Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1991-09-30
1994-03-29
Springer, David B.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546176, 546269, 514311, 514337, C07D40506, C07D40512, A61K 3144, A61K 3147
Patent
active
052985121
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention is directed to substituted chromans of the formula (I), depicted below, which by inhibiting 5-lipoxygenase enzyme are useful in the prevention or treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction, stroke and related disease states in mammals. The present invention is also directed to pharmaceutical compositions, and to a method of treatment
Kreft et al., in U.S. Pat. No. 4,661,596, describe compounds which are disubstituted naphthalenes, dihydronaphthalenes or tetralins having the formula ##STR1## wherein the dotted lines represent optional double bonds, R 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 is hydroxy, lower alkoxy, lower alkyl or perfluoro alkyl. These compounds inhibit lipoxygenase enzyme and antagonize the effects of leukotriene D4, and so are useful in the prevention and treatment of asthma.
Eggler et al., in copending International application PCT/US87/02745 filed Oct. 19, 1987 have described similarly active compounds, including chromans of the formula ##STR2## wherein R.sup.x is substantially defined as above, R.sup.z is aryl or heteroaryl, X.sup.a is, for example, oxygen or CH.sub.2, and X.sup.b is C.dbd.O or CHOH. The present compounds generally fail to block leukotriene D4 receptors and so, in this respect, are differentiated from the compounds of Eggler et al., who also report certain structurally related compounds as intermediates (for example, compounds of the formula immediately above wherein R.sup.x is benzyl Many of these intermediates also find utility as intermediates in the present invention.
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 compounds having the structural formula ##STR3## wherein
X is CH.sub.2 or O;
Y and Y.sup.1 are taken together and form a carbonyl group, or Y and Y.sup.1 are taken separately, Y is hydrogen and Y.sup.1 is hydroxy or an acyloxy group which is hydrolyzed to form a hydroxy group under physiological conditions;
R is attached by means of aromatic or heteroaromatic carbon and is phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, pyridazinyl, cinnolinyl, phthalazinyl, pyrimidinyl, naphthyridinyl, pyrrolyl, N-[(C.sub.1 -C.sub.4)alkyl]pyrrolyl, indolyl, N-[(C.sub.1 -C.sub.4)alkyl]indolyl, isoindolyl, N-[(C.sub.1 -C.sub.4)alkyl]isoindolyl, indolizinyl, pyrazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]pyrazolyl, indazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]-1H-indazolyl, 2-[(C.sub.1 -C.sub.4)alkyl]-2H-indazolyl, imidazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]imidazolyl, benzimidazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]benzimidazolyl, furyl, benzofuranyl, isobenzofuranyl, oxazolyl, benzoxazolyl, isoxazolyl, benzo[c]isoxazolyl, benzo[d]isoxazolyl, thienyl, benzothiophenyl, isobenzothienyl, thiazolyl, benzothiazolyl, isothiazolyl, benzo[c]isothiazolyl, or benzo[d]isothiazolyl; or one of said groups which is mono- or disubstituted on carbon with the same or different groups which are bromo, chloro, fluoro, hydroxy, hydroxvmethyl, (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, carboxy, [(C.sub.1 -C.sub.4)alkoxy]carbonyl, or substituted on adjacent carbons with trimethylene, tetramethylene, --CH.sub.2 --O--CH.sub.2 -- or --O-- CH.sub.2 --O--; or substituted on tertiary nitrogen to form an N-oxide; and either, in a first alternative,
R.sup.1 is phenyl, 2-, 3- or 4-pyridyl, 2-, 3-, 4 or 8-quinolyl, 1-, 3- or 4-isoquinolyl, 3- or 4-pyridazinyl, 3- or 4-cinnolinyl, 1-phthalazinyl, 2- or 4-pyrimidinyl, 2- or 4-quinazolinyl, 2-pyrazinyl, 2-quinoxalinyl, 1-, 2- or 3-indolizinyl, 2-, 4- or 5-oxazolyl, 2-benzoxazolyl, 3-, 4- or 5-isoxazolyl, 5-benzo[c]isoxazolyl, 3-benzo[d]isoxazolyl, 2-, 4- or 5-thiazolyl, 2-benzothiazolyl, 3-, 4- or 5-isothiazolyl, 5-benzo[c]isothiazolyl, 3-benzo[d]isothiazolyl, 1-[(C.sub.1 -C.sub.4)alkyl]-2
REFERENCES:
patent: 3419560 (1968-12-01), Bernstein et al.
patent: 3936461 (1976-02-01), Schwender et al.
patent: 4127669 (1978-11-01), Connor et al.
patent: 4563468 (1986-01-01), Batchelor et al.
patent: 4571406 (1986-02-01), Evans et al.
patent: 4642347 (1987-02-01), Kreft, III et al.
patent: 4661596 (1987-04-01), Kreft, III et al.
Eggler James F.
Marfat Anthony
Masamune Hiroko
Melvin, Jr. Lawrence S.
Benson Gregg C.
Olson A. Dean
Pfizer Inc.
Richardson Peter C.
Springer David B.
LandOfFree
Substituted chromans and their use in the treatment of asthma, a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Substituted chromans and their use in the treatment of asthma, a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Substituted chromans and their use in the treatment of asthma, a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-792074