Nicotinamide biaryl derivatives useful as inhibitors of PDE4 isozymes

US6953810B2 · kind B2 · utility

Assignee

• PFIZER INC. · US

Inventors

• Robert J. Chambers · Mystic, US
• Anthony Marfat · Mystic, US
• Thomas Victor Magee · Mystic, US

Key dates

• Filing date: Jul 2, 2003
• Grant date: Oct 11, 2005
• Expiry date: Dec 21, 2023

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D405/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructuive pulmonary disease, of the formula: where j is 0 or 1 provided that when j is 0, n must be 2; k is 0 or 1; m is 0, 1, or 2; n is 1 or 2; W1 is —O—; or —S(═O)t—, where t is 0, 1, or 2; or —N(R3)—; W2 is —O—CRARB— or is absent; Y is ═C(R1a)— or —[N→(O)k]— where k is 0 or 1; RA and RB are —H; —F; —CF3; —(C1-C4)alkyl; —(C3-C7) cycloalkyl; phenyl; or benzyl substituted with 0 to 3 substituents R10; or RA and RB are taken together, but only in the case where m is 1, to form a spiro moiety; RC and RD have the same meaning as RA and RB except that one of them must be —H, R1 and R2 are —H; —F; —Cl; —CN; —NO2; —(C1-C4)alkyl; —(C2-C4)alkynyl; fluorinated-(C1-C3)alkyl; —OR16; and —C(═O)NR22aR22b; R3 is —H; —(C1-C3)alkyl; phenyl; benzyl; or —OR16; R4, R5 and in addition to other meanings may be taken together to form, e.g., Q1 is a saturated or unsaturated carbon ring system that is a 3- to 7-membered monocyclic, or that is a 7- to 12-membered, fused polycyclic; provided that Q1 is not a discontinuous or …