US 5,552,422 AGranted

Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents

AssigneeMerck Frosst Canada, Inc.

InventorsJacques Y. Gauthier, Cheuk K. Lau, Yves LeBlanc, Chun-Sing Li, Patrick Roy, Michel Therien, Zhaoyin Wang

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Abstract

The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.

Claims21

Dependent claims

A compound of Formula I ##STR46## or a pharmaceutically acceptable salt thereof wherein:

--A--B--D-- is selected from the group consisting of:
(a) --CH.dbd.CH--CH.dbd.,
(b) --CH.dbd.CH--C(OH).dbd.,
(c) --C(OH).dbd.CH--C.dbd.,
(d) --N.dbd.CH--CH.dbd.,
(e) --N.dbd.N--CH.dbd.,
(f) --N.dbd.N--NH--,
(g) --N.dbd.N--N.dbd.,
(h) --N.dbd.CH--NH--,
(i) --N.dbd.CH--N.dbd.,
(j) --CH.dbd.N--NH--,
(k) --CH.dbd.N--N.dbd.,
(l) --CH.dbd.N--CH.dbd.,
(m) --CH.dbd.CH--NH--,
(n) --CH.dbd.CH--N.dbd.,
(o) --S--CH.dbd.CH--,
(p) --O--CH.dbd.CH--,
(q) --CH.dbd.CH--O--,
(r) --CH.dbd.CH--S--,
(s) --CH.dbd.N--S--,
(t) --CH=N--O--,
(u) --N--CH--S--,
(v) --N=CH--O--,
(w) --S--CH=N--,
(x) --O--CH=N--,
(y) --N=N--S--,
(z) --N=N--O--,
(aa) --S--N=N--,
(bb) --O--N=N--and
(cc) --C(OH)=CH--S--;
wherein definitions (a) through (cc) of --A--B--D-- is mono- or di-substituted, the substituents being independently selected from the group consisting of:
(1) hydrogen.
(2) CF.sub.3,
(3) CN,
(4) halo, including F, Cl, Br, I,
(5) C.sub.1-6 alkyl,
X is N, NR.sup.4 O, or S;
R.sup.1 is selected from the group consisting of:
(a) S(O).sub.2 CH.sub.3,
(b) S(O).sub.2 NH.sub.2,
(c) S(O).sub.2 NHCOCF.sub.3,
(d) S(O)(NH)CH.sub.3,
(e) S(O)(NH)NH.sub.2,
(f) S(O)(NH)N HCOCF.sub.3,
(g) P(O)(CH.sub.3)OH, and
(h) P(O)(CH.sub.3)NH.sub.2,
R.sup.2 and R.sup.3 are each independently selected from the group consisting of:
(a) hydrogen,
(b) halo,
(c) C.sub.1-6 alkoxy,
(d) C.sub.1-6 alkylthio,
(c) CN,
(f) C.sub.1-3 fluoroalkyl,
(g) C.sub.1-6 alkyl,
(h) N.sub.3,
(i) --CO.sub.2 H,
(j) --CO.sub.2 --C.sub.1-4 alkyl,
(k) --C(R.sup.5)(R.sup.6)--OH,
(l) --C(R.sup.5)(R.sup.6)--O--C.sub.1-4 alkyl, and
(m) --C.sub.1-6 alkyl--CO.sub.2 --R.sup.7 ;
R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, phenyl and benzyl;
R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of:
(a) hydrogen, and
(b) C.sub.1-6 alkyl.

61 more elements

The compound of claim 15 wherein --A--B--D-- is selected from the group consisting of:

(a) --CH.dbd.CH--CH.dbd.,
(b) --N.dbd.CH--CH.dbd.,
(c) --N.dbd.N--CH.dbd.,
(d) --N.dbd.N--NH--,
(e) --N.dbd.N--N.dbd.,
(f) --N.dbd.CH--NH--,
(g) --N.dbd.CH--N.dbd.,
(h) --CH.dbd.N--NH--,
(i) --CH.dbd.N--N.dbd.,
(j) --CH.dbd.CH--N.dbd.,
(k) --CH.dbd.CH--O--,
(l) --CH.dbd.CH--S--,
(m) --CH.dbd.N--S--,
(n) --N.dbd.CH--S--,
(o) --S--CH.dbd.N--and
(p) --N.dbd.N--S--;
wherein definitions (a) through (p) of --A--B--D-- is mono- or di-substituted, the substituents being independently selected from the group consisting of:
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br and I,
(5) C.sub.1-4 alkyl,
X is N, NR.sup.4 or O;
R.sup.1 is selected from the group consisting of:
(a) S(O).sub.2 CH.sub.3,
(b) S(O).sub.2 NH.sub.2,
(c) S(O)(N H)CH.sub.3,
(d) S(O)(N H)NH.sub.2,
R.sup.2 and R.sup.3 are each independently selected from the group consisting of:
(a) hydrogen,
(b) halo,
(c) C.sub.1-4 alkoxy,
(d) C.sub.1-4 alkylthio,
(e) CN,
(f) C.sub.1-3 fluoroalkyl ,
(g) C.sub.1-4 alkyl,
(h) --C(R.sup.5)(R.sup.6)--O--C.sub.1-4 alkyl, and
R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-4 alkyl, phenyl and benzyl;
R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of:
(a) hydrogen, and
(b) C.sub.1-4 alkyl.

38 more elements

Dependencies are inferred from the claim text.

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Abstract