Pyridazines as interleukin-1.beta. converting enzyme inhibitors

US6121266A · kind A · utility

Assignee

• Vertex Pharmaceuticals Incorporated · US

Inventors

• Roland E. Dolle · King of Prussia, US
• Denton W. Hoyer · West Haven, US
• Tina Morgan Ross · Limerick, US
• James Rinker · Reading, US
• Stanley J. Schmidt · Chester Springs, US
• Mark A. Ator · Paoli, US

Key dates

• Filing date: May 19, 1995
• Grant date: Sep 19, 2000
• Expiry date: May 19, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D403/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is a halogen, or an oxygen linked leaving group including an aromatic ether, an alkyl sulfonate, an aryl sulfonate, an alkyl phosphonate, an aryl phosphonate, an alkyl phosphate or aryl phosphate; PA1 R.sub.2 is COOR.sub.5, C(.dbd.O)NH(CHR.sub.5).sub.m --COOR.sub.5, NH(CHR.sub.5).sub.m CON(R.sub.5)R.sub.6, C(.dbd.O)N(R.sub.5)R.sub.6 or NH(CHR.sub.5).sub.m OH; PA1 R.sub.3 is H or alkyl; PA1 R.sub.4 is H, substituted or unsubstituted aryl, heteroaryl or alkyl; PA1 R.sub.5 and R.sub.6 are independently H, lower alkyl, aryl, hydroxy alkyl, amino alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycloalkyl; and m=0-6; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1.beta. protease activity in a mammal utilizing the compounds and compositions.