Nitric oxide releasing prodrugs of diaryl-2-(5h)-furanones as cyclooxygenase-2 inhibitors
AssigneeMerck Frosst Canada, Inc.
InventorsCarl Berthelette, Lianhai Li, Christian Beaulieu, Zhaoyin Wang, Claudio F. Sturino
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Abstract
The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions and methods for treating cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I. The above compounds may be used as a combination therapy with low-dose aspirin to treat chronic cyclooxygenase-2 mediated diseases or conditions while also reducing the risk of thrombotic cardiovascular events.
Claims15
A compound of Formula I
- or a pharmaceutically acceptable salt thereof, wherein:
- n is an integer from 1 to 6;
- R1 is selected from the group consisting of:
- (a) S(O)2CH3 and
- (b) S(O)2NH2,
- R2 and R3 each are independently selected from the group consisting of:
- (a) hydrogen,
- (b) halo,
- (c) C1-6alkoxy,
- (d) C1-6alkylthio,
- (e) CN,
- (f) CF3,
- (g) C1-6alkyl, and
- (h) N3;
- R4 is selected from the group consisting of
- (a) C1-4alkyl, optionally substituted with 1 to 3 halo groups,
- (b) phenyl, naphthyl or a 5- or 6-membered aromatice heterocycle, each optionally substituted with 1 to 3 halo groups,
- (c) —O—R5, and
- (b) —(CH2)m—N(R6)(R7);
- m is an integer from 1 to 4;
- and
- R5, R6 and R7 are each independently selected from the group consisting of hydrogen and C1-4alkyl, optionally substituted with 1 to 3 halo groups.
Dependencies are inferred from the claim text.