Indole derivatives as 5-ht1 agonists

Abstract

Compounds of the formula ##STR1## where W is ##STR2## n is 0, 1, or 2; m is 0, 1, 2, or 3; Y and G are each independently oxygen or sulfur; Z is --O--, --S--, --NH, or --CH.sub.2 ; R.sub.1 is hydrogen, C.sub.1 to C.sub.8 alkyl, substituted C.sub.1 to C.sub.8 alkyl substituted with one hydroxy, C.sub.3 to C.sub.8 alkenyl, C.sub.3 to C.sub.8 alkynyl, aryl, C.sub.1 to C.sub.3 alkylaryl, C.sub.1 to C.sub.3 alkylheteroaryl, or --Q--R.sub.4 ; R.sub.2 and R.sub.3 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, C.sub.1 to C.sub.3 alkylaryl, or C.sub.1 to C.sub.3 alkylheteroaryl; R.sub.4 is cyano, trifluoromethyl, --COR.sub.9, --CO.sub.2 R.sub.9, --CONR.sub.9 R.sub.10, --OR.sub.9, --SO.sub.2 NR.sub.9 R.sub.10, or --S(O).sub.q R.sub.9 ; R.sub.9 and R.sub.10 are each independently hydrogen, C.sub.1 to C.sub.8 alkyl, C.sub.1 to C.sub.3 alkylaryl, aryl, or R.sub.9 and R.sub.10 may together be taken to form a three- to seven-membered alkyl ring or a three- to seven-membered heteroalkyl ring having 1 heteroatom of O; Q is C.sub.1 to C.sub.3 alkyl; R.sub.11 is hydrogen, --OR.sub.12, or --NHCOR.sub.12 ; R.sub.12 is hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, or C.sub.1 to C.sub.3 alkyl-aryl; q is 0, 1, or 2; a first chiral carbon is designated by an asterisk; a second chiral carbon is designated by #; and the above aryl groups and the aryl moieties of the above alkyl-aryl groups are independently selected from phenyl and substituted phenyl, wherein said substituted phenyl may be substituted with one to three groups selected from C.sub.1 to C.sub.4 alkyl, halogen, hydroxy, cyano, carboxamido, nitro, and C.sub.1 to C.sub.4 alkoxy, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders 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.