Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-09-16
1998-05-05
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514339, 514340, 514341, 514342, 514369, 514386, 514389, 514397, 514415, 5462697, 5462714, 5462771, 548182, 548183, 548226, 548229, 548231, 548232, 5483121, 548467, 548504, 548543, A61K 3140, C07D41314
Patent
active
057475016
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to indole derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. The active compounds of the present invention are useful in treating migraine and other disorders.
U.S. Pat. Nos. 4,839,377 and 4,855,314 and European Patent Application Publication Number 313397 refer to 5-substituted 3-aminoalkyl indoles. The compounds are said to be useful for the treatment of migraine.
British Patent Application 040279 refers to 3-aminoalkyl-1H-indole-5-thioamides and carboxamides. The compounds are said to be useful in treating hypertension, Raymond's disease and migraine.
European Patent Application Publication Number 303506 refers to 3-poly:hydro-pyridyl-5-substituted-1H-indoles. The compounds are said to have 5-HT, receptor agonist and vasoconstrictor activity and to be useful in treating migraine.
European Patent Application Publication Number 354777 refers to N-piperidinyl:indolyl:ethyl-alkane sulfonamide derivatives. The compounds are said to have 5-HT.sub.1 receptor agonist and vasoconstrictor activity and to be useful in treating cephalic pain.
European Patent Applications Publication Numbers 438230, 494774, and 497512 refers to indole-substituted five-membered heteroaromatic compounds. The compounds are said to have 5-HT.sub.1 -like receptor agonist activity and to be useful in the treatment of migraine and other disorders for which a selective agonist of these receptors is indicated.
International Patent Application PCT/GB91/00908 and European Patent Application No. 313397A refers to 5-heterocyclic indole derivatives. The compounds are said to exhibit properties useful in the treatment and prophylaxis of migraine, cluster headache, and headache associated with vascular disorders. These compounds are also said to have "5-HT.sub.1 -like" receptor agonism.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula ##STR3## where W is ##STR4## 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 three- to seven-membered alkyl ring or a three- to seven-membered heteroalkyl ring having 1 heteroatom of O; 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; Q is C.sub.1 to C.sub.3 alkyl; 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 (e.g., fluorine, chlorine bromine or iodine), 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.
The compounds of the invention include all optical isomers of formula I (e.g., R and S stereogenicity at any chiral site) and their racemic, diastereomeric, or epimeric mixtures. The epimers with the S absolute configuration at the chiral carbon site designated by # in formula
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Macor John Eugene
Wythes Martin James
Daus Donald G.
Fuller Jr. Grover F.
Ginsburg Paul H.
Pfizer Inc.
Richardson Peter C.
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