Ether derivatives useful as inhibitors of pde4 isozymes

Abstract

This application is directed to compounds of the formula wherein j is 1; k is 0 or 1; m is 1, 2 or 3; n is 1 or 2; Wand Ware independently —O— or —S(═O)—, where t is 0, 1, or 2; Y is ═C(R)—, where Ris a member selected from the group consisting of H; F; Cl; CN; NO; —(C–C)alkyl; —(C–C)alkynyl; fluorinated-(C–C)alkyl; fluorinated-(C–C)alkoxy; —OR; and —C(═O)NRR; Rand Rare defined as set forth in the specification; —Rand Rare each a member independently selected from the group consisting of H; F; CF; —(C–C)alkyl; —(C–C)cycloalkyl; phenyl; and benzyl; wherein said cycloalkyl, phenyl, and benzyl moieties are each independently substituted with 0 to 3 substituents R, which is defined as set forth in the specification; Rand Rare defined as set forth in the specification; —Rand Rhave the same meaning as defined above for Rand Rexcept that one of them must be —H, and they are selected independently of each other and of Rand R; Rand Rare each a member independently selected from the group consisting of H; F; Cl; CN; NO; —(C–C)alkyl; —(C–C)alkynyl; fluorinated-(C–C)alkyl; OR; and —C(═O)NRR; —Ris H; —(C–C)alkyl; phenyl; benzyl; or OR; R, R, and Rare defined as set forth in the specification; Jand Jare each independently a moiety comprising a saturated or unsaturated six-membered monocyclic carbon ring; and D is a member independently selected from the group consisting of partial Formulas (1.1.1) through (1.1.5) as set forth in the specification; a pharmaceutically acceptable salt thereof; which are 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.