| 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 selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, and pyrazinyl, each optionally fused to phenyl or a monocyclic heteroaryl, and each optionally substituted with one or two substituents Rx; wherein each Rx is independently selected from the group consisting of —F, —Cl, —Br, methyl, methoxy, —CN, —CF3, cyclopropyl, and cyano-cyclopropyl; 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; and B is selected from the group consisting of phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, and pyrazinyl, each optionally substituted with one or two substituents Ry; wherein Ry is independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, methoxy, ethoxy, isopropoxy, —F, —Cl, —Br, —CN, and —CF3, or a pharmaceutically acceptable salt thereof; provided that the compound is not: |
