Pfizer Corporation

Other

John Eugene Macor

Martin James Wythes

Bertrand Leo Chenard

Jolanta T Nowakowski

Harry Ralph Howard

Harry R Howard, Jr

Kishor A Desai

Jeffrey S Sprouse

Kevin D Shenk

David W Schulz

Indole derivatives as 5-HT1 agonists

Indole derivatives

Indole derivatives as 5-HT1  agonists

The present invention relates to compounds of the formula

4-indole derivatives as serotonin agonists and antagonists

Compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.23, R.sup.24, R.sup.25 and R.sup.26 are defined as in the specification. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and antagonists.

Aryl and heteroaryl alkoxynaphthalene derivatives

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.

##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.8, --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, --SR.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.

5-arylindole derivatives

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.

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, --SR.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.

Growing community of inventors

Salem, CT, United States of America

John Eugene Macor