Diarylstyrylquinoline diacids

Claim 2

A compound of the formula: wherein: R 1 is H, halogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, -CF 3 , -SR 2 , -S(O)R 2 . -S(0) 2 R 2 , -NR 3 R 3 , -OR 3 , -COOR 3 , -(C=O)R 3 , -C(OH)R 3 R 3 , -CN, -N0 2 , -N 3 , substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted 2-phenethyl, or substituted or unsubstituted pyridyl; R 2 is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, -CF 3 , substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted 2-phenethyl; R 3 is H or R 2 ; R 4 is H, halogen, -N0 2 , -CN, -OR 3 , -SR 3 , NR 3 R 3 , or C 1 -C 8 alkyl; CR 3 R 4 may be the radical of a naturally occurring amino acid; R 5 is H, halogen, -N0 2 , -N 3 , -CN, -SR 2 , -NR 3 R 3 , -OR 3 , C 1 -C 8 alkyl, -(C=0)R 3 , or -S(O) 2 R 2 ; R 6 is -(CH 2 ) s -C(R 7 R 7 )-(CH 2 ) 5 -R 8 or -CH 2 CONR 12 R 12 ; R 7 is H or C 1 -C 4 alkyl; R 8 is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N, S or O and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or B) the radical W-R 9 ; R 9 contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring; R 10 is -SR 11 , -OR 12 , or -NR 12 R 12 ; R" is C 1 -C 6 alkyl, -(C=O)R 14 , substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl; R 12 is H, R 11 , adamantyl, naphthyl, halogen-substituted C 1 -C 6 -alkyl, C 1 -C 6 alkylene-OR 3 , or two R 12 groups joined to the same N may form a ring of 5 or 6 members containing up to two heteroatoms chosen from O, S or N; R 13 is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, -CF 3 , or unsubstituted phenyl, benzyl, or 2-phenethyl; R 14 is H or R' 3 ; R 15 is R 3 or halogen; R' 6 is H, C 1 -C 4 alkyl, or OH; R 17 is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl; R 18 is C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, -CF 3 , or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl; R 19 is C 4 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, -CF 3 , substituted phenyl, or unsubstituted phenyl, benzyl, or 2-phenethyl; R 20 is H or R 17 ; m and m' are independently 0-8; n and n are independently 0 or 1 but not both 0; p and p are independently 0-8; m + n + p is 1-10 when X 2 is O, S, S(O), or S(0) 2 ; m + n + p is 0-10 when X 2 is CR 3 R 16 ; m' + n' + p' is 1-10 when X 3 is 0, S, S(O), or S(0) 2 ; m' + n' + p' is 0-10 when X 3 is CR 3 R' 6 ; r is 0 or 1 when Z' is HET (- R 3, - R s ); r is 1 when Z' is -CONR 3 or when n=0; r' is 0 or 1 when Z 2 is HET(-R3,- R 5); r is 1 when Z 2 is CONR 3 or when n'=0; s is 0-3; Q 1 and Q 2 are independently -COOR 3 , tetrazole, methyltetrazole, -COOR 6 , -CONHS(O) 2 R 13 , -CN, - CONR 12 R 12 , -CHO, -CH 2 0H, -COCH 2 0H, -NR 7 S(O) 2 R 13 ; -C(O)R 19 , -NR 20 C(O)OR 17 , -NR 12 G(O)NR 12 R 12 , -NR 7 C(O)R 18 , -OC(O)NR 12 R 12, -S(O) 2 R 18 , -S(O)R 18 , -S(O) 2 NR 12 R 12 , -N0 2 , S-substituted phenyl. or if Q 1 or Q 2 is COOH and R 4 is -OH, -SH, or -NHR 3 then Q 1 or Q 2 and R 4 and the carbons through which they are attached may form a heterocyclic ring by loss of water; W is O, S, or NR 3 ; X 1 is O, S, -S(O)-, -S(0) 2 -, -NR 3 , or -CR 3 R 3- ; X 2 and X 3 are independently O, S, S(O), S(O) 2 , or CR 3 R 16 ; Y is -CR 3 = CR 3-, -C≡C-, -CR 3 R 3 -X 1 -, -X 1 -CR 3 R 3 -, -CR 3 R 3 -X 1 -CR 3 R 3 -, O, S, or N R 3; Z 1 and Z 2 are independently -CONR 3- or -HET(-R 3- R s )-, provided that at least one of them is -HET(-R 3 ,-R s )-HET is and the pharmaceutically acceptable salts thereof.

Claim 3

A compound of Claim 1 wherein the substituents are as follows:

Claim 4

A compound of Claim 2 which is: 2-(3-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-3-(2-carboxyethylthio)propyl)benzoic acid, disodium salt; 2-(3-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-3-(2-(dimethylcarbamoyl)ethylthio)propyl)benzoic acid, sodium salt; 3-(3-(2-(7-chloroquinolin-2-yl)ethyl)phenyl)-(2-(dimethylcarbamoyl)ethylthio)methyl)benzoic acid, sodium salt; 5-((3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)(2-(dimethylcarbamoyl)ethylthio)methyl)thiophene-2-carboxylic acid; 3-((3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)(2-(dimethylcarbamoyl)ethylthio)methyl)benzoic acid; 4-((3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)(2-(dimethylcarbamoyl)ethylthio)methyl)benzoic acid; 3-((2-carboxyethylthio)(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)methyl)benzoic acid; 6-(3-carboxyphenylthio)-6-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-3-methylhexanoic acid; 3-((3-((7-chloroquinolin-2-ylmethyl)oxy)phenyl)(2-(dimethylcarbamoyl)ethylthio)methyl)benzoic acid, sodium salt; 3-((3-carboxyphenylthio)(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)methyl)benzoic acid; 3-((3-((7-chloroquinolin-2-ylmethyl)oxy)phenyl)(2-(t-butylcarbamoyl)ethylthio)methyl)benzoic acid, sodium salt; 5-((3-((7-chloro-2-quinolinyl)methoxy)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)-3-pyridinecarboxylic acid, sodium salt: 3,3'-(((3-((7-Chloro-2-quinolinyl)methoxy)phenyl)methylene)bis(thio))bis(benzoic acid), disodium salt; 3-(((4-Carboxyphenyl)thio)(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)methyl)benzoic acid, disodium salt; 3-((3-(2-(7-Chloro-2-quinolinyl)ethenyl)phenyl)((4-(dimethylaminocarbonyl)phenyl)thio)methyl)benzoic c acid, sodium salt; 3-(2-((2-Carboxyethyl)thio)-2-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)ethyl)benzoic acid; 3-(1-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-1-((2-carboxy-4-pyridinyl)thio)methyl)benzoic acid; 3-(1-((2-carboxyphenyl)thio)-1-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)methyl)benzoic acid, disodium salt; 2-(3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-((2-carboxyethyl)thio)propyl)benzoic acid; 2-(3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-((3-dimethylamino-3-oxopropyl)thio)propyl)benzoic acid, sodium salt; 2,2-(((3-((7-chloro-2-quinolinyl)methoxy)phenyl)methylene)bis(thio))bis(benzoic acid), disodium salt; 2-chloro-5-((3-((7-chloro-2-quinolinyl)methoxy)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)benzoic acid, sodium salt; 2,2'-(((3-((7-chloro-2-quinolinyl)methoxy)phenyl)methylene)bis(thiomethyl))bis(benzoic acid), disodium salt; 2-((((3-((7-chloro-2-quinolinyl)methoxy)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)thio)methyl)benzoic acid; 3-((3-(2-(7-Chloro-2-quinolinyl)ethenyl)phenyl)((4-(dimethylamino)-4-oxopropyl)thio)methyl)benzoic acid; 2-(3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-((3-((2-methyl-2-propyl)amino)-3-oxopropyl)thio)propyl)-benzoic acid, sodium salt; 2-(3-(3-(2-(7-chloro-2-quinolinyl)ethyl)phenyl)-3-((3-((2-methyl-2-propyl)amino)-3-oxopropyl)thio)propyl)-benzoic acid; 3-(3-(3-(2-(7-chloro-2-quinolinyl)ethyl)phenyl)-3-((3-dimethylamino)-3-oxopropyl)thio)propyl)benzoic acid; 2-((3-((7-chloro-2-quinolinyl)methoxy)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)benzoic acid; 2-(3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-((3-oxo-3-(1-(tricyclo[3.3.1.1 3.7 ]decyl)amino)propyl)thio)-propyl)benzoic acid, sodium salt; N,N-dimethyl 3-((1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(1 H-tetrazol-5-yl)phenyl)propyl)thio)-propanamide, sodium salt; N,N-dimethyl 3-((1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-(2-((1 H-tetrazol-5-yl)methyl)phenyl)propyl)-thio)propanamide, sodium salt; 2-(3-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-((3-dimethylamino-3-oxopropyl)thio)propyl)benzeneacetic acid, sodium salt; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(dimethylaminocarbonyl)phenyl)propyl)thio)propanoic acid, sodium salt; N,N-dimethyl 3-((1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-1-(3-((1 H-tetrazol-5-yl)methyl)phenyl)methyl)-thio)propanamide, sodium salt; 3-(((3-Carboxyphenyl)thio)(3-((7-chloro-2-quinolinyl)methoxy)phenyl)methyl)benzoic acid, disodium salt; 3-(((3-((7-Chloro-2-quinolinyl)methoxy)phenyl) (3-(2-dimethylamino-2-oxoethyl)phenyl)methyl)thio)propanoic acid, sodium salt; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(4-chloro-2-(dimethylaminocarbonyl)phenyl)propyl)thio)-propanoic acid; N,N-Dimethyl 2-(3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-((2-(1 H-tetrazol-5-yl)ethyl)thio)propyl)-benzamide, sodium salt; N,N-Dimethyl 2-(3-(3-(2-(7-chloro-2-quinolinyl)ethyl)phenyl)-3-((2-(1 H-tetrazol-5-yl)propyl)thio)propyl)-benzamide, sodium salt; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(dimethylaminocarbonyl)phenyl)propyl)thio)-2-ethylpropanoic acid, sodium salt; 3-((1-(3-(2-(7-Chloro-2-quinolinyl)ethyl)phenyl)-3-(2-(1 H-tetrazol-5-yl)phenyl)propyl)thio)-2-ethylpropanoic, disodium salt; 3-((1-(3-(2-(7-Chloro-2-quinolinyl)ethyl)phenyl )-3-(2-((4-methylphenylsulfonylaminocarbonyl)phenyl)propyl)-thio)-2-ethylpropanoic acid, monosodium salt; 3-((1-(3-(2-(7-Chloro-2-quinolinyl)ethyl)phenyl)-3-(2-(N-methyl-1 H-tetrazol-5-yl)phenyl)propyl)thio)-2-ethylpropanoic acid, disodium salt; 2-(3-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-((2-ethyl-3-(dimethylamino)-3-oxo-propyl)thio)propyl)-benzoic acid, sodium salt; 2-(3-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-((3-amino-2-ethyl-3-oxopropyl)thio)propyl) benzoic acid, sodium salt; 3-((1-(3-(2-(7-Chloro-2-quinolinyl)ethyl)phenyl)-3-(2-((ethoxycarbonyl)amino)phenyl)propyl)thio)-2-ethylpropanoic acid, sodium salt; 3-(((3-((7-Chloro-2-quinolinyl)methoxy)phenyl)(((2-(dimethylaminocarbonyl)phenyl)methyl)thio)methyl)thio)-propanoic acid, sodium salt; 3-((3-(2-(Aminocarbonyl)phenyl)-1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)thio)-2-methoxypropanoic acid, sodium salt; 3-((1-(3-(2-(7-Chloro-2-quinolinyl)ethyl)phenyl)-3-(2-cyanophenyl)propyl)thio)-2-ethylpropanoic acid. sodium salt; 3-((3-(4-Chloro-2-(methylaminocarbonyl)phenyl)-1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)thio)-propanoic acid; 5-Chloro-2-(3-((2-carboxyethyl)thio)-3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)benzoic acid; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(1-(hydroxyimino)ethyl)phenyl)propyl)thio)-2-methylpropanoic acid, sodium salt; (+)-3-((1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-(4-chloro-2-dimethylaminocarbonyl)phenyl)propyl)-thio)propanoic acid, sodium salt; (-)3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(4-chloro-2-(dimethylaminocarbonyl)phenyl)propyl)thio)-propanoic acid, sodium salt; 3-((3-(4-Chloro-2-((ethoxycarbonyl)amino)phenyl)-1-(3-((7-chloro-2-quinolinylmethoxy)phenyl)propyl)thio)-propanoic acid, sodium salt; 3-((3-(2-Chloro-6-(dimethylaminacarbonyl)phenyl)-1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)thio)-propanoic acid; 3-((3-(4-Chloro-2-(dimethylaminocarbonyl)phenyl)-1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)-sulfinyl)propanoic acid, sodium salt; 3-((3-(3-Chloro-2-(dimethylaminocarbonyl)phenyl)-1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)thio)-pro-panoic acid, sodium salt; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(1 H-tetrazol-5-yl)phenyl)propyl)thio)-2-methylpropanoic acid, disodium salt; 3-((1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(aminocarbonyl)phenyl)propyl)thio)-2-methylpropanoic acid, sodium salt; (+) 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(dimethylaminocarbonyl)phenyl)propyl)thio)-propanoic acid, sodium salt; (-) 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(dimethylaminocarbonyl)phenyl)propyl)thio)-propanoic acid, sodium salt; 5-Bromo-2-(3-((2-carboxyethyl)thio)-3-(3-((7-chloro-2-quinolinyl)methoxy)phenyipropyl)benzoic acid, disodium salt; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(4-chloro-2-(dimethylaminocarbonyl)phenyl)propyl)thio)-butanoic acid, sodium salt; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(5-(dimethylaminocarbonyl)-2-furanyl)propyl)thio)-propanoic acid, sodium salt; 3-((3-(2-(Acetylamino)-4-chforophenyl)-1-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)thio)propanoic acid; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyp-3-(4-chloro-2-(((methylsulfonyl)amino)carbonyl)phenyl)-propyl)thio)propanoic acid, disodium salt; 5-Chloro-2-(3-((2-carboxybutyl)thio)-3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)benzoic acid, disodium salt; 5-Chloro-2-(3-((2-carboxypropyl)thio)-3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)benzoic acid, disodium salt; 5-Chloro-2-(3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)-3-(2-carboxy-2-methoxyethyl)thio)propyl)benzaic acid, disodium salt; 2-(3-((2-Carboxyethyl)thio)-3-(3-((7-chloro-2-quinolinyl)methoxy)phenyl)propyl)-5-phenylbenzoic acid; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-(dimethylaminocarbonyl)-3-pyridinyl)propyl)thio)-propanoic acid, sodium salt; 3-((3-(4-Chloro-2-(dimethylaminocarbonyl)phenyl)-1-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)propyl)thio)-propanoic acid; 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(4-chloro-2-(1 H-tetrazol-5-yl)phenyl)propyl)thio)propanoic acid, disodium salt; or 3-((1-(3-((7-Chloro-2-quinolinyl)methoxy)phenyl)-3-(2-cyanophenyl)propyl)thio)-2-methylpropanoic acid, sodium salt.

Claim 5

A compound of Claim 1 wherein: R 1 is H, halogen, C 1 -C 8 alkyl, -CF 3 , -SR 2 , -S(O)R 2 , -S(O) 2 R 2 , -OR 3 , or -CN; R 2 is C 1 -C 8 alkyl or -CFa; R 4 is H, -OR 3 , -SR 3 , NR 3 R 3 , or C 1 -C 8 alkyl; CR 3 R 4 may be the radical of a naturally occurring amino acid; R 5 is H, halogen, -CN, -SR 2 , -OR 3 , C 1 -C 8 alkyl, or -(C = O ) R 3; R 13 is C 1 -C 8 alkyl, -CF 3 , or unsubstituted phenyl, benzyl, or 2-phenethyl; m and m are independently 0-4; p and p are independently 0-4; m + n + p is 1-10 when X 2 is O or S; m' + n + p is 1-10 when X 3 is 0 or S; Q 1 and Q 2 are independently -COOR 3 , tetrazole, -COOR 6 , -CONHS(O) 2 R 13 , -CONR 12 R 12 , -NHS(O) 2 R 13 ; or if Q 1 or Q 2 is COOH and R 4 is -OH, -SH, or -NHR 3 then Q 1 or Q 2 and R 4 and the carbons through which they are attached may form a heterocyclic ring by loss of water; W is O, S, or NH; X 1 is O, S, -NR 3 , or -CR3R3-; X 2 and X 3 are independently O, S, or CR 3 R 16 ; Y is -CR 3 = CR3-, -C=C-, -CR 3 R 3- X 1 -, or -X'-CR 3 R 3- ; and the pharmaceutically acceptable salts thereof.

Claim 6

A compound of Claim 1 wherein: R 1 is H, halogen, C 1 -C 8 alkyl, -CF 3 , -SR 2 , -S(O)R 2 , -S(O) 2 R 2 , -OR 3 , or -CN; R 2 is C 1 -C 8 alkyl or -CF 3 ; R 4 is H, -OR 3 , -SR 3 , NR 3 R 3 , or C 1 -C 8 alkyl; CR 3 R 4 is not the radical of a naturally occurring amino acid; R 5 is H, halogen, -CN, -SR 2 , -OR 3 , C 1 -C 8 alkyl, or -(C=O)R 3 ; R 13 is C 1 -C 8 alkyl, -CF 3 , or unsubstituted phenyl, benzyl, or 2-phenethyl; m and m are independently 0-4; p and p are independently 0-4; m + n + p is 1-10 when X 2 is O or S; m' + n + p is 1-10 when R 3 is 0 or S; Q 1 and Q 2 are independently -COOR 3 , tetrazole, or -CONR 12 R 12 ; W is 0, S, or NH; X 1 is O, S, -NR 3 , or -CR3 R 3-; X 2 and X 3 are independently 0, S, or CR 3 R 16 ; Y is -CH=CH-; Z 1 and Z 2 are HET(- R 3- R 5) ; and the pharmaceutically acceptable salts thereof.

Claim 7

A compound of the formula: wherein: R4 is H or C 1 -C 8 alkyl; CR 3 R 4 is not the radical of a naturally occurring amino acid; m is 1-4; m is 0-4; p' is 0-4; r is 0 or 1; Q 1 and Q 2 are independently -COOR 3 , tetrazole, -CONHS(O) 2 R 13 , or -CONR 12 R 12 ; X 3 is S or CR 3 R 16 ; Y is -CH=CH- or -CH 2 0-; and the rest of the definitions are as in Claim 4.

Claim 8

A compound of Claim 1 of the formula Ib wherein: R 1 is halogen, R5 is H, halogen, -C N, -SR 2 , -S(O) 2 R 2 , or -OR 2 ; R 7 is H or C 1 -C 4 alkyl; R 21 is R 7 or -O-C 1 -C 4 alkyl; r is 0 or 1; m' is 0-2; p' is 0 or 1; Q 2 is as defined for Formula I; X 3 is S or CH 2 ; and Y is -CH2CH2-, -CH = CH- or -CH 2 0-.

Claim 9

A pharmaceutical composition comprising a therapeutically effective amount of a compound of Claim 1 and a pharmaceutically acceptable carrier.

Claim 10

The pharmaceutical composition of Claim 8 additionally comprising an effective amount of a second active ingredient selected from the group consisting of non-steroidal anti-inflammatory drugs; peripheral analgesic agents; cyclooxygenase inhibitors; leukotriene antagonists: leukotriene bisynthesis inhibitors; H 2 - receptor antagonists; antihistaminic agents; prostaglandin antagonists; thromboxane antagonists; thromboxane synthetase inhibitors; and ACE antagonists.

Claim 11

A pharmaceutical composition according to Claim 7, wherein the second active ingredient is a non-steroidal anti-inflammatory drug.

Claim 12

A pharmaceutical composition of Claim 10, wherein the weight ratio of said compound of Claim 1 to said second active ingredient ranges from about 1000:1 to 1:1000.

Claim 13

The use of a compound according to Claim 1 for the manufacture of a medicament useful for preventing the synthesis, the action, or the release of SRS-A or leukotrienes in a mammal.

Claim 14

The use according to Claim 12 wherein the mammal is man.

Claim 15

The use of a compound according to Claim 1 for the manufacture of a medicament useful for inducing cytoprotection in a mammal.

Claim 16

The use of a compound according to Claim 1 for the manufacture of a medicament useful for treating inflammatory diseases of the eye in a mammal.

Claim 17

The use according to Claim 15 wherein the mammal is man.

Claim 18

A compound of Claim 1 wherein the substituents are as follows: