申请人:——
公开号:US20040259890A1
公开(公告)日:2004-12-23
Compounds of the formula (I):
1
(wherein
A is an optionally substituted straight-chain hydrocarbon having 1 to 6 carbon atoms, which is optionally intervened by oxygen or nitrogen atom;
Ar
1
is aryl or heteroaryl, any of which is optionally substituted;
n is 0 or 1;
R
0
is hydrogen, or lower alkylene attached to an arbitrary, bondable position of A;
T, U, V and W are independently nitrogen atom or optionally substituted methine, and at least two of T, U, V and W are said methine group;
X is —N(SO
2
R
1
)—, —N(COR
2
)— or —CO—;
Y is —C(R
3
)(R
4
)—, —O— or —N(R
5
)—;
Z is methine or nitrogen atom) exhibit NPY antagonistic activities and are useful as agents for the treatment of various diseases related to NPY, for example, cardiovascular disorders such as hypertension, nephropathy, heart disease, vasospasm, arteriosclerosis, etc., central nervous system disorders such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal, circadian rhythm disorders, schizophrenia, etc., metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia, etc., sexual and reproductive dysfunctions, and gastro-intestinal motility disorder.
化合物的结构式为(I):1(其中A是具有1到6个碳原子的直链烃基,可以是选用的取代基,也可以由氧或氮原子插入;Ar1是芳基或杂环芳基,任何一种都可以是选用的取代基;n为0或1;R0为氢或连接到A的任意可结合位置的低碳烷基;T、U、V和W分别是氮原子或选用的甲烷基,其中至少两个是甲烷基;X为—N(SO2R1)—、—N(COR2)—或—CO—;Y为—C(R3)(R4)—、—O—或—N(R5)—;Z为甲烷基或氮原子),具有NPY拮抗活性,并可用作治疗与NPY相关的各种疾病的药物,例如心血管疾病如高血压、肾病、心脏病、血管痉挛、动脉硬化等,中枢神经系统疾病如贪食症、抑郁症、焦虑症、癫痫、痴呆、疼痛、酗酒、戒毒、昼夜节律紊乱、精神分裂症等,代谢疾病如肥胖症、糖尿病、激素异常、高胆固醇血症、高脂血症等,性和生殖功能障碍以及胃肠动力障碍。