Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-08-19
1997-01-14
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514365, 548131, 548181, C07D41714, C07D41314, A61K 3140
Patent
active
055940145
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US93/01667 filed Mar. 3, 1993.
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:hydropyridyl-5-substituted-1H-indoles. The compounds are said to have 5-HT.sub.1 receptor agonist and vasoconstrictor activity and to be useful in treating migraine.
European Patent Application Publication Number 35477 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 Application Publication Numbers 438230, 494774, and 497512 refer 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.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula ##STR2## where A represents a direct bond, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl; n is 0, 1, or 2; R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.3 alkylaryl, C.sub.1 -C.sub.3 alkylheteroaryl, or --(CH.sub.2).sub.m R.sub.6 ; W, X, Y, and Z are each independently oxygen, sulfur, nitrogen or carbon, provided that at least one of W, X, Y, or Z is nitrogen; R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are each independently hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.3 alkylaryl, C.sub.1 -C.sub.3 alkylheteroaryl, halogen, cyano, trifluoromethyl, nitro, --OR.sub.7, --NR.sub.7 R.sub.8, --(CH.sub.2).sub.s OR.sub.7, --SR.sub.7, --SO.sub.2 NR.sub.7 R.sub.8, --NR.sub.7 SO.sub.2 R.sub.8, --NR.sub.7 CO.sub.2 R.sub.8, --CONR.sub.7 R.sub.8, or --CO.sub.2 R.sub.7 ; one of R.sub.2 and R.sub.3, R.sub.3 and R.sub.4, or R.sub.4 and R.sub.5 may be taken together to form a five- to seven-membered alkyl ring, a Six-membered aryl 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.6 is cyano, trifluoromethyl, or --OR.sub.9 ; R.sub.7, R.sub.8, and R.sub.9 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, --(CH.sub.2).sub.m R.sub.10, C.sub.1 to C.sub.3 alkylaryl, or aryl; R.sub.7 and R.sub.8 may be taken together to form a C.sub.4 -C.sub.7 alkyl ring; R.sub.10 is cyano, trifluoromethyl, or C.sub.1 -C.sub.4 alkoxy; R.sub.11 is hydrogen, --OR.sub.12, or --NHCOR.sub.12 ; R.sub.12 is C.sub.1 to C.sub.6 alkyl, aryl, or C.sub.1 to C.sub.3 alkyl-aryl; m is 1, 2, or 3; s is 0, 1, 2, or 3; and the above aryl groups and the aryl moieties of the above alkylaryl 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. When R.sub.11 is hydrogen, the epimers with the R abso
REFERENCES:
patent: 4252803 (1981-02-01), Webb
patent: 4839377 (1989-06-01), Bays et al.
patent: 4855314 (1989-08-01), Oxford ert al.
patent: 5208248 (1993-05-01), Baker et al.
patent: 5298491 (1994-03-01), Chauveau
W. Feniuk, et al., P. P. A. Humphrey & M. J. Perren--Br. J. Pharmacol. (1989), 96, 83-90.
P. P. A. Humphrey, et al.,--Br. J. Pharmacol. (1988), 94, 1123-1132.
D. Hoyer, et al., Eur. J. Pharm., 118, 13 (1985).
R. E. Hearing, et al. J. Neuroscience, 7, 894 (1987).
P. Sauerberg, et al. J. Med. Chem., 34, 682 (1991).
G. A. Showell, et al., J. Med. Chem., 34, 1086 (1991).
Macor John E.
Nowakowski Jolanta T.
Fuller Jr. Grover F.
Gerstl Robert
Ginsburg Paul H.
Pfizer Inc
Richardson Peter C.
LandOfFree
Indole derivatives as 5-HT1 agonists does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indole derivatives as 5-HT1 agonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indole derivatives as 5-HT1 agonists will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1388529