Lipoxygenase inhibitors

Claim 1

A pharmaceutical composition, useful for inhibiting the biosynthesis of mammalian leukotrienes comprising a pharmaceutically acceptable carrier and a compound having the Formula I or a compound that is a pharmaceutically acceptable salt thereof:- wherein: Z is a bond, CR 14 = CR 15 or CHR 14 -CHR 15 ; X is 0, S, SO, or SO 2 ; R 2 is H, OH, C 1 to C 20 alkoxy, including straight chain or branched chain, cycloalkyl, bicycloalkyl, tricycloalkyl or tetracycloalkyl; Ar 1 -C 1 to C 3 alkoxy; NR 8 Ar l , wherein R 8 and Ar 1 can optionally be joined to form a heterocyclic ring having 5 to 8 ring atoms; -NR 8 Het; -N(R 8 )C H 2 Ar l ; -N(R 13 )-N(R 13 ) 2 wherein each R 13 is independently hydrogen, R 8 , R 9 , Ar 1 or Het; -NH-CH=C( Ar l ) 2 ; -O(CH 2 ) n NR 8 R 9 wherein n is 2 to 4; -Z-Ar 1 ; -lower acyloxy-lower alkoxy; -CH 2 OH; -(CH 2 ) n Ar l wherein n is 0 to 3; (CH 2 ) n COOR 6 wherein n is 0 to 6; C 1 to C 20 alkyl; Ar l ; Het ; (CH 2 ) n NR 8 R 9 wherein n is 1 to 3; or -Het; and R 1 , R 3 , R 4 , T and V are each independently selected from: (1) hydrogen; (2) alkyl having 1 to 6 carbon atoms; (3) alkenyl having 2 to 6 carbon atoms; (4) - (CH 2 ) n M wherein n is 0 to 6 except when X is S and M is OR 5 , in which case n is 1 to 6 and M is (a) -OR 5 ; (b) halogen; (c) -CF 3 ; (d) -SR 5 ; (e) Ar 1 ; (f) -COOR 6 ; wherein R 12 is H, C 1 to C 6 alkyl, or Ar i ; (h) tetrazole; (m) -NR 8 R 9 ; (n) -NHSO 2 R 10 wherein R 10 is OH, C 1 to C 6 alkyl, C F 3 , C 1 to C 6 -alkoxy, or Ar l ; ( p ) -SOR 5 ; ( q ) -CONR 8 R 9 ; (r) -SO 2 NR 8 R 9 ; (s) -SO 2 R 5 ; (t) -NO 2 ; or (u) -CN; or any two of R 3 , R 4 , T and V may be joined to form a saturated ring having 5 to 6 ring atoms, said ring atoms comprising 0, 1 or 2 atoms selected from oxygen and sulfur, the remaining ring atoms being carbon; each R 5 is independently H, C 1 to C 6 alkyl, benzyl, Ar 1 , perfluoro-C 1 to C 4 alkyl, CH 2 -R 11 wherein R 11 is C 1 to C 5 alkyldimethylamino, hydroxy-C 2 to C 5 alkyl, CH 2 COOR 6 , or CH 2 CO-R 7 ; each R 6 is independently H or C 1 to C 6 alkyl; each R 7 is independently C 1 to C 6 alkyl, benzyl, Ar l , NR 8 R 9 , NHAr 1 , or O-C 1 to C 4 to alkyl; each R 8 and each R 9 is independently H or C 1 to C 4 alkyl, or R 8 and R 9 may be joined through the N to which they are attached to form a heterocycloalkyl ring having 5 to 8 ring atoms; each Het is independently an aromatic heterocyclic ring having 5 or 6 ring atoms, one or more of which are selected from N, O and S; each Ar 1 is independently 1- or 2- naphthyl, phenyl or mono- or disubstituted phenyl, wherein the substituents on the phenyl are independently selected from C 1 to C 3 alkyl, I, Br, Cl, F, COOR 6 , (CH 2 ) n -NR 8 R 9 wherein n is 0 to 2, methylenedioxy, C 1 to C 3 alkoxy, OH, CN, N0 2 , CF 3 , C 1 to C 4 acyl, NR 8 R 9 , S-C l to C 6 alkyl, SO-C 1 to C 6 alkyl, and SO 2 -C 1 to C 6 alkyl; and R 14 and R 15 are each independently H or C 1 to C 6 alkyl.