| 摘要 |
The present invention is directed to compounds that modulate the bioactivity of an orexin receptor such as OX1 or OX2, or both; to pharmaceutical compositions and combinations comprising a compound of the invention; to methods of treatment of malconditions in patients wherein modulation of an orexin receptor is medically indicated; and to methods of preparation of compounds of the invention. For example, orexin receptor-modulatory compounds of the present invention can be used in treatment of an eating disorder, obesity, alcoholism or an alcohol-related disorder, drug abuse or addiction including addiction to cocaine, opiates, amphetamines, or nicotine, a sleep disorder, a cognitive dysfunction in a psychiatric or neurologic disorder, depression, anxiety, panic disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, headache, migraine, pain, gastrointestinal diseases, epilepsy, inflammations, immune-related diseases, endocrine-related diseases, cancer, hypertension, behavior disorder, mood disorder, manic depression, dementia, sex disorder, psychosexual disorder, or renal disease. |
| 主权项 |
1. A compound of Formula (VI): wherein R10 is H or methyl; Het2 is a monocyclic heteroaryl comprising one N and one or two additional heteroatoms selected from the group consisting of NH, O, and S;
wherein Het2 is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C1-4alkyl, C1-4alkoxy, —CN, —CF3, and C3-6cycloalkyl, wherein said cycloalkyl is optionally substituted with halo, methyl, or cyano; or two adjacent substituents taken together with the atoms to which they are attached form a fused phenyl or monocyclic heteroaryl; X, Y, and Z are defined as in (a), (b), or (c), wherein:
(a) X is N, Y is CH, and Z is S;(b) X is N, Y is CHCH, and Z is CH; and(c) X is CH, Y is CHCH, and Z is CH; each R11 is independently selected from the group consisting of methyl, cyano, chloro, fluoro, and methoxy; t is 0, 1, or 2; B is phenyl or a monocyclic heteroaryl comprising one N and one or two additional heteroatoms selected from the group consisting of NH, O, and S; wherein ring B is optionally substituted with one or two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, halo, —CN, and —CF3; or a pharmaceutically acceptable salt thereof; or a compound of Formula (VII): wherein R10 is H or methyl; Het2 is a monocyclic heteroaryl comprising one N and one or two additional heteroatoms selected from the group consisting of NH, O, and S;
wherein Het2 is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C1-4alkyl, C1-4alkoxy, —CN, —CF3, and C3-6cycloalkyl, wherein said cycloalkyl is optionally substituted with halo, methyl, or cyano; or two adjacent substituents taken together with the atoms to which they are attached form a fused phenyl or monocyclic heteroaryl; X, Y, and Z are defined as in (a), (b), or (c), wherein:
(a) X is N, Y is CH, and Z is S;(b) X is N, Y is CHCH, and Z is CH; and(c) X is CH, Y is CHCH, and Z is CH; each R11 is independently selected from the group consisting of methyl, cyano, chloro, fluoro, and methoxy; t is 0, 1, or 2; B is phenyl or a monocyclic heteroaryl comprising one N and one or two additional heteroatoms selected from the group consisting of NH, O, and S; wherein ring B is optionally substituted with one or two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, halo, —CN, and —CF3; or a pharmaceutically acceptable salt thereof; or a compound of Formula (IX): wherein Het2 is a monocyclic heteroaryl comprising one N and one or two additional heteroatoms selected from the group consisting of NH, O, and S;
wherein Het2 is optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C1-4alkyl, C1-4alkoxy, —CN, —CF3, and C3-6cycloalkyl, wherein said cycloalkyl is optionally substituted with halo, methyl, or cyano; or two adjacent substituents taken together with the atoms to which they are attached form a fused phenyl or monocyclic heteroaryl; X, Y, and Z are defined as in (a), (b), or (c), wherein:
(a) X is N, Y is CH, and Z is S;(b) X is N, Y is CHCH, and Z is CH; and(c) X is CH, Y is CHCH, and Z is CH; each R11 is independently selected from the group consisting of methyl, cyano, chloro, fluoro, and methoxy; t is 0, 1, or 2; B is phenyl or a monocyclic heteroaryl comprising one N and one or two additional heteroatoms selected from the group consisting of NH, O, and S; wherein ring B is optionally substituted with one or two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, halo, —CN, and —CF3; or a pharmaceutically acceptable salt thereof. |
