benzyl-3-{3-[4-(4-fluorophenyl)piperidin-1-yl]propyl}-5-methyl-1H-pyrimidine-2,4-dione; 1-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propyl]-4-ortho-tolylpiperidine-4-carbonitrile; 2-{1-[3-(3-benzyl-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl)propyl]piperidin-4-yl}benzonitrile; and pharmaceutically acceptable salts thereof.
- 14. The compound according to claim 1, wherein the compound is of formula wherein A is C—R14 or N;R8 and R9 are each independently selected from hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)Rc, C(═O)N(Rc)2, phenyl, and mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 and SO2NH2; R12 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, phenyl, or mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each R14 is independently hydrogen, halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 or SO2N(Rc)2; Ra is hydrogen or C1-C6 alkyl; Rc is hydrogen or C1-C4 alkyl; and r is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 15. The compound according to claim 14, wherein the compound is 3-{3-[1-(4-fluoro-2-methoxyphenyl)piperidin-4-ylamino]propyl}-5-methyl-1H-pyrimidine-2,4-dione; or a pharmaceutically acceptable salt thereof.
- 16. The compound according to claim 14, wherein R12 is of formula: wherein each R16 is independently hydrogen, fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethlyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 or SO2NH2;q is 1; and s is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 17. The compound according to claim 1, wherein the compound is of formula: wherein A is C—R14 or N;R2 is hydrogen, cyano, hydroxy, CO2Rc, C(═O)N(Rc)2, NRcC(═O)Rc or NRcSO2Rc; R8 and R9 are each independently selected from hydrogen, halo, cyano, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)Rc, C(═O)N(Rc)2, phenyl, and mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 and SO2NH2; R12 is hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, phenyl, or mono- or di-substituted phenyl; wherein each substituent on the substituted phenyl is independently selected from halo, nitro, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 and SO2N(Rc)2; each R14 is independently hydrogen, halo, cyano, hydroxy, amino, C1-C4 alkyl, C1-C4 alkoxy, fluorinated C1-C4 alkyl, fluorinated C1-C4 alkoxy, CO2Rc, C(═O)N(Rc)2 or SO2N(Rc)2; Ra is hydrogen or C1-C6 alkyl; Rc is hydrogen or C1-C4 alkyl; and r is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 18. The compound according to claim 17, wherein R12 is of formula: wherein each R16 is independently hydrogen, fluoro, chloro, nitro, cyano, hydroxy, amino, methyl, ethyl, methoxy, ethoxy, trifluromethyl, trifluoromethoxy, trifluoroethoxy, CO2CH3, C(═O)NH2 or SO2NH2;q is 1; and s is an integer of from 0 to 2; or a pharmaceutically acceptable salt thereof.
- 19. The compound according to claim 18, wherein the compound is selected from the group consisting ofcis-2-{4-[3-(3-benzyl-5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)propylamino]-1-cyanocyclohexyl}benzonitrile; trans-2-{4-[3-(3-benzyl-5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)propylamino]-1-cyanocyclohexyl}benzonitrile; and pharmaceutically acceptable salts thereof.
- 20. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.
- 21. A pharmaceutical composition made by combining the compound according to claim 1 and a pharmaceutically acceptable carrier.
- 22. A process for making a pharmaceutical composition comprising combining the compound according to claim 1 and a pharmaceutically acceptable carrier.
- 23. The composition according to claim 20 further comprising a testosterone 5-alpha reductase inhibitor.
- 24. The composition according to claim 23, wherein the testosterone 5-alpha reductase inhibitor is a type 1, a type 2, both a type 1 and a type 2, or a dual type 1 and type 2 testosterone 5-alpha reductase inhibitor.
- 25. The composition according to claim 24, wherein the testosterone 5-alpha reductase inhibitor is a type 2 testosterone 5-alpha reductase inhibitor.
- 26. The composition according to claim 25, wherein the testosterone 5-alpha reductase inhibitor is finasteride.
- 27. A method of treating benign prostatic hyperplasia in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1.
- 28. The method according to claim 27, wherein the compound does not cause a fall in blood pressure at dosages effective to alleviate benign prostatic hyperlasia.
- 29. The method according to claim 27, wherein the compound is administered in combination with a testosterone 5-alpha reductase inhibitor.
- 30. The method according to claim 29, wherein the testosterone 5-alpha reductase inhibitor is finasteride.
- 31. A method of treating benign prostatic hyperplasia in a subject in need thereof which comprises administering a therapeutically effective amount of the composition according to claim 20.
- 32. The method according to claim 31, wherein the composition further comprises a therapeutically effective amount of a testosterone 5-alpha reductase inhibitor.
- 33. A method of relaxing lower urinary tract tissue in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1.
- 34. The method according to claim 33, wherein the compound is administered in combination with a testosterone 5-alpha reductase inhibitor.
- 35. The method according to claim 34, wherein the testosterone 5-alpha reductase inhibitor is finasteride.
- 36. A method of treating a condition which is susceptible to treatment by antagonism of the alpha 1a receptor which comprises administering to a subject in need thereof an amount of the compound according to claim 1 effective to treat the condition.
- 37. A method of eliciting an alpha 1a antagonizing effect in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the compound according to claim 1.
Parent Case Info
This application claims the benefit of U.S. Provisional Application No. 60/108,146, filed Nov. 12, 1998.
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Number |
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Nov 1998 |
US |