Oxime and/or hydrazone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use

1 . A compound of Formula (II), or a pharmaceutically acceptable salt thereof;

wherein the compound of Formula (II) is:

wherein:

A-B is:

(a) N—C;

(b) C—N; or

(c) N—N;

when sides d and f are double bonds, and sides e and g are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) ═N—CR 4 ═CR 4 ′—;

(b) ═N—CR 4 ═N—;

(c) ═CR 4 —N═CR 4 ′—;

(d) ═CR 4 —N═N—;

(e) ═N—N═CR 4 —; or

(f) ═N—N═N—;

R 2 and R 2′ , as defined herein taken together are:

or R 2′ and R 5 , as defined herein, taken together with the carbon atoms to which they are attached are a cycloalkyl group or a heterocyclic ring;

R 97 is:

(a) hydrogen;

(b) alkylthio;

(c) alkylsulfinyl;

(d) alkylsulfonyl;

(e) cyano;

(f) carboxyl;

(g) amino;

(h) lower alkyl;

(i) haloalkyl;

(j) hydroxy;

(k) alkoxy;

(l) haloalkoxy;

(m) alkylarylalkylamino;

(n) aminoalkyl;

(o) aminoaryl;

(p) sulfonamido;

(q) alkylsulfonamido;

(r) arylsulfonamido;

(s) heterocyclic ring;

(t) hydroxyalkyl; or

(u) nitro;

a is an integer from 1 to 3;

when sides e and g are double bonds, and sides d and f are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) —CR 4 ═N—N═;

(b) —N═N—CR 4 ═;

(c) —CR 4 ═N—CR 4 ′═;

(d) —N═CR 4 —N═;

(e) —CR 4 ═CR 4 ′—N═;

(f) —N═N—N═;

when side g is a double bond, and sides d, e and f are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) —C(O)—O—CR 4 ═;

(b) —C(Q)—NR 3 —CR 4 ═;

(c) —C(O)—S—CR 4 ═; or

(d) —C(H)R 4 —C(OH)R 5 —N═;

when sides d is a double bond, and sides e, f and g are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) ═CR 4 —O—C(O)—;

(b) ═CR 4 —NR 3 —C(O)—;

(c) ═CR 4 —S—C(O)—; or

(d) ═N—C(OH)R 4 —C(H)R 5 —;

when sides f is a double bond, and sides d, e and g are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) —CH(R 4 )—CR 5 ═N—; or

(b) —C(O)—CR 4 ═CR 5 —;

when sides e is a double bond, and sides d, f and g are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) —N═CR 4 —CH(R 5 )—; or

(b) —CR 4 ═CR 5 —C(O)—;

when sides d, e, f and g are single bonds, —X 2 —Y 2 -Z 2 - is:

(a) —C(O)—CR 4 (R 4′ )—C(O)—;

R 1 is:

(a) —S(O) 2 —CH 3 ;

(b) —S(O) 2 —NR 8 (D 1 );

(c) —S(O) 2 —N(D 1 )—C(O)—CF 3 ;

(d) —S(O)—(NH)—NH(D 1 );

(e) —S(O)—(NH)—N(D 1 )—C(O)—CF 3 ;

(f) —P(O)(CH 3 )NH(D 1 );

(g) —P(O)(CH 3 ) 2 ;

(h) —C(S)—NH(D 1 );

(i) (c) —S(O)(NH)CH 3 ;

(j) —P(O)(CH 3 )OD 1 ; or

(k) —P(O)(CH 3 )NH(D 1 );

R 1′ at each occurrence is independently:

(a) hydrogen;

(b) halogen;

(c) methyl; or

(d) CH 2 OH;

R 2 is:

(a) lower alkyl;

(b) cycloalkyl;

(c) mono-, di- or tri-substituted phenyl or naphthyl, wherein the substituents are each independently:

(1) hydrogen;

(2) halo;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) lower alkyl;

(8) N 3 ;

(9) —CO 2 D 1 ;

(10) —CO 2 -lower alkyl;

(11) —(C(R 5 )(R 6 )) z —OD 1 ;

(12) —(C(R 5 )(R 6 )) z —O-lower alkyl;

(13) lower alkyl-CO 2 —R 5 ;

(14) —OD 1 ;

(15) haloalkoxy;

(16) amino;

(17) nitro;

(18) alkylsulfinyl; or

(19) heteroaryl;

(d) mono-, di- or tri-substituted heteroaryl, wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one heteroatom which is S, O, or N, and, optionally, 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one heteroatom which is N, and, optionally, 1, 2, 3, or 4 additional N atoms; wherein the substituents are each independently:

(1) hydrogen;

(2) halo;

(3) lower alkyl;

(4) alkoxy;

(5) alkylthio;

(6) CN;

(7) haloalkyl, preferably CF 3 ;

(8) N 3 ;

(9) —C(R 5 )(R 6 )—OD 1 ;

(10) —C(R 5 )(R 6 )—O-lower alkyl; or

(11) alkylsulfinyl;

(e) benzoheteroaryl which includes the benzo fused analogs of (d);

(f) —NR 10 R 11 ;

(g) —SR 11 ;

(h) —OR 11 ;

(i) —R 11 ;

(j) alkenyl;

(k) alkynyl;

(l) unsubstituted, mono-, di-, tri- or tetra-substituted cycloalkenyl, wherein the substituents are each independently:

(1) halo;

(2) alkoxy;

(3) alkylthio;

(4) CN;

(5) haloalkyl, preferably CF 3 ;

(6) lower alkyl;

(7) N 3 ;

(8) —CO 2 D 1 ;

(9) —CO 2 -lower alkyl;

(10) —C(R 12 )(R 13 )—OD 1 ;

(11) —C(R 12 )(R 13 )—O-lower alkyl;

(12) lower alkyl-CO 2 —R 12 ;

(13) benzyloxy;

(14) —O-(lower alkyl)-CO 2 R 12 ;

(15) —O-(lower alkyl)-NR 12 R 13 ; or

(16) alkylsulfinyl;

(m) mono-, di-, tri- or tetra-substituted heterocycloalkyl group of 5, 6 or 7 members, or a benzoheterocycle, wherein said heterocycloalkyl or benzoheterocycle contains 1 or 2 heteroatoms selected from O, S, or N and, optionally, contains a carbonyl group or a sulfonyl group, and wherein said substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) —C(R 12 )(R 13 )—OD 1 ;

(9) —C(R 12 )(R 13 )—O-lower alkyl; or

(10) alkylsulfinyl;

(n) styryl, mono or di-substituted styryl, wherein the substituent are each independently:

(1) halo;

(2) alkoxy;

(3) alkylthio;

(4) CN;

(5) haloalkyl, preferably CF 3 ;

(6) lower alkyl;

(7) N 3 ;

(8) —CO 2 D 1 ;

(9) —CO 2 -lower alkyl;

(10) —C(R 12 )(R 13 )—OD 1 ;

(11) —C(R 12 )(R 13 )—O-lower alkyl;

(12) lower alkyl-CO 2 —R 12 ;

(13) benzyloxy;

(14) —O-(lower alkyl)-CO 2 R 12 ; or

(15) —O-(lower alkyl)-NR 12 R 13 ;

(o) phenylacetylene, mono- or di-substituted phenylacetylene, wherein the substituents are each independently:

(1) halo;

(2) alkoxy;

(3) alkylthio;

(4) CN;

(5) haloalkyl, preferably CF 3 ;

(6) lower alkyl;

(7) N 3 ;

(8) —CO 2 D 1 ;

(9) —CO 2 -lower alkyl;

(10) —C(R 12 )(R 13 )—OD 1 ;

(11) —C(R 12 )(R 13 )—O-lower alkyl;

(12) lower alkyl-CO 2 —R 12 ;

(13) benzyloxy;

(14) —O-(lower alkyl)-CO 2 R 12 ; or

(15) —O-(lower alkyl)-NR 12 R 13 ;

(p) fluoroalkenyl;

(q) mono- or di-substituted bicyclic heteroaryl of 8, 9 or 10 members, containing 2, 3, 4 or 5 heteroatoms, wherein at least one heteroatom resides on each ring of said bicyclic heteroaryl, said heteroatoms are each independently O, S and N and said substituents are each independently:

(1) hydrogen;

(2) halo;

(3) lower alkyl;

(4) alkoxy;

(5) alkylthio;

(6) CN;

(7) haloalkyl, preferably CF 3 ;

(8) N 3 ;

(9) —C(R 5 )(R 6 )—OD 1 ; or

(10) —C(R 5 )(R 6 )—O-lower alkyl;

(r) K;

(s) aryl;

(t) arylalkyl;

(u) cycloalkylalkyl;

(v) —C(O)R 11 ;

(u) hydrogen;

(v) arylalkenyl;

(w) arylalkoxy;

(x) alkoxy;

(y) aryloxy;

(z) cycloalkoxy;

(aa) arylthio;

(bb) alkylthio;

(cc) arylalkylthio; or

(dd) cycloalkylthio;

R 3 is:

(a) hydrogen;

(b) haloalkyl, preferably CF 3 ;

(c) CN;

(d) lower alkyl;

(e) —(C(R e )(R f )) p —U—V;

(f) K;

(g) unsubstituted or substituted:

(1) lower alkyl-Q;

(2) lower alkyl-O-lower alkyl-Q;

(3) lower alkyl-S-lower alkyl-Q;

(4) lower alkyl-O-Q;

(5) lower alkyl-S-Q;

(6) lower alkyl-O—V;

(7) lower alkyl-S—V;

(8) lower alkyl-O—K; or

(9) lower alkyl-S—K;

wherein the substituent(s) reside on the lower alkyl group;

(h) Q;

(i) alkylcarbonyl;

(j) arylcarbonyl;

(k) alkylarylcarbonyl;

(l) arylalkylcarbonyl;

(m) carboxylic ester;

(n) carboxamido;

(o) cycloalkyl;

(p) mono-, di- or tri-substituted phenyl or naphthyl, wherein the substituents are each independently:

(1) hydrogen;

(2) halo;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) lower alkyl;

(8) N 3 ;

(9) —CO 2 D 1 ;

(10) —CO 2 -lower alkyl;

(11) —(C(R 5 )(R 6 )) z —OD 1 ;

(12) —(C(R 5 )(R 6 )) z —O-lower alkyl;

(13) lower alkyl-CO 2 —R 5 ;

(14) —OD 1 ;

(15) haloalkoxy;

(16) amino;

(17) nitro; or

(18) alkylsulfinyl;

(q) alkenyl;

(r) alkynyl;

(s) arylalkyl;

(t) lower alkyl-OD 1 ;

(u) alkoxyalkyl;

(v) aminoalkyl;

(w) lower alkyl-CO 2 R 10 ;

(x) lower alkyl-C(O)NR 10 (R 10′ );

(y) heterocyclicalkyl; or

(z) heterocyclic ring-C(O)—;

R 4 , R 4′ , R 5 and R 5′ are each independently:

(a) hydrogen;

(b) amino;

(c) CN;

(d) lower alkyl;

(e) haloalkyl;

(f) alkoxy;

(g) alkylthio;

(h) Q;

(i) —O-Q;

(j) —S-Q;

(k) K;

(l) cycloalkoxy;

(m) cycloalkylthio;

(n) unsubstituted, mono-, or di-substituted phenyl or unsubstituted, mono-, or di-substituted benzyl, wherein the substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) Q;

(9) nitro; or

(10) amino;

(o) unsubstituted, mono-, or di-substituted heteroaryl or unsubstituted, mono-, or di-substituted heteroarylmethyl, wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one heteroatom which is S, O, or N, and, optionally, 1, 2, or 3 additional N atoms; or the heteroaryl is a monocyclic ring of 6 atoms, said ring having one heteroatom which is N, and, optionally, 1, 2, 3, or 4 additional N atoms; said substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) —C(R 6 )(R 7 )—OD 1 ;

(9) —C(R 6 )(R 7 )—O-lower alkyl; or

(10) alkylsulfinyl

(p) —CON(R 8 )(R 8 );

(q) —CH 2 OR 8 ;

(r) —CH 2 OCN;

(s) unsubstituted or substituted:

(1) lower alkyl-Q;

(2) —O-lower alkyl-Q;

(3) —S-lower alkyl-Q;

(4) lower alkyl-O-lower alkyl-Q;

(5) lower alkyl-S-lower alkyl-Q;

(6) lower alkyl-O-Q;

(7) lower alkyl-S-Q;

(8) lower alkyl-O—K;

(9) lower alkyl-S—K;

(10) lower alkyl-O—V; or

(11) lower alkyl-S—V;

wherein the substituent(s) resides on the lower alkyl;

(t) cycloalkyl;

(u) aryl;

(v) arylalkyl;

(w) cycloalkylalkyl;

(x) aryloxy;

(y) arylalkoxy;

(z) arylalkylthio;

(aa) cycloalkylalkoxy;

(bb) heterocycloalkyl;

(cc) alkylsulfonyloxy;

(dd) alkylsulfonyl;

(ee) arylsulfonyl;

(ff) arylsulfonyloxy;

(gg) —C(O)R 10 ;

(hh) nitro;

(ii) amino;

(jj) aminoalkyl;

(kk) —C(O)-alkyl-heterocyclic ring;

(ll) halo;

(mm) heterocyclic ring;

(nn) —CO 2 D 1 ;

(oo) carboxyl;

(pp) amidyl; or

(qq) alkoxyalkyl;

alternatively, R 4 and R 5 together with the carbons to which they are attached are:

(a) cycloalkyl;

(b) aryl; or

(c) heterocyclic ring;

alternatively, R 4 and R 4′ or R 5 and R 5′ taken together with the carbon to which they are attached are:

(a) cycloalkyl; or

(b) heterocyclic ring;

alternatively, R 4 and R 5 , R 4′ and R 5′ , R 4 and R 5′ , or R 4′ and R 5 when substituents on adjacent carbon atoms taken together with the carbons to which they are attached are:

(a) cycloalkyl;

(b) heterocyclic ring; or

(c) aryl;

R 6 and R 7 are each independently:

(a) hydrogen;

(b) unsubstituted, mono- or di-substituted phenyl; unsubstituted, mono- or di-substituted benzyl; unsubstituted, mono- or di-substituted heteroaryl; mono- or di-substituted heteroarylmethyl, wherein said substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) —C(R 14 )(R 15 )—OD 1 ; or

(9) —C(R 14 )(R 15 )—O-lower alkyl;

(c) lower alkyl;

(d) —CH 2 OR 8 ;

(e) CN;

(f) —CH 2 CN;

(g) haloalkyl, preferably fluoroalkyl;

(h) —CON(R 8 )(R 8 );

(i) halo; or

(j) —OR 8 ;

R 8 is:

(a) hydrogen;

(b) K; or

(c) R 9 ;

alternatively, R 5 and R 5 ′, R 6 and R 7 or R 7 and R 8 together with the carbon to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms; optionally containing up to two heteroatoms selected from oxygen, S(O) o or NR i ;

R 9 is:

(a) lower alkyl;

(b) lower alkyl-CO 2 D 1 ;

(c) lower alkyl-NHD 1 ;

(d) phenyl or mono-, di- or tri-substituted phenyl, wherein the substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) lower alkyl-CO 2 D 1 ;

(6) lower alkyl-NHD 1 ;

(7) CN;

(8) CO 2 D 1 ; or

(9) haloalkyl, preferably fluoroalkyl;

(e) benzyl, mono-, di- or tri-substituted benzyl, wherein the substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) lower alkyl-CO 2 D 1 ;

(6) lower alkyl-NHD 1 ;

(7) CN;

(8) —CO 2 D 1 ; or

(9) haloalkyl, preferably CF 3 ;

(f) cycloalkyl;

(g) K; or

(h) benzoyl, mono-, di-, or trisubstituted benzoyl, wherein the substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) lower alkyl-CO 2 D 1 ;

(6) lower alkyl-NHD 1 ;

(7) CN;

(8) —CO 2 D 1 ; or

(9) haloalkyl, preferably CF 3 ;

R 10 and R 10 ′ are each independently:

(a) hydrogen; or

(b) R 11 ;

R 11 is:

(a) lower alkyl;

(b) cycloalkyl;

(c) unsubstituted, mono-, di- or tri-substituted phenyl or naphthyl, wherein the substituents are each independently:

(1) halo;

(2) alkoxy;

(3) alkylthio;

(4) CN;

(5) haloalkyl, preferably CF 3 ;

(6) lower alkyl;

(7) N 3 ;

(8) —CO 2 D 1 ;

(9) —CO 2 -lower alkyl;

(10) —C(R 12 )(R 13 )—OD 1 ;

(11) —C(R 12 )(R 13 )—O-lower alkyl;

(12) lower alkyl-CO 2 D 1 ;

(13) lower alkyl-CO 2 R 12 ;

(14) benzyloxy;

(15) —O-(lower alkyl)-CO 2 D 1 ;

(16) —O-(lower alkyl)-CO 2 R 12 ; or

(17) —O-(lower alkyl)-NR 12 R 13 ;

(d) unsubstituted, mono-, di- or tri-substituted heteroaryl, wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one heteroatom which is S, O, or N, and, optionally, 1, 2, or 3 additional N atoms; or said heteroaryl is a monocyclic ring of 6 atoms, said ring having one heteroatom which is N, and, optionally 1, 2, or 3 additional N atoms, and wherein said substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) —C(R 12 )(R 13 )—OD 1 ; or

(9) —C(R 12 )(R 13 )—O-lower alkyl;

(e) unsubstituted, mono- or di-substituted benzoheterocycle, wherein the benzoheterocycle is a 5, 6, or 7-membered ring which contains 1 or 2 heteroatoms independently selected from O, S, or N, and, optionally, a carbonyl group or a sulfonyl group, wherein said substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) —C(R 12 )(R 13 )—OD 1 ; or

(9) —C(R 12 )(R 13 )—O-lower alkyl;

(f) unsubstituted, mono- or di-substituted benzocarbocycle, wherein the carbocycle is a 5, 6, or 7-membered ring which optionally contains a carbonyl group, wherein said substituents are each independently:

(1) halo;

(2) lower alkyl;

(3) alkoxy;

(4) alkylthio;

(5) CN;

(6) haloalkyl, preferably CF 3 ;

(7) N 3 ;

(8) —C(R 12 )(R 13 )—OD 1 ; or

(9) —C(R 12 )(R 13 )—O-lower alkyl;

(g) hydrogen; or

(h) K

R 12 and R 13 are each independently:

(a) hydrogen;

(b) lower alkyl; or

(c) aryl; or

R 12 and R 13 together with the atom to which they are attached form a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms;

R 14 and R 15 are each independently:

(a) hydrogen; or

(b) lower alkyl; or

R 14 and R 15 together with the atom to which they are attached form a carbonyl, a thial, or a saturated monocyclic ring of 3, 4, 5, 6 or 7 atoms;

D 1 is:

(a) hydrogen or

(b) D;

D is:

(a) V; or

(b) K;

U is:

(a) oxygen;

(b) sulfur; or

(c) —N(R a )(R i )—;

V is:

(a) —NO;

(b) —NO 2 ; or

(c) hydrogen

K is —W aa -E b -(C(R e )(R f )) p -E c -(C(R e )(R f )) x —W d —(C(R e )(R f )) y —W i -E j -W g —(C(R e )(R f )) z —U—V;

wherein aa, b, c, d, g, i and j are each independently an integer from 0 to 3;

p, x, y and z are each independently an integer from 0 to 10;

W at each occurrence is independently:

(a) —C(O)—;

(b) —C(S)—;

(c) -T-;

(d) —(C(R e )(R f )) h —;

(e) alkyl;

(f) aryl;

(g) heterocyclic ring;

(h) arylheterocyclic ring, or

(i) —(CH 2 CH 2 O) q —;

E at each occurrence is independently:

(a) -T-;

(b) alkyl;

(c) aryl;

(d) —(C(R e )(R f )) h —;

(e) heterocyclic ring;

(f) arylheterocyclic ring; or

(g) —(CH 2 CH 2 O) q —;

h is an integer form 1 to 10;

q is an integer from 1 to 5;

R e and R f are each independently:

(a) hydrogen;

(b) alkyl;

(c) cycloalkoxy;

(d) halogen;

(e) hydroxy;

(f) hydroxyalkyl;

(g) alkoxyalkyl;

(h) arylheterocyclic ring;

(i) cycloalkylalkyl;

(j) heterocyclicalkyl;

(k) alkoxy;

(l) haloalkoxy;

(m) amino;

(n) alkylamino;

(o) dialkylamino;

(p) arylamino;

(q) diarylamino;

(r) alkylarylamino;

(s) alkoxyhaloalkyl;

(t) haloalkoxy;

(u) sulfonic acid;

(v) alkylsulfonic acid;

(w) arylsulfonic acid;

(x) arylalkoxy;

(y) alkylthio;

(z) arylthio;

(aa) cyano;

(bb) aminoalkyl;

(cc) aminoaryl;

(dd) alkoxy;

(ee) aryl;

(ff) arylalkyl;

(gg) carboxamido;

(hh) alkylcarboxamido;

(ii) arylcarboxamido;

(jj) amidyl;

(kk) carboxyl;

(ll) carbamoyl;

(mm) alkylcarboxylic acid;

(nn) arylcarboxylic acid;

(oo) alkylcarbonyl;

(pp) arylcarbonyl;

(qq) ester;

(rr) carboxylic ester;

(ss) alkylcarboxylic ester;

(tt) arylcarboxylic ester;

(uu) haloalkoxy;

(vv) sulfonamido;

(ww) alkylsulfonamido;

(xx) arylsulfonamido;

(yy) alkylsulfonyl,

(zz) alkylsulfonyloxy,

(aaa) arylsulfonyl,

(bbb) arylsulphonyloxy

(ccc) sulfonic ester;

(ddd) carbamoyl;

(eee) urea;

(fff) nitro;

(ggg) —U—V; or

(hhh) —(C(R′ e )(R′ f )) k —U—V or

R e and R f taken together are:

(a) oxo;

(b) thial;

(c) oxime; or

(d) hydrazone;

R e and R f taken together with the carbon atom to which they are attached are:

(a) heterocyclic ring;

(b) cycloalkyl group; or

(c) bridged cycloalkyl group;

R′ e and R′ f are each independently selected from R e ;

k is an integer from 1 to 3;

T at each occurrence is independently:

(a) a covalent bond,

(b) carbonyl,

(c) an oxygen,

(d) —S(O) o —; or

(e) —N(R a )(R i )—;

o is an integer from 0 to 2;

Q is:

(a) —C(O)—U-D 1 ;

(b) —CO 2 -lower alkyl;

(c) tetrazolyl-5-yl;

(d) —C(R 7 )(R 8 )(S-D 1 );

(e) —C(R 7 )(R 8 )(O-D 1 ); or

(f) —C(R 7 )(R 8 )(O-lower alkyl);

R a is:

(a) a lone pair of electron;

(b) hydrogen; or

(c) lower alkyl;

R i is:

(a) hydrogen;

(b) alkyl;

(c) aryl;

(d) alkylcarboxylic acid;

(e) arylcarboxylic acid;

(f) alkylcarboxylic ester;

(g) arylcarboxylic ester;

(h) alkylcarboxamido;

(i) arylcarboxamido;

(j) alkylsulfinyl;

(k) alkylsulfonyl;

(l) alkylsulfonyloxy,

(m) arylsulfinyl;

(n) arylsulfonyl;

(o) arylsulphonyloxy;

(p) sulfonamido;

(q) carboxamido;

(r) carboxylic ester;

(s) aminoalkyl;

(t) aminoaryl;

(u) —CH 2 —C(U—V)(R e )(R f );

(v) a bond to an adjacent atom creating a double bond to that atom; or

(w) —(N 2 O 2 —) − .M + , wherein M + is an organic or inorganic cation;

with the proviso that the compound of Formula (II) must contain at least one oxime group and/or hydrazone group.

2 . A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

3 . A method for (i) treating or reducing inflammation, pain or fever; (ii) treating a gastrointestinal disorder; (iii) improving the gastrointestinal properties of a COX-2 inhibitor; (iv) facilitating wound healing; (v) treating or reversing renal and/or respiratory toxicity; (vi) treating a disorder resulting from elevated levels of COX-2; or (vii) inhibiting platelet aggregation in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2 .

4 . The composition of claim 2 , further comprising (i) at least one therapeutic agent; (ii) at least one nitric oxide donor compound; or (iii) at least one therapeutic agent and at least one nitric oxide donor compound.

5 . The composition of claim 4 , wherein the therapeutic agent is a steroid, a nonsteroidal antiinflammatory compound, a 5-lipoxygenase (5-LO) inhibitor, a leukotriene B 4 receptor antagonist, a leukotriene A 4 hydrolase inhibitor, a 5-HT agonist, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, a H 2 antagonist, an antineoplastic agent, an antiplatelet agent, a thrombin inhibitor, a thromboxane inhibitor, a decongestant, a diuretic, a sedating or non-sedating anti-histamine, an inducible nitric oxide synthase inhibitor, an opioid, an analgesic, a Helicobacter pylori inhibitor, a proton pump inhibitor, an isoprostane inhibitor, or a mixture of two or more thereof.

6 . The composition of claim 5 , wherein the nonsteroidal antiinflammatory compound is acetaminophen, aspirin, diclofenac, ibuprofen, ketoprofen or naproxen.

7 . A method for (i) treating or reducing inflammation, pain or fever; (ii) treating a gastrointestinal disorder; (iii) improving the gastrointestinal properties of a COX-2 inhibitor; (iv) facilitating wound healing; (v) treating or reversing renal and/or respiratory toxicity; (vi) treating a disorder resulting from elevated levels of COX-2; or (vii) inhibiting platelet aggregation in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 4 .

8 . A kit comprising at least one compound of claim 1 .

9 . The kit of claim 8 , further comprising (i) at least one nitric oxide donor compound; (ii) at least one therapeutic agent; or (iii) at least one nitric oxide compound and at least one therapeutic agent.

10 . The kit of claim 9 , wherein the at least one nitric oxide donor compound; the at least one therapeutic agent; or the at least one nitric oxide donor compound and at least one therapeutic agent; are in the form of separate components in the kit.