WO2001083434B1 - P-(sulfonyl)-aryl and heteroaryls amines - Google Patents

Abstract

This invention relates to anti-inflammatory and analgesic compounds, especially to certain p-(sulfonyl)phenyl amino derivatives, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds. The claimed compounds have prostaglandin G/H synthase inhibitor activity and are suitable for the treatment of inflammatory diseases, such as myositis, synovitis, rheumatoid arthritis, osteoarthritis, gout, ankylosing spondylitis and bursitis, for the treatment of Alzheimer's disease or of an autoimmune disease such as systemic lupus erythematosus and type I diabetes.

Claims

AMENDED CLAIMS

[received by the International Bureau on 27 December 2001 (27.12.01); original claim 1 amended; remaining claims unchanged (2 pages)]

1. A compound selected from the group of compounds represented by formula

(I):

Formula I wherein:

A is -(CR₂)_π- where n is 1, 2, or 3 and R is independently hydrogen or alkyl; B is aryl or heteroaryl; X and Y are, independently, CH or nitrogen;

R¹ is alkyl, alkenyl, cyanoalkyl, cycloalkyl, cycloalkylalkyl, aryl, alkylthio substituted aryl, alkylsulfonyl substituted aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaralkyl, heteroalkyl or alkylcarbonylalkyl; R² is alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, or NR¹³R¹⁴ wherein:

R¹³ is hydrogen or alkyl;

R¹⁴ is hydrogen, alkyl, alkenyl, acyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, or aminoalkyl; R³ is hydrogen, alkyl, halo, nitro, cyano, hydroxy, alkoxy; and prodrugs, individual isomers, mixtures of isomers, and pharmaceutically acceptable salts thereof; with the proviso that the following compounds are excluded;

4- {N,N-(benzyl)(l-cyclohexyl-4-pyridyl)amino} phenyl 4-methoxyphenyl sulfone; 84

4-{N,N-(3-nitrobenzyl)(l-cyclohexyl-4-pyridyl)amino}phenyl 4-methoxyphenyl sulfone;

4-[N,N-[{ l-(4-cyanophenylmethyl)-5-methyl-imidazol-2-yl}- methyl](cyclopropylmethyl)amino]-2-methyl -phenyl phenyl sulfone; 4-dibenzylamino-benzensulfonamide;

4-[(benzyl)(ethyl)amino]-N-acetyl-benzensulfonamide; 4-[(butyl)(3-phenylpropyl)amino]-3-nitro-N,N-butyl- (phenylpropyl)benzensulfonamide and

4-dibenzylamino-3-methyl-N,N-dimethyl-benzensulfonamide.

2. The compound of Claim 1, wherein:

R¹ is alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, or heteroalkyl; R² is alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, or NR¹³R¹⁴ wherein:

R¹³ is hydrogen or alkyl; R¹⁴ is hydrogen, alkyl, alkenyl, acyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, or aminoalkyl.

The compound of Claim 1 or 2, wherein:

R³ is hydrogen, and at least one of X and Y is CH.

4. The compound of Claim 1, 2 or 3 wherein B is optionally substituted phenyl or heteroalkyl.

5. The compound of any one of Claims 1-4 wherein R¹ is alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl or heteroalkyl. 85 Statement under PCT Article 19(1)

Compound 2T, compound 2AO disclosed in WO 98 01425 A (SCHERING CORP); compound 8e disclosed in CJ. DINSMORE ET AL: BIOLOG. MED. CHEM.; N⁴-dibenzyl- sulphanilamide disclosed in R.D. DESAI ET AL: INDIAN J. PHARM.; compound V disclosed in J.H. BILLMAN ET AL: J. ORG. CHEM.; compound 5 disclosed in A.R. KATRITZKY ET AL: SYNTH. COMMUN.; and compound 631 disclosed in WO 01 17982 A (GLAXO GROUP LTD ET AL) have been disclaimed from original claim 1.