申请人:Pfizer Inc.
公开号:US05994352A1
公开(公告)日:1999-11-30
Compounds of the formula ##STR1## wherein A, B, D, E, and F are each independently nitrogen or carbon; R.sub.1 is hydrogen, C.sub.1 to C.sub.6 alkyl, --(CH.sub.2).sub.n R.sub.7, or C.sub.1 to C.sub.3 alkyl-aryl; R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, C.sub.1 to C.sub.3 alkyl-aryl, halogen, cyano, nitro, --(CH.sub.2).sub.m NR.sub.8 R.sub.9, --(CH.sub.2).sub.m OR.sub.9, --SR.sub.9, --SO.sub.2 NR.sub.8 R.sub.9, --(CH.sub.2).sub.m NR.sub.8 SO.sub.2 R.sub.9, --(CH.sub.2).sub.m NR.sub.8 CO.sub.2 R.sub.9, --(CH.sub.2).sub.m NR.sub.8 COR.sub.9, --(CH.sub.2).sub.m CONR.sub.7 R.sub.9, or --(CH.sub.2).sub.m CO.sub.2 R.sub.9 ; R.sub.2 and R.sub.3, R.sub.3 and R.sub.4, R.sub.4 and R.sub.5, and R.sub.5 and R.sub.6 may be taken together to form a five- to seven-membered alkyl ring, a six-membered ary ring, a five- to seven-membered heteroalkyl ring, having 1 heteroatom of N, O, or S, or a five- to six-membered heteroaryl ring having 1 or 2 heteroatoms of N, O, or S; R.sub.7 is --OR.sub.10, --SR0.sub.10, --SO.sub.2 NR.sub.10 R.sub.11, --NR.sub.10 SO.sub.2 R.sub.11, --NR.sub.10 CO.sub.2 R.sub.11, --NR.sub.10 COR.sub.11, --CONR.sub.10 R.sub.11, or --CO.sub.2 R.sub.10 ; R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, or C.sub.1 to C.sub.3 alkyl-aryl; m is 0, 1, or 2; n is 2, 3, or 4; and the above aryl groups and the aryl moieties of the above alkyl-aryl groups are each independently phenyl or substituted phenyl, wherein said substituted phenyl may be substituted with one to three of C.sub.1 to C.sub.4 alkyl, halogen, hydroxy, cyano, carboxamido, nitro, or C.sub.1 to C.sub.4 alkoxy, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders and are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.
式为##STR1##的化合物,其中A、B、D、E和F分别独立地为氮或碳;R.sub.1为氢、C.sub.1到C.sub.6烷基、--(CH.sub.2).sub.n R.sub.7,或C.sub.1到C.sub.3烷基-芳基;R.sub.2、R.sub.3、R.sub.4、R.sub.5和R.sub.6分别独立地为氢、C.sub.1到C.sub.6烷基、芳基、C.sub.1到C.sub.3烷基-芳基、卤素、氰基、硝基、--(CH.sub.2).sub.m NR.sub.8 R.sub.9、--(CH.sub.2).sub.m OR.sub.9、--SR.sub.9、--SO.sub.2 NR.sub.8 R.sub.9、--(CH.sub.2).sub.m NR.sub.8 SO.sub.2 R.sub.9、--(CH.sub.2).sub.m NR.sub.8 CO.sub.2 R.sub.9、--(CH.sub.2).sub.m NR.sub.8 COR.sub.9、--(CH.sub.2).sub.m CONR.sub.7 R.sub.9,或--(CH.sub.2).sub.m CO.sub.2 R.sub.9;R.sub.2和R.sub.3、R.sub.3和R.sub.4、R.sub.4和R.sub.5,以及R.sub.5和R.sub.6可以结合在一起形成五至七元烷基环、六元芳环、具有1个N、O或S杂原子的五至七元杂烷基环,或具有1个或2个N、O或S杂原子的五至六元杂芳基环;R.sub.7为--OR.sub.10、--SR0.sub.10、--SO.sub.2 NR.sub.10 R.sub.11、--NR.sub.10 SO.sub.2 R.sub.11、--NR.sub.10 CO.sub.2 R.sub.11、--NR.sub.10 COR.sub.11、--CONR.sub.10 R.sub.11,或--CO.sub.2 R.sub.10;R.sub.8、R.sub.9、R.sub.10和R.sub.11分别独立地为氢、C.sub.1到C.sub.6烷基,或C.sub.1到C.sub.3烷基-芳基;m为0、1或2;n为2、3或4;上述芳基和上述烷基-芳基的芳基基团分别独立地为苯基或取代苯基,其中所述取代苯基可以用C.sub.1到C.sub.4烷基、卤素、羟基、氰基、羧酰胺基、硝基,或C.sub.1到C.sub.4烷氧基取代,并且其药学上可接受的盐。这些化合物在治疗偏头痛和其他疾病方面是有用的,并且是新的。这些化合物是有用的精神治疗药物,是有效的5-羟色胺(5-HT.sub.1)激动剂,可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群头痛、偏头痛、疼痛,以及与血管疾病相关的慢性阵发性半头痛和头痛等疾病,以及由于5-羟色胺神经传导不足而引起的其他疾病。这些化合物还可用作中枢作用降压药和扩血管药。