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US 5,521,213 AGranted
Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2
AssigneeMerck Frosst Canada, Inc.
InventorsPetpiboon Prasit, Daniel Guay, Zhaoyin Wang, Serge Leger, Michel Therien
Life of this patent
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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.
Claims12
A compound of Formulae Ic or Id ##STR62## or a pharmaceutically acceptable salt thereof wherein:
- --A--B--C--D-- is selected from the group consisting of:
- (a) --C(R.sup.7).sub.2 --O--C(O)--,
- (b) --C(O)--O--C(R.sup.7).sub.2 --,
- (c) --O--C(O)--C(R.sup.7).sub.2 --, and
- (d) --C(R.sup.7).sub.2 --C(O)--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).sub.2 NHCOCF.sub.3,
- (d) S(O)(NH)CH.sub.3,
- (e) S(O)(NH)NH.sub.2,
- (f) S(O)(NH)NHCOCF.sub.3,
- (g) P(O)(CH.sub.3)OH, and
- (h) P(O)(CH.sub.3)NH.sub.2,
- R.sup.2 is selected from the group consisting of
- (a) C.sub.3-7, cycloalkyl,
- (b) mono- or di-substituted phenyl or naphthyl wherein the substituent is selected from the group consisting of
- (1) hydrogen,
- (2) halo, including F, Cl, Br, I
- (3) C.sub.1-6 alkoxy,
- (4) C.sub.1-6 alkylthio,
- (5) CN,
- (6) CF.sub.3,
- (7) C1-6alkyl,
- (8) N.sub.3,
- (9) --CO.sub.2 H,
- (10) --CO.sub.2 --C.sub.1-4 alkyl,
- (11) --C(R.sup.5)(R.sup.6)--OH,
- (12) --C(R.sup.5)(R.sup.6)--O--C.sub.1-4 alkyl, and
- (13) --C.sub.1-6 alkyl--CO.sub.2 --R.sup.7 ;
- R.sup.3 and R.sup.4 are the substituent residing on any position of --A--B--C--D-- and are selected independently from the group consisting of:
- (a) hydrogen,
- (b) CF.sub.3,
- (c) CN,
- (d) C1-6alkyl,
- (e) --Q.sup.1 wherein Q.sup.1 is Q.sup.2, CO.sub.2 H, C(R.sup.5)(R.sup.6)OH,
- (f) --O--Q.sup.2,
- (g) --S--Q.sup.2, and
- (h) optionally substituted
- (1) --C.sub.1-5 alkyl-Q.sup.1,
- (2) --O--C.sub.1-5 alkyl-Q.sup.1,
- (3) --S--C.sub.1-5 alkyl-Q.sup.1,
- (4) --C.sub.1-3 alkyl-O--C.sub.1-3 alkyl-Q.sup.1,
- (5) --C.sub.1-3 alkyl-S--C.sub.1-3 alkyl-Q.sup.1,
- (6) --C.sub.1-5 alkyl-O--Q.sup.2,
- (7) --C.sub.1-5 alkyl-S--Q.sup.2,
- wherein the substituent resides on the alkyl chain and the substituent is C.sub.1-3 alkyl, Q.sup.2 is CO.sub.2 --C.sub.1-4 alkyl, tetrazolyl-5-yl, or C(R.sup.5)(R.sup.6)O--C.sub.1-4 alkyl;
- R.sup.5, R.sup.6 and R.sup.7 are each independently selected from the group consisting of
- (a) hydrogen,
- (b) C.sub.1-6 alkyl.
47 more elements
A compound selected from
- (a) 2-(4-Fluorophenyl)-3-(4-(methylsulfonyl)phenyl)-4H-thieno [2,3-c]furan-6-one,
- (b) 2-(3,4-Difluorophenyl)-3-(4-(methylsulfonyl)-phenyl)-4H-thieno 8 2,3-c]furan-6-one,
- (c) 2-(4-Fluorophenyl)-3-(4-(aminosulfonyl)phenyl)-4H-thieno [2,3-c]furan-6-one,
- (d) 2-(3,4-Difluorophenyl)-3-(4-(aminosulfonyl)phenyl)-4H-thieno [2,3-c]furan-6-one,
- (e) 2-(4-(methylsulfonyl)phenyl)-3-phenyl-4H-thieno [2,3-c]furan-6-one,
- or a pharmaceutically acceptable salt thereof.
3 more elements
A compound which is
- 2-(4-(methylsulfonyl)phenyl)-3-phenyl-4H-thieno[2,3-c]furan-6-one,
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.