Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-05-30
1999-06-01
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142222, 5142272, 5142278, 514252, 514256, 514274, 514278, 514359, 514381, 514383, 514397, 514406, 514407, 544 3, 544 55, 544 585, 544 60, 544333, 544405, 5462721, A61K 31415, C07D23112, C07D40504, C07D40509
Patent
active
059088524
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is in the field of anti-inflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating inflammation and inflammation-associated disorders, such as arthritis.
BACKGROUND OF THE INVENTION
Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of anti-inflammatory drug discovery. However, common non-steroidal anti-inflammatory drugs (NSAIDs) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAIDs can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAIDs is the use of corticosteroids, which have even more drastic side effects, especially when long term therapy is involved.
Previous NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated with inflammation (named "cyclooxygenase II (COX II)" or "prostaglandin G/H synthase II") provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects.
Pyrazole compounds have been used in the treatment of inflammation. U.S. Pat. No. 5,134,142 to Matsuo et al describes 1,5-diaryl pyrazoles, and more particularly, as having anti-inflammatory activity.
U.S. Pat. No. 4,146,721 to Rainer describes 1,3,5-triphenyl pyrazoles as useful analgesics, anti-inflammatory agents and antipyretics, and specifically describes 1,3,5-triphenyl-pyrazol-4-acetamide.
U.S. Pat. No. 3,254,093 to Huisgen et al describes a process for preparing
The synthesis of a series of and specifically l-1-yl!benzenesulfonamide. The synthesis of a series of related triazole et al, Pak. J. Sci. Ind. Res., 35, 428 (1992)!. as an intermediate in the synthesis of the corresponding Chem., 27B, 245 (1988)!. An intermediate for antidiabetic agents, condensation of sulfamylphenylhydrazines with chalcones to produce Res., 35, 8 (1992)!. Specifically, Pharm. Sci., 70, 606 (1981)!.
DESCRIPTION OF THE INVENTION
A class of compounds useful in the treatment of inflammation-related disorders is defined by Formula I: ##STR2## wherein R.sup.1 is alkylsulfonyl or sulfamyl; wherein R.sup.2 is aryl or heterocyclic; wherein R.sup.2 is optionally substituted at a substitutable position with one or more radicals selected from halo, alkoxy, alkyl, nitro, alkylthio, amino, haloalkyl, hydroxyl, carboxyl, N-monoalkylamino, N,N-dialkylamino, cyano, alkoxycarbonyl and acylamino; wherein R.sup.3 is selected from hydrido, alkyl, haloalkyl, cyano, carboxyl, alkoxycarbonyl, amino, acyl, acylamino, halo and alkylsulfonylamino; wherein R.sup.4 is aryl or heterocyclic; wherein R.sup.4 is optionally substituted at a substitutable position with one or more radicals selected from halo, alkoxy, alkyl, nitro, alkylthio, amino, haloalkyl, hydroxyl, carboxyl, N-monoalkylamino, N,N-dialkylamino, cyano, alkoxycarbonyl and acylamino; provided at least one of R.sup.2 and R.sup.4 cannot be phenyl or substituted triazole, when R.sup.1 is sulfamyl; further provided R.sup.2 cannot be 4-methoxyphenyl or 4-methylphenyl when R.sup.4 is 4-methoxyphenyl or 4-methylphenyl, and when R.sup.1 is sulfamyl; and further provided that R.sup.2 cannot be tetrazole when R.sup.4 is fluorophenyl, and when R.sup.1 is methylsulfonyl; or a pharmaceutically-acceptable salt thereof.
The phrase "further provided", as used in the above description, is intended to mean that the denoted proviso is not to be considered conjunctive with any of the other provisos.
Compounds of Formula I would be useful for, but not limited to, t
REFERENCES:
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patent: 4146721 (1979-03-01), Rainer
patent: 5134142 (1992-07-01), Matsuo et al.
patent: 5401765 (1995-03-01), Lee
patent: 5434178 (1995-07-01), Talley et al.
patent: 5466823 (1995-11-01), Talley et al.
patent: 5475018 (1995-12-01), Lee et al.
H. Faidallah et al, Pak. J. Sci. Ind. Res., 35, 213 (1992).
H. Mokhtar et al, Pak. J. Sci. Ind. Res., 35, 428 (1992).
H. Faid-Allah et al, Ind. J. Chem., 27B, 245 (1988).
R. Soliman et al, J. Pharm. Sci., 76, 626 (1987).
H. Faidallal et al, Pak. J. Sci. Ind. Res., 35, 8 (1992).
R. Soliman et al, J. Pharm. Sci., 70, 606 (1981).
Chemical Abstracts, 121:11 (1994).
Penning Thomas D.
Rogier, Jr. Donald J
Talley John J
Yu Stella S
Bulock Joseph W.
G. D. Searle & Co.
Raymond Richard L.
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