Claims
- 1. A compound of Formula (IA)
- 2. The compound of claim 1 wherein
X and Y are CR and Z is N, or X is N and Y and Z are CR, where R for each occurrence is hydrogen, halogen, or (C1-C4)alkyl;
(i) R1a is halogen, (C1-C4)alkyl, trifluoromethyl, methoxy, or trifluoromethoxy, and R1b, R1d and R1e are each hydrogen, (ii) R1b is halogen, methyl, or methoxy and R1a, R1d and R1e are each hydrogen, (iii) R1a and R1b are each independently halogen or methyl and R1d and R1e are each hydrogen, (iv) R1b and R1d are each independently halogen or methyl and R1a and R1e are each hydrogen, (v) R1a and R1d are each independently halogen or methyl and R1b, and R1e are each hydrogen, (vi) R1a and R1e are each independently halogen or methyl and R1b and R1d are each hydrogen, or (vii) R1a, R1b and R1d are each independently halogen or methyl and R1e is hydrogen; W is oxy or amino; n is 1 or 2; R2a and R2b are each independently methyl or hydrogen; R3a and R3b are each independently hydrogen or (C1-C2)alkyl; and R4 is hydrogen or (C1-C4)alkyl; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 3. The compound of claim 1 wherein
Z is N; X is CH; Y is CR, where R is hydrogen or methyl;
(i) R1a is halogen, (C1-C4)alkyl, trifluoromethyl, methoxy, or trifluoromethoxy, and R1b, R1d and R1e are each hydrogen, (ii) R1b is halogen, methyl or methoxy and R1a, R1d and R1e are each hydrogen, (iii) R1a and R1b are each independently halogen or methyl and R1d and R1e are each hydrogen, (iv) R1b and R1d are each independently halogen or methyl and R1a and R1e are each hydrogen, (v) R1a and R1d are each independently halogen or methyl and R1b and R1e are each hydrogen, (vi) R1a and R1e are each independently halogen or methyl and R1b and R1d are each hydrogen, or (vii) R1a, R1b and R1d are each independently halogen or methyl and R1e is hydrogen; W is oxy or amino; n is 1; R2a and R2b are each independently methyl or hydrogen; and R3a is hydrogen, (2R)-methyl, or (2R)-ethyl; and R3b is hydrogen; and R4 is hydrogen or (C1-C4)alkyl; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 4. The compound of claim 1 wherein
X is N; Y is CR, where R is hydrogen or methyl; Z is CH;
(i) R1a is halogen, (C1-C4)alkyl, trifluoromethyl, methoxy or trifluoromethoxy and R1b, R1d and R1e are each hydrogen; (ii) R1b is halogen or methoxy and R1a, R1d and R1e are each hydrogen, (iii) R1b and R1d are each independently halogen or methyl and R1a and R1e are each hydrogen, or (iv) R1a and R1d are each independently halogen or methyl and R1b and R1e are each hydrogen; W is amino; n is 1; R2a and R2b are each independently methyl or hydrogen; R3a is hydrogen, (2R)-methyl, or (2R)-ethyl; and R3b is hydrogen; and R4 is hydrogen or (C1-C4)alkyl; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 5. The compound of claim 1 selected from the group consisting of
2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3-methoxy-benzyloxy)-4-piperazin-1-yl-pyrimidine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(2-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 6. The compound of claim 1 selected from the group consisting of
2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 7. The compound of claim 1 selected from the group consisting of
2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, hydrochloride; (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, hydrochloride; (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, fumarate; 2-(2,3-difluoro-benzyl oxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; and 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride.
- 8. A pharmaceutical composition comprising
(1) a compound of Formula (IA) 10wherein X and Y are CR and Z is N, or X is N and Y and Z are CR, where R for each occurrence is hydrogen, halogen, (C1-C4)alkyl, amino, or (C1-C4)alkylamino; W is oxy, thio, amino, (C1-C4)alkylamino, or acetylamino; at least one of R1a, R1b, R1d, and R1e is independently selected from the group consisting of halogen, nitro, amino, cyano, —C(O)NH2, (C1-C4)alkyl, halo-substituted(C1-C4)alkyl, (C1-C4) alkoxy, and halo-substituted(C1-C4)alkoxy, or R1a and R1b taken together form a five- or six-membered, aromatic or partially or fully saturated fused ring, or R1a taken together with R2a or R2b forms a five- or six-membered, fully saturated fused ring; R1c is hydrogen; R2a and R2b are each independently hydrogen, (C1-C4)alkyl, partially or fully saturated (C3-C6)cycloalkyl, or one of which taken together with R1a forms a five- or six-membered, fully saturated fused ring; n is 0, 1, or 2; R3a and R3b are each independently hydrogen, (C1-C4)alkyl, or (C1-C4)alkyl substituted with hydroxy, fluoro, or (C1-C4)alkoxy; R4 is hydrogen, hydroxy, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy or cyano, (C1-C4)alkylcarbonyl, (C1-C4)alkoxy, (C1-C4)alkoxy-carbonyl, (C3-C4)alkenyl, or an amino-protecting group; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt; and (2) a pharmaceutically acceptable excipient, diluent, or carrier
- 9. The composition of claim 8 wherein said compound of Formula (IA) is a compound where
X and Y are CR and Z is N, or X is N and Y and Z are CR, where R for each occurrence is hydrogen, halogen, or (C1-C4)alkyl;
(i) R1a is halogen, (C1-C4)alkyl, trifluoromethyl, methoxy, or trifluoromethoxy, and R1b, R1d and R1e are each hydrogen, (ii) R1b is halogen, methyl, or methoxy and R1a, R1d and R1e are each hydrogen, (iii) R1a and R1b are each independently halogen or methyl and R1d and R1e are each hydrogen, (iv) R1b and R1d are each independently halogen or methyl and R1a and R1e are each hydrogen, (v) R1a and R1d are each independently halogen or methyl and R1b, and R1e are each hydrogen, (vi) R1a and R1e are each independently halogen or methyl and R1b and R1d are each hydrogen, or (vii) R1a, R1b and R1d are each independently halogen or methyl and R1e is hydrogen; W is oxy or amino; n is 1 or 2; R2a and R2b are each independently methyl or hydrogen; R3a and R3b are each independently hydrogen or (C1-C2)alkyl; and R4 is hydrogen or (C1-C4)alkyl; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 10. The composition of claim 8 wherein said compound of Formula (IA) is a compound where
Z is N; X is CH; Y is CR, where R is hydrogen or methyl;
(i) R1a is halogen, (C1-C4)alkyl, trifluoromethyl, methoxy, or trifluoromethoxy, and R1b, R1d and R1e are each hydrogen, (ii) R1b is halogen or methoxy and R1a, R1d and R1e are each hydrogen, (iii) R1a and R1b are each independently halogen or methyl and R1d and R1e are each hydrogen, (iv) R1b and R1d are each independently halogen or methyl and R1b and R1e are each hydrogen, (v) R1a and R1d are each independently halogen or methyl and R1b and R1e are each hydrogen, (vi) R1a and R1e are each independently halogen or methyl and R1b and R1d are each hydrogen, or (vii) R1a, R1b and R1d are each independently halogen or methyl and R1e is hydrogen; W is oxy or amino; n is 1; R2a and R2b are each independently methyl or hydrogen; and R3a is hydrogen, (2R)-methyl, or (2R)-ethyl; and R3b is hydrogen; and R4 is hydrogen or (C1-C4)alkyl; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 11. The composition of claim 8 wherein said compound of Formula (IA) is a compound where
X is N; Y is CR, where R is hydrogen or methyl; Z is CH;
(i) R1a is halogen, (C1-C4)alkyl, trifluoromethyl, methoxy or trifluoromethoxy and R1b, R1d and R1e are each hydrogen; (ii) R1b is halogen, methyl, or methoxy and R1a, R1d and R1e are each hydrogen, (iii) R1b and R1d are each independently halogen or methyl and R1a and R1e are each hydrogen, or (iv) R1a and R1d are each independently halogen or methyl and R1b and R1e are each hydrogen; W is amino; n is 1; R2a and R2b are each independently methyl or hydrogen; R3a is hydrogen, (2R)-methyl, or (2R)-ethyl; and R3b is hydrogen; and R4 is hydrogen or (C1-C4)alkyl; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 12. The pharmaceutical composition of claim 8 wherein said compound of Formula (IA) is selected from the group consisting of
2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3-methoxy-benzyloxy)-4-piperazin-1-yl-pyrimidine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(2-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine, a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 13. The pharmaceutical composition of claim 8 wherein said compound of Formula (IA) is selected from the group consisting of
2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 14. The pharmaceutical composition of claim 8 wherein said pharmaceutically acceptable salt is selected from the group consisting of
2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, hydrochloride; (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, hydrochloride; (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, fumarate; 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; and 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride.
- 15. The pharmaceutical composition of claim 8, 9, 10, 11, 12, 13, or 14 further comprising at least one other pharmaceutical agent.
- 16. The pharmaceutical composition of claim 15 wherein said at least one other pharmaceutical agent is an anti-obesity agent.
- 17. The pharmaceutical composition of claim 16 wherein said anti-obesity agent is selected from the group consisting of an apo-B/MTP inhibitor, an MCR-4 agonist, a CCK-A agonist, a monoamine reuptake inhibitor, a sympathomimetic agent, a P3 adrenergic receptor agonist, a dopamine agonist, a melanocyte-stimulating hormone receptor analog, a cannabinoid 1 receptor antagonist, a melanin concentrating hormone antagonist, leptin, a leptin analog, a leptin receptor agonist, a galanin antagonist, a lipase inhibitor, a bombesin agonist, a neuropeptide-Y antagonist, a thyromimetic agent, dehydroepiandrosterone or an analog thereof, a glucocorticoid receptor agonist or antagonist, an orexin receptor antagonist, a urocortin binding protein antagonist, a glucagon-like peptide-1 receptor agonist, a ciliary neurotrophic factor, a human agouti-related protein, a ghrelin receptor antagonist, a histamine 3 receptor antagonist or reverse agonist, and a neuromedin U receptor agonist.
- 18. The pharmaceutical composition of claim 16 wherein said anti-obesity agent is selected from the group consisting of orlistat, sibutramine, bromocriptine, ephedrine, leptin, and pseudoephedrine.
- 19. A pharmaceutical composition comprising (1) a compound of Formula (IB)
- 20. The pharmaceutical composition of claim 19 wherein said anti-obesity agent is selected from the group consisting of an apo-B/MTP inhibitor, an MCR-4 agonist, a CCK-A agonist, a monoamine reuptake inhibitor, a sympathomimetic agent, a β3 adrenergic receptor agonist, a dopamine agonist, a melanocyte-stimulating hormone receptor analog, a cannabinoid 1 receptor antagonist, a melanin concentrating hormone antagonist, leptin, a leptin analog, a leptin receptor agonist, a galanin antagonist, a lipase inhibitor, a bombesin agonist, a neuropeptide-Y antagonist, a thyromimetic agent, dehydroepiandrosterone or an analog thereof, a glucocorticoid receptor agonist or antagonist, an orexin receptor antagonist, a urocortin binding protein antagonist, a glucagon-like peptide-1 receptor agonist, a ciliary neurotrophic factor, a human agouti-related protein, a ghrelin receptor antagonist, a histamine 3 receptor antagonist or reverse agonist, and a neuromedin U receptor agonist.
- 21. The pharmaceutical composition of claim 19 wherein said anti-obesity agent is selected from the group consisting of orlistat, sibutramine, bromocriptine, ephedrine, leptin, and pseudoephedrine.
- 22. The pharmaceutical composition of claim 19, 20 or 21 wherein said compound of Formula (IB) is selected from the group consisting of
2-benzyloxy-4-methyl-6-piperazin-1-yl-pyrimidine, 2-benzyloxy-4-piperazin-1-yl-pyrimidine, 4-benzyloxy-2-piperazin-1-yl-pyrimidine, benzyl-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, benzyl-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3-methoxy-benzyloxy)-4-piperazin-1-yl-pyrimidine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(2-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine, a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 23. The pharmaceutical composition of claim 22 wherein said pharmaceutically acceptable salt is selected from the group consisting of
2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, hydrochloride; (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, hydrochloride; (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, fumarate; 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3,5-dichloro-benzyloxy)4-piperazin-1-yl-pyrimidine, hydrochloride; and 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride.
- 24. The pharmaceutical composition of claim 19, 20 or 21 wherein said compound of Formula (IB) is selected from the group consisting of
2-benzyloxy-4-methyl-6-piperazin-1-yl-pyrimidine, benzyl-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, benzyl-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, 4-benzyloxy-2-piperazin-1-yl-pyrimidine, 2-benzyloxy-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 25. A method for treating a 5-HT2 receptor-mediated disease, condition, or disorder in an animal comprising the step of administering to said animal a therapeutically effective amount of a compound of Formula of (IB)
- 26. The method of claim 25 wherein said compound of Formula (IB) is selected from the group consisting of
2-benzyloxy-4-methyl-6-piperazin-1-yl-pyrimidine, 2-benzyloxy-4-piperazin-1-yl-pyrimidine, 4-benzyloxy-2-piperazin-1-yl-pyrimidine, benzyl-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, benzyl-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2-chloro-benzyloxy)4-piperazin-1-yl-pyrimidine, 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3-methoxy-benzyloxy)-4-piperazin-1-yl-pyrimidine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-2-yl)-amine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-1-(3-fluoro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(2-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-dichloro-benzyloxy)4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine, a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 27. The method of claim 26 wherein said pharmaceutically acceptable salt is selected from the group consisting of
2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, hydrochloride; (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, hydrochloride; (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, hydrochloride; (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, fumarate; 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride; and 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, hydrochloride.
- 28. The method of claim 25 wherein said compound of Formula (IB) is selected from the group consisting of
2-benzyloxy-4-methyl-6-piperazin-1-yl-pyrimidine, benzyl-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, benzyl-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, 4-benzyloxy-2-piperazin-1-yl-pyrimidine, 2-benzyloxy-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 29. The method of claim 25. 26, 27, or 28 wherein said 5-HT2 receptor-mediated disease, condition or disorder is a 5-HT2c receptor-mediated disease, condition or disorder.
- 30. The method of claim 25, 26, 27, or 28 wherein said 5-HT2 receptor-mediated disease, condition, or disorder is selected from the group consisting of weight loss, obesity, bulimia, premenstrual syndrome or late luteal phase syndrome, depression, a typical depression, bipolar disorders, psychoses, schizophrenia, migraine, alcoholism, tobacco abuse, panic disorder, anxiety, post-traumatic syndrome, memory loss, dementia of aging, social phobia, attention deficit hyperactivity disorder, disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, sexual dysfunction in males, sexual dysfunction in females, anorexia nervosa, disorders of sleep, autism, seizure disorders, epilepsy, mutism, spinal cord injury, damage of the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, and type II diabetes.
- 31. A method for treating or preventing a 5-HT2 receptor-mediated disease, condition, or disorder in an animal comprising the step of administering to said animal a therapeutically effective amount of a pharmaceutical composition of claim 8, 9, 10, 11, 12, 13, or 14.
- 32. The method of claim 31 wherein said 5-HT2 receptor-mediated disease, condition or disorder is a 5-HT2c receptor-mediated disease, condition or disorder.
- 33. The method of claim 31 wherein said 5-HT2 receptor-mediated disease, condition, or disorder is selected from the group consisting of weight loss, obesity, bulimia, premenstrual syndrome or late luteal phase syndrome, depression, a typical depression, bipolar disorders, psychoses, schizophrenia, migraine, alcoholism, tobacco abuse, panic disorder, anxiety, post-traumatic syndrome, memory loss, dementia of aging, social phobia, attention deficit hyperactivity disorder, disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, sexual dysfunction in males, sexual dysfunction in females, anorexia nervosa, disorders of sleep, autism, seizure disorders, epilepsy, mutism, spinal cord injury, damage of the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, and type II diabetes.
- 34. A method for treating or preventing a 5-HT2 receptor-mediated disease, condition, or disorder in an animal comprising the step of administering to said animal a therapeutically effective amount of a pharmaceutical composition of claim 19, 20 or 21.
- 35. The method of claim 34 wherein said pharmaceutical composition comprises a compound of Formula (IB) selected from the group consisting of
2-benzyloxy-4-methyl-6-piperazin-1-yl-pyrimidine, 2-benzyloxy-4-piperazin-1-yl-pyrimidine, 4-benzyloxy-2-piperazin-1-yl-pyrimidine, benzyl-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, benzyl-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-(2-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-fluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3-methoxy-benzyloxy)-4-piperazin-1-yl-pyrimidine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, 2-[1-(3-fluoro-phenyl)-ethoxy]4-methyl-6-piperazin-1-yl-pyrimidine, 2-[1-(3-fluoro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(2-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-piperazin-1-yl-pyrimidine, 2-[1-(3-chloro-phenyl)-ethoxy]-4-methyl-6-piperazin-1-yl-pyrimidine, 2-(213-difluoro-benzyloxy]4-piperazin-1-yl-pyrimidine, 2-(2 5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine, a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 36. The method of claim 34 wherein said pharmaceutical composition comprises a compound of Formula (IB) selected from the group consisting of
2-benzyloxy-4-methyl-6-piperazin-1-yl-pyrimidine, benzyl-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, benzyl-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, 4-benzyloxy-2-piperazin-1-yl-pyrimidine, 2-benzyloxy-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(3-chloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, (3-chloro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-chloro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-fluoro-benzyl)-(4-piperazin-1-yl-pyrimidin-2-yl)-amine, (3-fluoro-benzyl)-(2-piperazin-1-yl-pyrimidin-4-yl)-amine, (3-chloro-benzyl)-(3 ,4 ,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-6′-yl)-amine, 2-(2,3-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-piperazin-1-yl-pyrimidine, 2-(2,5-difluoro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(2,5-dichloro-benzyloxy)-4-(2(R)-methyl-piperazin-1-yl)-pyrimidine, 2-(3,5-dichloro-benzyloxy)-4-piperazin-1-yl-pyrimidine, and 4-piperazin-1-yl-2-(2,3,5-trifluoro-benzyloxy)-pyrimidine; a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 37. The method of claim 34 wherein said 5-HT2 receptor-mediated disease, condition or disorder is a 5-HT2c receptor-mediated disease, condition or disorder.
- 38. The method of claim 34 wherein said 5-HT2 receptor-mediated disease, condition, or disorder is selected from the group consisting of weight loss, obesity, bulimia, premenstrual syndrome or late luteal phase syndrome, depression, a typical depression, bipolar disorders, psychoses, schizophrenia, migraine, alcoholism, tobacco abuse, panic disorder, anxiety, post-traumatic syndrome, memory loss, dementia of aging, social phobia, attention deficit hyperactivity disorder, disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, sexual dysfunction in males, sexual dysfunction in females, anorexia nervosa, disorders of sleep, autism, seizure disorders, epilepsy, mutism, spinal cord injury, damage of the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, and type II diabetes.
- 39. A pharmaceutical kit comprising
(a) a dosage form comprising a compound of Formula (IB) 13X and Y are CR and Z is N, or X is N and Y and Z are CR, where R for each occurrence is hydrogen, halogen, (C1-C4)alkyl, amino, or (C1-C4)alkylamino; W is oxy, thio, amino, (C1-C4)alkylamino, or acetylamino; R1a, R1b, R1c, R1d and R1e are each independently hydrogen, halogen, nitro, cyano, amino, (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, (C1-C4)alkoxy, halo-substituted (C1-C4)alkoxy, —C(O)NH2, R1a and R1b taken together form a five- or six-membered, aromatic or partially or fully saturated fused ring, or R1a taken together with R2a or R2b forms a five- or six-membered, fully saturated, fused ring; R2a and R2b are each independently hydrogen, (C1-C4)alkyl, partially or fully saturated (C3-C6)cycloalkyl, or one of which taken together with R1a forms a five- or six-membered, fully saturated fused ring; n is 0, 1, or 2; R3a and R3b are each independently hydrogen, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy, fluoro, or (C1-C4)alkoxy; R4 is hydrogen, hydroxy, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy or cyano, (C1-C4)alkylcarbonyl, (C1-C4)alkoxy, (C1-C4)alkoxy-carbonyl, or (C3-C4)alkenyl; a nitrogen oxide thereof, a prodrug of the compound or the nitrogen oxide; a pharmaceutically acceptable salt of the compound, the nitrogen oxide, or the prodrug, or a solvate or hydrate of the compound, the nitrogen oxide, the prodrug, or the salt; and (b) instructions describing a method of using said dosage form to treat or prevent a 5-HT2 receptor-mediated disease, condition, or disorder.
- 40. A pharmaceutical kit comprising
(a) a first unit dosage form comprising
(i) a compound of Formula (IB) 14wherein
X and Y are CR and Z is N, or X is N and Y and Z are CR, where R for each occurrence is hydrogen, halogen, (C1-C4)alkyl, amino, or (C1-C4)alkylamino; W is oxy, thio, amino, (C1-C4)alkylamino, or acetylamino; R1a, R1b, R1c, R1d and R1e are each independently hydrogen, halogen, nitro, cyano, amino, (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, (C1-C4)alkoxy, halo-substituted (C1-C4)alkoxy, —C(O)NH2, R1a and R1b taken together form a five- or six-membered, aromatic or partially or fully saturated fused ring, or R1a taken together with R2a or R2b forms a five- or six-membered, fully saturated, fused ring; R2a and R2b are each independently hydrogen, (C1-C4)alkyl, partially or fully saturated (C3-C6)cycloalkyl, or one of which taken together with R1a forms a five- or six-membered, fully saturated fused ring; n is 0,1, or 2; R3a and R3b are each independently hydrogen, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy, fluoro, or (C1-C4)alkoxy; R4 is hydrogen, hydroxy, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy or cyano, (C1-C4)alkylcarbonyl, (C1-C4)alkoxy, (C1-C4)alkoxy-carbonyl, or (C3-C4)alkenyl; a nitrogen oxide thereof, a prodrug of the compound or the nitrogen oxide; a pharmaceutically acceptable salt of the compound, the nitrogen oxide, or the prodrug, or a solvate or hydrate of the compound, the nitrogen oxide, the prodrug, or the salt; and (ii) a pharmaceutically acceptable carrier, excipient, diluent, or a mixture thereof; b) a second dosage form comprising
(i) at least one additional pharmaceutical agent selected from the group consisting of an apo-B/MTP inhibitor, an MCR-4 agonist, a CCK-A agonist, a monoamine reuptake inhibitor, a sympathomimetic agent, a 3 adrenergic receptor agonist, a dopamine agonist, a melanocyte-stimulating hormone receptor analog, a cannabinoid 1 receptor antagonist, a melanin concentrating hormone antagonist, leptin, a leptin analog, a leptin receptor agonist, a galanin antagonist, a lipase inhibitor, a bombesin agonist, a neuropeptide-Y antagonist, a thyromimetic agent, dehydroepiandrosterone or an analog thereof, a glucocorticoid receptor agonist or antagonist, an orexin receptor antagonist, a urocortin binding protein antagonist, a glucagon-like peptide-1 receptor agonist, a ciliary neurotrophic factor, a human agouti-related protein, a ghrelin receptor antagonist, a histamine 3 receptor antagonist or reverse agonist, and a neuromedin U receptor agonist; and (ii) a pharmaceutically acceptable carrier, excipient, diluent, or a mixture thereof; and c) a container.
- 41. A method for treating or preventing a 5-HT2 receptor-mediated disease, condition, or disorder comprising administering to an animal in need of such treatment
a) a therapeutically effective amount of a compound of Formula (IB) 15X and Y are CR and Z is N, or X is N and Y and Z are CR, where R for each occurrence is hydrogen, halogen, (C1-C4)alkyl, amino, or (C1-C4)alkylamino; W is oxy, thio, amino, (C1-C4)alkylamino, or acetylamino; R1a, R1b, R1c, R1d and R1e are each independently hydrogen, halogen, nitro, cyano, amino, (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, (C1-C4)alkoxy, halo-substituted (C1-C4)alkoxy, —C(O)NH2, R1a and R1b taken together form a five- or six-membered, aromatic or partially or fully saturated fused ring, or R1a taken together with R2a or R2b forms a five- or six-membered, fully saturated, fused ring; R2a and R2b are each independently hydrogen, (C1-C4)alkyl, partially or fully saturated (C3-C6)cycloalkyl, or one of which taken together with R1a forms a five- or six-membered, fully saturated fused ring; n is 0, 1, or 2; R3a and R3b are each independently hydrogen, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy, fluoro, or (C1-C4)alkoxy; R4 is hydrogen, hydroxy, (C1-C4)alkyl, (C1-C4)alkyl substituted with hydroxy or cyano, (C1-C4)alkylcarbonyl, (C1-C4)alkoxy, (C1-C4)alkoxy-carbonyl, or (C3-C4)alkenyl; a nitrogen oxide thereof, a prodrug of the compound or the nitrogen oxide; a pharmaceutically acceptable salt of the compound, the nitrogen oxide, or the prodrug, or a solvate or hydrate of the compound, the nitrogen oxide, the prodrug, or the salt; and b) a therapeutically effective amount of at least one additional pharmaceutical agent selected from the group consisting of an apo-B/MTP inhibitor, an MCR-4 agonist, a CCK-A agonist, a monoamine reuptake inhibitor, a sympathomimetic agent, a 3 adrenergic receptor agonist, a dopamine agonist, a melanocyte-stimulating hormone receptor analog, a cannabinoid 1 receptor antagonist, a melanin concentrating hormone antagonist, leptin, a leptin analog, a leptin receptor agonist, a galanin antagonist, a lipase inhibitor, a bombesin agonist, a Neuropeptide-Y antagonist, a thyromimetic agent, dehydroepiandrosterone or an analog thereof, a glucocorticoid receptor agonist or antagonist, an orexin receptor antagonist, a urocortin binding protein antagonist, a glucagon-like peptide-1 receptor agonist, a ciliary neurotrophic factor, an AGRP, a ghrelin receptor antagonist, a histamine 3 receptor antagonist or reverse agonist, and a neuromedin U receptor agonist.
- 42. The method of claim 41 wherein said compound of Formula (IB), a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt, and said at least one additional pharmaceutical agent is administered simultaneously.
- 43. The method of claim 41 wherein said compound of Formula (IB), a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt, and said at least one additional pharmaceutical agent is administered sequentially.
- 44. The method of claim 41 wherein said compound of Formula (IB), a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt, and said at least one additional pharmaceutical agent is administered as a single pharmaceutical composition comprising said compound of Formula (IB), a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt, said at least one additional pharmaceutical agent, and a pharmaceutically acceptable excipient, diluent, carrier or a mixture thereof.
- 45. The method of claim 41 wherein said compound of Formula (IB), a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt, and said at least one pharmaceutical agent is administered as two separate pharmaceutical compositions comprising (i) a first composition comprising said compound of Formula (IB), a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt, and a pharmaceutically acceptable excipient, diluent, or carrier; and (ii) a second composition comprising said at least one pharmaceutical agent and a pharmaceutically acceptable excipient, diluent, or carrier.
- 46. The method of claim 45 wherein said first composition and said second composition is administered simultaneously.
- 47. The method of claim 45 wherein said first composition and said second composition is administered sequentially.
- 48. The method of claim 41, 42, 43, 44, 45, 46, or 47 wherein said 5-HT2 receptor-mediated disease, condition or disorder is a 5-HT2c receptor-mediated, condition or disorder.
- 49. A method of increasing lean meat content in an edible animal comprising the step of administering to said edible animal a lean meat increasing amount of a compound of Formula (IB)
- 50. A method of increasing lean meat content in an edible animal comprising the step of administering to said edible animal a lean meat increasing amount of a pharmaceutical composition of claim 8, 9, 10, 11, 12, 13, 14,15,19, 20, or 21.
- 51. A compound of Formula (IC)
- 52. The compound of claim 51 selected from the group consisting of 4-piperazin-1-yl-2-(pyridin-2-ylmethoxy)-pyrimidine, 2-(6-methyl-pyridin-2-ylmethoxy)-4-piperazin-1-yl-pyrimidine, and 2-(6-chloro-pyridin-2-ylmethoxy)-4-piperazin-1-yl-pyrimidine;
a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 53. The compound of claim 51 selected from the group consisting of 2-(6-methyl-pyridin-2-ylmethoxy)-4-piperazin-1-yl-pyrimidine and 2-(6-chloro-pyridin-2-ylmethoxy)-4-piperazin-1-yl-pyrimidine;
a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 54. A method for treating or preventing a 5-HT2 receptor-mediated disease, condition, or disorder in an animal comprising the step of administering to said animal a therapeutically effective amount of a compound of claim 51, a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.
- 55. The method of claim 54 wherein said 5-HT2 receptor-mediated disease, condition or disorder is a 5-HT2c receptor-mediated disease, condition or disorder.
- 56. The method of claim 54 wherein said 5-HT2 receptor-mediated disease, condition, or disorder is selected from the group consisting of weight loss, obesity, bulimia, premenstrual syndrome or late luteal phase syndrome, depression, a typical depression, bipolar disorders, psychoses, schizophrenia, migraine, alcoholism, tobacco abuse, panic disorder, anxiety, post-traumatic syndrome, memory loss, dementia of aging, social phobia, attention deficit hyperactivity disorder, disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, sexual dysfunction in males, sexual dysfunction in females, anorexia nervosa, disorders of sleep, autism, seizure disorders, epilepsy, mutism, spinal cord injury, damage of the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, and type II diabetes.
- 57. A method for treating female sexual dysfunction (FSD) comprising the step of administering to a female in need thereof a therapeutically effective amount of a compound of claim 1.
- 58. The method of claim 57 further comprising the step of administrating one or more additional active agents for treating FSD.
- 59. The method of claim 58 wherein said one or more additional active agents is selected from the group consisting of (1) as estrogen receptor modulators, estrogen agonists, estrogen antagonists or combinations thereof; (2) testosterone replacement agent, testosternone (Tostrelle), dihydrotestosterone, dehydroepiandrosterone (DHEA), a testosterone implant, or combinations thereof; (3) estrogen, a combination of estrogen and medroxyprogesterone or medroxyprogesterone acetate (MPA), or estrogen and methyl testosterone hormone replacement therapy agent; (4) one or more dopaminergic agents; (5) one or more of an NPY (neuropeptide Y) inhibitor; (6) one or more of a melanocortin receptor agonist or modulator or melanocortin enhancer; (7) one or more of an NEP inhibitor; (8) one or more of a PDE inhibitor; and (9) one or more of a bombesin receptor antagonist or modulator.
- 60. The method of claims 57, 58 or 59 wherein said FSD is female sexual arousal disorder (FSAD), female orgasmic disorder (FOD), hypoactive sexual desire disorder (HSDD), or sexual pain disorder.
- 61. A method for treating male erectile dysfunction (MED) comprising the step of administering to a male in need thereof a therapeutically effective amount of a compound of claim 1.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Serial No. 60/299,953 filed on Jun. 21, 2001 and incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60299953 |
Jun 2001 |
US |