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:
##STR1##
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.,
##STR2##
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 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; Q2 is 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:
##STR3##
