Nicotinamide biaryl derivatives useful as inhibitors of PDE4...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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Reexamination Certificate

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06953810

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; W1is —O—; or —S(═O)t—, where t is 0, 1, or 2; or —N(R3)—; W2is —O—CRARB— or is absent; Y is ═C(R1a)— or —[N→(O)k]— where k is 0 or 1; RAand RBare —H; —F; —CF3; —(C1-C4)alkyl; —(C3-C7) cycloalkyl; phenyl; or benzyl substituted with 0 to 3 substituents R10; or RAand RBare taken together, but only in the case where m is 1, to form a spiro moiety; RCand RDhave the same meaning as RAand RBexcept that one of them must be —H, R1and R2are —H; —F; —Cl; —CN; —NO2; —(C1-C4)alkyl; —(C2-C4)alkynyl; fluorinated-(C1-C3)alkyl; —OR16; and —C(═O)NR22aR22b; R3is —H; —(C1-C3)alkyl; phenyl; benzyl; or —OR16; R4, R5and in addition to other meanings may be taken together to form, e.g.,Q1is 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 Q1is not a discontinuous or restricted biaryl moiety as defined under Q2; where optionally one carbon atom may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; Q2is a discontinuous or restricted biaryl moiety consisting of 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; where optionally one carbon atom may be replaced by a heteroatom selected from N, O, and S; where optionally a second carbon atom thereof, and further optionally a third carbon atom thereof may be replaced by N; Z is selected from:

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