Substituted pyridines as selective cyclooxygenase-2 inhibitors
AssigneeMerck Frosst Canad, Inc.
InventorsDaniel Dube, Richard Friesen, Rejean Fortin, Zhaoyin Wang, Jacques Yves Gauthier
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Abstract
The invention encompasses the novel compound of Formula I as well as a method of treating COX-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 COX-2 mediated diseases comprising compounds of Formula I.
Claims19
A compound of formula I ##STR60## wherein:
- R.sup.1 is selected from the group consisting of:
- (a) CH.sub.3,
- (b) NH.sub.2,
- (c) NHC(O)CF.sub.3 and
- (d) NHCH.sub.3 ;
- Ar is a mono-, di-, or trisubstituted pyridinyl or pyridinyl N-oxide, wherein the substituents are 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) C.sub.1-6 allyl,
- (g) C.sub.1-6 fluoroalkyl,
- (h) N.sub.3,
- (i) --CO.sub.2 R.sup.3,
- (j) hydroxy,
- (k) --C(R.sup.4)(R.sup.5)--OH,
- (l) --C.sub.1-6 alkyl-CO.sub.2 --R.sup.6 and
- (m) C.sub.1-6 fluoroalkoxy;
- R.sup.2 is selected from the group consisting of:
- (a) halo,
- (b) C.sub.1-6 alkoxy,
- (c) C.sub.1-6 alkylthio,
- (d) C.sub.1-6 alkyl,
- (e) N.sub.3,
- (f) --CO.sub.2 H,
- (g) hydroxy,
- (h) C.sub.1-6 fluoroalkoxy,
- (i) NO.sub.2,
- (j) NR.sup.11 R.sup.12 and
- (k) NHCOR.sup.13 ;
- R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.11, R.sup.12, R.sup.13, are each independently selected from the group consisting of:
- (a) hydrogen and
- (b) C.sub.1-6 alkyl,
- or R.sup.4 and R.sup.5 or R.sup.11 and R.sup.12 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms.
A compound of formula Ic ##STR61## wherein:
- R.sup.1 is selected from the group consisting of:
- (a) CH.sub.3
- (b) NH.sub.2,
- R.sup.2 is selected from the group consisting of:
- (a) chloro and
- (b) methyl,
- and wherein there may be one, two or three groups X 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.1-4 alkyl and
- (g) CF.sub.3.
A compound of formula Ic wherein:
- ##STR62## R.sup.1 is CH.sub.3 or NH.sub.2 ;
- R.sup.2 is selected from the group consisting of:
- (a) halo,
- (b) C.sub.1-6 alkoxy,
- (c) C.sub.1-6 alkylthio,
- (d) C.sub.1-6 alkyl,
- (e) N.sub.3,
- (f) --CO.sub.2 H,
- (g) hydroxy,
- (h) C.sub.1-6 fluoroalkoxy,
- (i) NO.sub.2,
- (j) NR.sup.11 R.sup.12 and
- (k) NHCOR.sup.13, and
- X is hydrogen.
A compound having the name 5-chloro-3-(4-methylsulfonyl)phenyl-2-(3-pyridinyl)pyridine or a pharmaceutically acceptable salt thereof.
A compound having the name 5-chloro-3-(4-methylsulfonyl)phenyl-2-(2-ethyl-5-pyridinyl)pyridine or a pharmaceutically acceptable salt thereof.
A compound of the formula wherein:
- ##STR63## R.sup.1 is CH.sub.3 or NH.sub.2, R.sup.2 is selected from the group consisting of:
- (a) halo,
- (b) C.sub.1-3 alkoxy,
- (c) C.sub.1-3 alkylthio,
- (d) C.sub.1-3 alkyl,
- (e) N.sub.3,
- (f) --CO.sub.2 H,
- (g) hydroxy,
- (h) C.sub.1-3 fluoroalkoxy,
- (i) NO.sub.2,
- (j) NR.sup.11 R.sup.12 and
- (k) NHCOR.sup.13, and
- X is methyl, ethyl, n-propyl, i-propyl or cyclopropyl.
Dependencies are inferred from the claim text.