Sulfonamide derivatives of benzenefused hydroxy substituted cycl

Details Sulfonamide derivatives of benzenefused hydroxy substituted cycl Sulfonamide derivatives of benzenefused hydroxy substituted cycl

1995-03-31

1997-06-24

Ivy, C. Warren

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514365, 514367, 514457, 546172, 546173, 548146, 548159, 549 23, 549407, A61K 3135, A61K 3138, C07D31122, C07D33506

Patent

active

056417896

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

The present invention is directed to sulfonamide derivatives of benzenefused, hydroxy substituted allcyclic and heterocyclic compounds. The compounds inhibit the production of leukotrienes and/or block leukotriene receptors and are useful in the prevention or treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction and related disease states in mammals. The present invention is also directed to pharmaceutical compositions comprising said compounds, the use of the compounds in treatment of said disease states and intermediates useful in the synthesis of said compounds of the formula I.
U.S. Pat. No. 4,661,596, refers to compounds which are disubstituted naphthalenes, dihydronaphthalenes or tetralins having the formula ##STR2## wherein the dotted lines represent optional double bonds, R.sup.a is 2-pyridyl, 2-quinolyl, 2-pyrazinyl, 2-quinoxalinyl, 2-thiazolyl, 2-benzothiazolyl, 2-oxazolyl, 2-benzoxazolyl, 1-alkyl-2-imidazolyl or 1-alkyl-2-benzimidazolyl and R.sup.b is hydroxy, lower alkoxy, lower alkyl or perfluoro alkyl.
U.S. Pat. No. 5,059,609 refers to substituted tetralins, chromans and related compounds.
The compounds of these patents are alleged to inhibit lipoxygenase enzyme and antagonize the effects of leukotriene D4 and, therefore, to be useful in the prevention and treatment of asthma.
The chemical nomenclature employed herein generally follows that of "I.U.P.A.C. Nomenclature of Organic Chemistry, 1979 Edition," Pergammon Press, New York, 1979.


SUMMARY OF THE INVENTION

The present invention is directed to racemic or optically active compounds having the structural formula ##STR3## wherein X.sup.1 is hydrogen or OH: Ar is an optionally substituted 5-8 membered heteroaryl or optionally substituted benzene fused optionally substituted heteroaryl ring wherein said heteroaryl ring comprises 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur; CH.dbd.CH, C.tbd.C, CH.sub.2 S, CH.sub.2 SO.sub.2 and CH.sub.2 SO; SO.sub.2 and NR.sup.6 ; optionally substituted (C.sub.1 -C.sub.6)alkyl; (C.sub.3 -C.sub.6) cycloalkyl-(C.sub.1 -C.sub.6)alkyl, optionally halogenated (C.sub.1 -C.sub.6)alkyl and optionally substituted aryl wherein the substituents are selected from the group consisting of optionally halogenated (C.sub.1 -C.sub.6)alkyl, halogen, nitro, carboxyl, N-disubstituted carboxamide, and (C.sub.1 -C.sub.6)alkoxy; (C.sub.1 -C.sub.6)alkyl and halogen, NO.sub.2, CO.sub.2 R and CONR.sub.2 ; wherein each R is independently selected from the group consisting of hydrogen, optionally substituted (C.sub.1 -C.sub.6)alkyl, cycloalkyl-(C.sub.1 -C.sub.6) alkyl, aryl(C.sub.1 -C.sub.6)alkyl and optionally substituted aryl. between 1 and 4; their ease of preparation and valuable biological activity, in the preferred compounds of the formula I, R.sup.1 and R.sup.2 are each hydrogen, X is CH.sub.2 O, Ar is 2-, 3- or 4-pyridyl, quinol-2-yl, 7-chloroquinol-2-yl, 6-fluoroquinol-2-yl, 5-fluorobenzothiazol-2-yl, 5,6-difluorobenzothiazol-2-yl, 5-cyclobutylbenzothiazol-2-yl, 4-isopropylthiazol-2-yl, 4-cyclobutylthiazol-2-yl or pyrazin-2-yl or R.sup.3 is trifluoromethyl, 4-methoxyphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 3-carboxyphenyl, 4-carboxyphenyl, pyrid-2-yl or pyrid-3-yl, optionally halogenated (C.sub.1 -C.sub.6)alkyl or optionally substituted (C.sub.6 -C.sub.10)aryl wherein said substitutents are selected from the group consisting of halo, nitro, (C.sub.1 -C.sub.6)alkyl and (C.sub.1 -C.sub.6)alkoxy.
Preferred compounds of formula I are those wherein Y.sup.1 is O, S, NR.sup.10 or CH.sub.2, wherein R.sup.6 is defined above;
Most preferred are racemic or optically active compounds having the relative stereochemical formulae ##STR4## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.5, Y.sup.1, Ar and n are as described above, most particularly those racemic or optically active compounds of formulae IA, IB, IC and ID wherein Ar is quinol-2-yl, 7-chloroquinol-2-yl, 6-fluoroquinol-2-yl, 5-fluorobenzothiazol-2-yl, or 5,6-difluorobenzothiazol-2-yl, 4-isopropylthiazol-2-y

REFERENCES:
patent: 5059609 (1991-10-01), Eggler
patent: 5395842 (1995-03-01), Labrie

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