Stilbene derivatives useful as cyclooxygenase-2 inhibitors
AssigneeMerck Frosst Canada, Inc.
InventorsJoseph Atkinson, Zhaoyin Wang
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Abstract
The invention encompasses novel compounds of Formula Iuseful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1## The invention also encompasses certain pharmaceuticalcompositions and methods for treatment of cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I.
Claims17
A compound of Formula I ##STR61## or pharmaceutically acceptable salts thereof wherein X is
- (a) CH.sub.2 OH,
- (b) CHO,
- (c) CO.sub.2 H, or
- (d) CO.sub.2 R.sup.4 ;
- Y is
- (a) CH.sub.2 OH, or
- (b) CH.sub.2 OCOR.sup.5 ;
- 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 NHC(O)CF.sub.3,
- (d) S(O)(NH)CH.sub.3,
- (e) S(O)(NH)NH.sub.2,
- (f) S(O)(NH)NHC(O)CF.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 each are independently selected from the group consisting of
- (a) hydrogen,
- (b) halo,
- (c) C.sub.1-6 alkoxy,
- (d) C.sub.1-6 alkylthio,
- (e) CN,
- (f) CF.sub.3,
- (g) C.sub.1-6 alkyl,
- (h) N.sub.3 ;
- R.sup.4 is selected from the group consisting of
- (a) hydrogen, and
- (b) C.sub.1-6 alkyl;
- R.sup.5 is selected from the group consisting of
- (a) hydrogen,
- (b) C.sub.1-6 alkyl,
- (c) mono- or disubstituted phenyl wherein the substituent is selected from
- (1) hydrogen,
- (2) halo,
- (3) C.sub.1-6 alkyl,
- (4) C.sub.1-6 alkoxy,
- (5) C.sub.1-6 alkylthio,
- (6) OH,
- (7) CN,
- (8) CF.sub.3, and
- (9) CO.sub.2 R.sup.4,
- with the proviso that the compound is other than 2-(4-fluorophenyl)-3-(4-methylsulfonyl)phenyl!-1,4-dihydroxy-2-butene.
A compound selected from the group consisting of
- (a) (Z)-2-(4-(methylsulfonyl)phenyl)-3-phenyl-2-butene-1,4-diol;
- (b) (Z)-2-(4-(methylsulfonyl)phenyl)-3-phenyl-2-butene-1,4-diol, 1-acetate;
- (c) (Z)-4-acetoxy-3-(4-(methylsulfonyl)phenyl)-2-phenyl -2-butenal;
- (d) (Z)-4-acetoxy-3-(4-(methylsulfonyl)phenyl)-2-phenyl -2-butenoic acid;
- and
- (e) (Z)-4-acetoxy-3-(4-(methylsulfonyl)phenyl)-2-phenyl-2-butenoic acid, methyl ester.
A compound of formula Ia ##STR62## wherein the variables R.sup.2, R.sup.3, Y and X are selected from the following table:
- ______________________________________ R.sup.2 R.sup.3 Y X ______________________________________ H H CH.sub.2 OH CH.sub.2 OH H H CH.sub.2 OH CH.sub.2 OAc H H CHO CH.sub.2 OAc H H CO.sub.2 H CH.sub.2 OAc H H CO.sub.2 Me CH.sub.2 OAc H H CH.sub.2 OH CH.sub.2 OCOPh H H CHO CH.sub.2 OCOPh H H CO.sub.2 H CH.sub.2 OCOPh H H CO.sub.2 Me CH.sub.2 OCOPh F F CH.sub.2 OH CH.sub.2 OH F F CH.sub.2 OH CH.sub.2 OAc F F CHO CH.sub.2 OAc F F CO.sub.2 H CH.sub.2 OAc F F CO.sub.2 Me CH.sub.2 OAc H F CH.sub.2 OH CH.sub.2 OH H F CH.sub.2 OH CH.sub.2 OAc H F CHO CH.sub.2 OAc H F CO.sub.2 H CH.sub.2 OAc H F CO.sub.2 Me CH.sub.2 OAc. ______________________________________
A compound of formula Ib ##STR63## wherein the variables R.sup.2, R.sup.3, X and Y are selected from the following table:
- ______________________________________ R.sup.2 R.sup.3 X Y ______________________________________ H H CH.sub.2 OH CH.sub.2 OH H H CH.sub.2 OH CH.sub.2 OAc H H CHO CH.sub.2 OAc H H CO.sub.2 H CH.sub.2 OAc H H CO.sub.2 Me CH.sub.2 OAc H H CH.sub.2 OH CH.sub.2 OCOPh H H CHO CH.sub.2 OCOPh H H CO.sub.2 H CH.sub.2 OCOPh H H CO.sub.2 Me CH.sub.2 OCOPh F F CH.sub.2 OH CH.sub.2 OH F F CH.sub.2 OH CH.sub.2 OAc F F CHO CH.sub.2 OAc F F CO.sub.2 H CH.sub.2 OAc F F CO.sub.2 Me CH.sub.2 OAc H F CH.sub.2 OH CH.sub.2 OH H F CH.sub.2 OH CH.sub.2 OAc H F CHO CH.sub.2 OAc H F CO.sub.2 H CH.sub.2 OAc H F CO.sub.2 Me CH.sub.2 OAc. ______________________________________
Dependencies are inferred from the claim text.