Pyridazines as interleukin-1&bgr; converting enzyme inhibitors

US6624166B1 · kind B1 · 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: Apr 3, 1996
• Grant date: Sep 23, 2003
• Expiry date: Apr 3, 2016

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: whereinR1 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;R2 is COOR5, C(═O)NH(CHR5)m—COOR5, NH(CHR5)mCON(R5)R6, C(═O)N(R5)R6 or NH(CHR5)mOH;R3 is H or alkyl;R4 is H, sybstituted or unsubstituted aryl, heteroaryl or alkyl;R5 and R6 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&bgr; protease activity in a mammal utilizing the compounds and compositions.