5-heteroyl indole derivatives

Details 5-heteroyl indole derivatives 5-heteroyl indole derivatives

1993-08-06

1995-04-25

Ivy, C. Warren

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514318, 514323, 514333, 514365, 514374, 546193, 546201, 546256, 546273, 548202, 548203, 548204, 548205, 548235, C07D41704, A61K 3140

Patent

active

054099412

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/US92/00556 filed Feb. 3, 1992.


FIELD OF THE INVENTION

The present invention relates to 5-heteroyl 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.


BACKGROUND OF THE INVENTION

U.S. Pat. No. 4,839,377 and 4,855,314 and European Patent Application Publication Number 313397 refer to 5-substituted 3-aminoalkyl indoles which are said to be useful for the treatment of migraine. British Patent Application 040279 refers to 3-aminoalkyl-1H-indole-5-thioamides and carboxamides which are said to be useful in treating hypertension and Raynaud's disease and also said to be useful in treating migraine.
British Patent Application 2124210A refers to Sumatriptan [3-(2-dimethylamino)ethyl-N-methyl-1H-indole-5-methane sulphonamide] and its analogs which are said to be useful for the treatment of migraine. European Patent Application Publication Number 303506 refers to 3-poly:hydro-pyridyl-5-substituted-1H-indoles. The compounds are said to be 5-HT.sub.1 -receptor agonists and to have vasoconstrictor activity, as well as 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 be useful in treating cephalic pain and are also said to have 5-HT.sub.1 -receptor agonist and vasoconstrictor activity.


SUMMARY OF THE INVENTION

Compounds of the formula ##STR2## wherein R.sub.1 is hydrogen, C.sub.1 to C.sub.6 alkyl, phenyl, benzyl, --COR.sub.4, or --SO.sub.2 R.sub.4 ; R.sub.2 is ##STR3## R.sub.4 is C.sub.1 to C.sub.6 alkyl, phenyl, or benzyl; R.sub.5 is hydrogen or C.sub.1 to C.sub.6 alkyl; R.sub.6, R.sub.7 R.sub.11, R.sub.12, and R.sub.13 are each independently hydrogen or C.sub.1 to C.sub.6 alkyl; either R.sub.8 or R.sub.9 is hydrogen, C.sub.1 to C.sub.6 alkyl, halogen-substituted C.sub.1 to C.sub.6 alkyl, 1-pyrrolidynylmethyl, 1-piperidynylmethyl, cyclopentylmethyl, cyclohexylmethyl or ##STR4## with the other being the bond between R.sub.3 and Z; Q is ##STR5## R.sub.10 is hydrogen, hydroxy, halogen, cyano, nitro, --CF.sub.3, --NR.sub.11 R.sub.12, C.sub.1 to C.sub.6 alkyl, or --O--(CH.sub.2).sub.b --CH.sub.3 ; X is S, O, or S.fwdarw.O; Y is a covalent bond, C.sub.1 to C.sub.5 alkyl, S, O, ##STR6## --N--(CH.sub.2).sub.c --CH.sub.3, *--(CH.sub.2).sub.c --S--(CH.sub.2).sub.f --, *--(CH.sub.2).sub.c --O--(CH.sub.2).sub.f --, ##STR7## *--(CH.sub.2).sub.c --NR.sub.13 --(C.dbd.O)--, or *--(CH.sub.2).sub.c --NR.sub.13 --SO.sub.2 -- wherein the * in the foregoing groups indicates the point of attachment to the methylene moiety; b, d, and f are each independently 0, 1, 2, or 3; a is 1, 2, or 3; and c is 0, 1 or 2, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders.
Unless otherwise indicated, the alkyl groups referred to herein, as well as the alkyl moieties of other groups referred to herein (e.g. alkoxy), may be linear or branched, and they may also be cyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl) or be linear or branched and contain cyclic moieties.
The following compounds are particularly preferred:
2-[3-(N,N-dimethylaminoethyl)indol-5-yl]-4-(phenylaminomethyl)thiazole;
2-[3-(N,N-dimethylamino)indol-5-yl]-4-(benzylaminomethyl)thiazole;
2-[3-(N,N-dimethylaminoethyl)indol-5-yl]-4-(phenylthiomethyl)thiazole;
2-[3-(N,N-dimethylaminoethyl)indol-5-yl]-4-(phenoxymethyl)thiazole;
2-[3-(N,N-dimethylaminoethyl)indol-5-yl]-4-(2-methoxyphenylaminomethyl)thia zole;
2-[3-(N,N-dimethylaminoethyl)indol-5-yl]-4-(3-methoxyphenylaminomethyl)thia zole;
2-[3-(N,N-dimethylaminoethyl)indol-5-yl]-4-(4methoxyphenylaminomethyl)thiaz ole;
2-[3-(1,2,5,6-tetrahydropyrid-4-yl)indol-5-yl]thiazole,
2-[3-(1,2,5,6-tetrahydropyrid-4-yl)indol-5-yl]-4-methylthiazole;
4-[3-(1,2,5,6-tetrahydropyrid-4-yl)indol-5-yl]-2-methylthiazo

REFERENCES:
patent: 4833153 (1989-05-01), Dowle et al.

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