US 5,604,253 AGranted

N-benzylindol-3-yl propanoic acid derivatives as cyclooxygenase inhibitors

AssigneeMerck Frosst Canada, Inc.

InventorsCheuk K. Lau, Cameron Black, Daniel Guay, Jacques Y. Gauthier, Yves LeBlanc, Patrick Roy, Yves Ducharme, Pierre Hamel

Life of this patent

Estimating the term…

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.

Claims16

Dependent claims

A compound of formula I ##STR16## or a pharmaceutically acceptable salt thereof, wherein:

Q is
(a) --OR or
(b) --NR.sup.9 R.sup.10 ;
R is
(a) --H or
(b) --C.sub.1-4 alkyl;
R.sup.1 is
(a) --OCH.sub.3,
(b) --OCH.sub.2 F,
(c) --OCHF.sub.2,
(d) F, Cl, Br or I, or
(e) methyl or ethyl;
R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are independently
(a) --H,
(b) --F,
(c) methyl or ethyl,
(d) --CF.sub.3, CF.sub.2 H, or CFH.sub.2,
(e) --OH, OR.sup.8, SR.sup.8, S(O)R.sup.8, or S(O).sub.2 R.sup.8,
(f) mono- or di-substituted benzyl, wherein the substituent is selected from
(1) hydrogen,
(1) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl,
(6) SR.sup.8, S(O)R.sup.8, or S(O).sub.2 R.sup.8,
(g) naphthylmethyl,
or R.sup.2 together with R.sup.3 form an oxo group;
or R.sup.4 together with R.sup.5 form an oxo group;
or R.sup.2 and R.sup.3 are joined so that together with the carbon atom to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.2 and R.sup.4 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.2 and R.sup.5 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.3 and R.sup.4 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.3 and R.sup.5 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.4 and R.sup.5 are joined so that together with the carbon atom to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
R.sup.6 is H or F;
R.sup.7 is
(a) Br, Cl or I,
(b) SMe, SEt, or SCF.sub.2 H;
R.sup.8 is methyl, ethyl or mono- or di-substituted benzyl, wherein the substituent is selected from
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
R.sup.9 and R.sup.10 are independently
(a) --H,
(b) --C.sub.1-3 alkyl,
(c) --OR,
(d) --C(O)R.sup.11,
(e) --S(O).sub.2 R.sup.12,
(f) mono-substituted C.sub.2-4 alkyl wherein the substituent is selected from
(1) hydroxy,
(2) amino,
(3) methylamino, and
(4) dimethylamino,
provided that said substituent is located on a carbon of C.sub.2-4 alkyl other than the one attached to the nitrogen of --NR.sup.9 R.sup.10,
(g) phenyl, benzyl or pyridyl optionally mono- or di-substituted, the substituents being selected from the group consisting of
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
or R.sup.9 and R.sup.10 are joined so that together with the nitrogen atom to which they are attached there is formed a saturated or unsaturated monocyclic ring of 3, 4, 5, 6, or 7 members, optionally containing one or two additional heteroatoms, said heteroatoms independently selected from N, O and S, said ring optionally containing one or two carbonyl or sulfonyl groups;
R.sup.11 is
(a) H,
(b) --C.sub.1-4 alkyl,
(c) --CF.sub.3,
(d) phenyl or benzyl optionally mono- or di-substituted, the substituents being selected from the group consisting of
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
R.sup.12 is
(a) --C.sub.1-4 alkyl,
(b) --CF.sub.3,
(c) phenyl or benzyl optionally mono- or di-substituted, the substituents being selected from the group consisting of
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
with the proviso that when Q is OR and R.sup.1 is OMe and R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are simultaneously hydrogen, R.sup.7 is other than Cl.

80 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/445,624Filed 22 May 1995
Granted: 18 Feb 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 209/22
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals: with…
C07D 403/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms

Family

No related US applications are recorded in the indexed filing history.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound of formula I ##STR16## or a pharmaceutically acceptable salt thereof, wherein:

Q is
(a) --OR or
(b) --NR.sup.9 R.sup.10 ;
R is
(a) --H or
(b) --C.sub.1-4 alkyl;
R.sup.1 is
(a) --OCH.sub.3,
(b) --OCH.sub.2 F,
(c) --OCHF.sub.2,
(d) F, Cl, Br or I, or
(e) methyl or ethyl;
R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are independently
(a) --H,
(b) --F,
(c) methyl or ethyl,
(d) --CF.sub.3, CF.sub.2 H, or CFH.sub.2,
(e) --OH, OR.sup.8, SR.sup.8, S(O)R.sup.8, or S(O).sub.2 R.sup.8,
(f) mono- or di-substituted benzyl, wherein the substituent is selected from
(1) hydrogen,
(1) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl,
(6) SR.sup.8, S(O)R.sup.8, or S(O).sub.2 R.sup.8,
(g) naphthylmethyl,
or R.sup.2 together with R.sup.3 form an oxo group;
or R.sup.4 together with R.sup.5 form an oxo group;
or R.sup.2 and R.sup.3 are joined so that together with the carbon atom to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.2 and R.sup.4 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.2 and R.sup.5 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.3 and R.sup.4 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.3 and R.sup.5 are joined so that together with the carbon atoms to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
or R.sup.4 and R.sup.5 are joined so that together with the carbon atom to which they are attached there is formed a saturated monocyclic hydrocarbon ring of 3, 4, 5, 6 or 7 members;
R.sup.6 is H or F;
R.sup.7 is
(a) Br, Cl or I,
(b) SMe, SEt, or SCF.sub.2 H;
R.sup.8 is methyl, ethyl or mono- or di-substituted benzyl, wherein the substituent is selected from
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
R.sup.9 and R.sup.10 are independently
(a) --H,
(b) --C.sub.1-3 alkyl,
(c) --OR,
(d) --C(O)R.sup.11,
(e) --S(O).sub.2 R.sup.12,
(f) mono-substituted C.sub.2-4 alkyl wherein the substituent is selected from
(1) hydroxy,
(2) amino,
(3) methylamino, and
(4) dimethylamino,
provided that said substituent is located on a carbon of C.sub.2-4 alkyl other than the one attached to the nitrogen of --NR.sup.9 R.sup.10,
(g) phenyl, benzyl or pyridyl optionally mono- or di-substituted, the substituents being selected from the group consisting of
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
or R.sup.9 and R.sup.10 are joined so that together with the nitrogen atom to which they are attached there is formed a saturated or unsaturated monocyclic ring of 3, 4, 5, 6, or 7 members, optionally containing one or two additional heteroatoms, said heteroatoms independently selected from N, O and S, said ring optionally containing one or two carbonyl or sulfonyl groups;
R.sup.11 is
(a) H,
(b) --C.sub.1-4 alkyl,
(c) --CF.sub.3,
(d) phenyl or benzyl optionally mono- or di-substituted, the substituents being selected from the group consisting of
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
R.sup.12 is
(a) --C.sub.1-4 alkyl,
(b) --CF.sub.3,
(c) phenyl or benzyl optionally mono- or di-substituted, the substituents being selected from the group consisting of
(1) hydrogen,
(2) CF.sub.3,
(3) CN,
(4) F, Cl, Br or I,
(5) C.sub.1-6 alkyl;
with the proviso that when Q is OR and R.sup.1 is OMe and R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are simultaneously hydrogen, R.sup.7 is other than Cl.

80 more elements

Facts

Application

08/445,624Filed 22 May 1995

Granted

18 Feb 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification5 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 209/22
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals: with…
C07D 403/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms