2-phenyl-4-quinolinecarboxylic acids and pharmaceutical compositions thereof

Claim 2

A compound having the formula: ##STR37## wherein ##STR38## R 1 is cyclohexyl, ##STR39## when R is ##STR40## R 1 can be in addition alkyl of 3-4 carbon atoms; R 2 is ##STR41## R 3 is H, alkoxy of 1-3 carbon atoms, or alkyl of 1-2 carbon atoms; R 4 is CO 2 H or CO 2 R 11 ; R 5 , R 6 , R 7 and R 8 are independently H, F, Cl, Br, I, CH 3 , CF 3 , SCH 3 or CH 2 CH 3 , at least two of R 5 , R 6 , R 7 , and R 8 being H; R 9 and R 9A are independently H or alkyl of 1 to 3 carbon atoms; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; W, Y and Z are independently H, F, Cl, Br, alkyl of 1-5 carbon atoms, NO 2 , OH, CF 3 or OCH 3 ; m is 0 or 1; or a pharmaceutically suitable salt thereof; with the following provisos: (1) when R 4 is CO 2 H, R 1 is phenyl or phenoxy, and R 5 , R 7 and R 8 are H, R 6 cannot be Br; (2) R 5 , R 6 and R 7 cannot all be H; (3) when R 4 is CO 2 CH 2 CH 2 N(CH 3 ) 2 , R 6 is CH 2 CH 3 , or R 7 is Cl, R 1 cannot be cyclohexyl; (4) when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F, but R 6 and R 8 cannot both be Cl; and (5) when R 6 is CH 3 , R 7 cannot be Cl.

Claim 3

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one comound of claim 1.

Claim 4

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound having the formula: ##STR42## wherein ##STR43## R 1 is CH 3 CH 2 (CH 3 )CH, alkyl of 5-12 carbon atoms, cyclohexyl, ##STR44## when R is ##STR45## R 1 can be in addition alkyl of 3-4 carbon atoms; R 2 is ##STR46## R 3 is H, alkoxy of 1-3 carbon atoms, or alkyl of 1-2 carbon atoms; R 4 is CO 2 H or CO 2 R 11 ; R 5 , R 6 , R 7 and R 8 are independently H, F, Cl, Br, I, CH 3 , CF 3 , SCH 3 or CH 2 CH 3 , at least two of R 5 , R 6 , R 7 , and R 8 being H; R 9 and R 9A are independently H or alkyl of 1 to 3 carbon atoms; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; W, Y and Z are independently H, F, Cl, Br, alkyl of 1-5 carbon atoms, NO 2 , OH, CF 3 or OCH 3 ; m is 0 or 1; or a pharmaceutically suitable salt thereof; with the following provisos: (1) R 5 , R 6 and R 7 cannot all be H; (2) when R 4 is CO 2 CH 2 CH 2 N(CH 3 ) 2 , R 6 is CH 2 CH 3 , or R 7 is Cl, R 1 cannot be cyclohexyl; (3) when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F, but R 6 and R 8 cannot both be Cl; and (4) when R 6 is CH 3 , then R 7 cannot be Cl.

Claim 5

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound having the formula: ##STR42## wherein ##STR43## R 1 is CH 3 CH 2 (CH 3 )CH, alkyl of 5-12 carbon atoms, cyclohexyl, ##STR44## when R is ##STR45## R 1 can be in addition alkyl of 3-4 carbon atoms; R 2 is ##STR46## R 3 is H, alkoxy of 1-3 carbon atoms, or alkyl of 1-2 carbon atoms; R 4 is CO 2 H or CO 2 R 11 ; R 5 , R 6 , R 7 and R 8 are independently H, F, Cl, Br, I, CH 3 , CF 3 , SCH 3 or CH 2 CH 3 , at least two of R 5 , R 6 , R 7 , and R 8 being H; R 9 and R 9A are independently H or alkyl of 1 to 3 carbon atoms; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; W, Y and Z are independently H, F, Cl, Br, alkyl of 1-5 carbon atoms, NO 2 , OH, CF 3 or OCH 3 ; m is 0 or 1; or a pharmaceutically suitable salt thereof; with the following provisos: (1) R 5 , R 6 and R 7 cannot all be H; (2) when R 4 is CO 2 CH 2 CH 2 N(CH 3 ) 2 , R 6 is CH 2 CH 3 , or R 7 is Cl, R 1 cannot be cyclohexyl; (3) when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F, but R 6 and R 8 cannot both be Cl; and (4) when R 6 is CH 3 , then R 7 cannot be Cl.

Claim 6

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound having the formula: ##STR47## wherein R 1 is cyclohexyl; phenyl; phenyl substituted with one halogen; alkyl of 1-5 carbon atoms or CF 3 ; phenoxy; or phenoxy substituted with one halogen or alkyl of 1-5 carbon atoms; R 3 is H or alkyl of 1-2 carbon atoms; R 4 is CO 2 H, a sodium or potassium salt theeof, or CO 2 R 11 ; R 5 and R 6 are independently H, halogen, CH 3 or CF 3 ; R 7 and R 8 are independently H or halogen; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; and R 9 and R 9A are independently alkyl of 1 to 3 carbon atoms, or a pharmaceutically suitable salt thereof; provided that R 5 , R 6 and R 7 cannot all be H and that when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F, but R 6 and R 8 cannot both be Cl, and when R 6 is CH 3 , then R 7 cannot be Cl.

Claim 7

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound having the formula: ##STR47## wherein R 1 is cyclohexyl; phenyl; phenyl substituted with one halogen; alkyl of 1-5 carbon atoms or CF 3 ; phenoxy; or phenoxy substituted with one halogen or alkyl of 1-5 carbon atoms; R 3 is H or alkyl of 1-2 carbon atoms; R 4 is CO 2 H, a sodium or potassium salt theeof, or CO 2 R 11 ; R 5 and R 6 are independently H, halogen, CH 3 or CF 3 ; R 7 and R 8 are independently H or halogen; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; and R 9 and R 9A are independently alkyl of 1 to 3 carbon atoms, or a pharmaceutically suitable salt thereof; provided that R 5 , R 6 and R 7 cannot all be H and that when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F, but R 6 and R 8 cannot both be Cl, and when R 6 is CH 3 , then R 7 cannot be Cl.

Claim 8

A compound having the formula: ##STR48## wherein R 1 is cyclohexyl, ##STR49## R 3 is H or alkyl of 1-2 carbon atoms; R 4 is CO 2 H, a sodium or potassium salt thereof, or CO 2 R 11 ; R 5 and R 6 are independently H, halogen or CF 3 provided that both R 5 and R 6 are not hydrogen; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; R 9 and R 9A are independently alkyl of 1 to 3 carbon atoms; and W and Z are independently H, halogen, alkyl of 1-5 carbon atoms or CF 3 ; provided that when R 1 is phenyl or phenoxy, and R 5 is H, then R 6 cannot be Br; and that when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F.

Claim 9

A compound having the formula: ##STR48## wherein R 1 is cyclohexyl, ##STR49## R 3 is H or alkyl of 1-2 carbon atoms; R 4 is CO 2 H, a sodium or potassium salt thereof, or CO 2 R 11 ; R 5 and R 6 are independently H, halogen or CF 3 provided that both R 5 and R 6 are not hydrogen; R 11 is (CH 2 ) 2-4 NR 9 R 9A ; R 9 and R 9A are independently alkyl of 1 to 3 carbon atoms; and W and Z are independently H, halogen, alkyl of 1-5 carbon atoms or CF 3 ; provided that when R 1 is phenyl or phenoxy, and R 5 is H, then R 6 cannot be Br; and that when R 1 is cyclohexyl and R 3 is H, R 6 must be Cl or F.

Claim 10

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 5.

Claim 11

A compound of claim 5 wherein: R 1 is phenyl, phenyl substituted with at least one halogen, phenoxy, or phenoxy substituted with at least one halogen; R 3 is methyl; R 5 is H or Cl; and R 6 H, F or Cl.

Claim 12

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 7.

Claim 13

The compound of claim 5 which is 2-(1,1'-biphenyl-4-yl)-6-fluoro-3-methyl-4-quinolinecarboxylic acid, sodium or potassium salt.

Claim 14

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 9.

Claim 15

The compound of claim 5 which is 6-fluoro-3-methyl-2-(4-phenoxyphenyl)-4-quinolinecarboxylic acid, sodium or potassium salt.

Claim 16

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 11.

Claim 17

The compound of claim 5 which is 2-(4'-bromo-1,1'-biphenyl-4-yl)-6-fluoro-3-methyl-4-quinolinecarboxylic acid, sodium or potassium salt.

Claim 18

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 13.

Claim 19

The compound of claim 5 which is 2-(2'-fluoro-1,1'-biphenyl-4-yl)-6-fluoro-3-methyl-4-quinolinecarboxylic acid, sodium or potassium salt.

Claim 20

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 15.

Claim 21

The compound of claim 5 which is 2-(1,1'-biphenyl-4-yl)-5-chloro-6-fluoro-3-methyl-4-quinolinecarboxylic acid, sodium or potassium salt.

Claim 22

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 17.

Claim 23

The compound of claim 5 which is 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-[(2-dimethylamino)ethyl]ester-4-quinolinecarboxylic acid]hydrochloride.

Claim 24

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and the compound of claim 19.

Claim 25

The compound of claim 5 which is 2-(1,1'-biphenyl-4-yl)-5-chloro-3-methyl-4-quinolinecarboxylic acid, sodium or potassium salt.

Claim 26

A pharmaceutical composition consisting essentially of a suitable pharmaceutical carrier and at least one compound of claim 21.