Phenothiazone derivatives and analogs

Abstract

Abstract Phenothiazine compounds of formula where X is in the 1 or 3 position and is O, S or NR; R is H, C 1 -C 6 branched or linear alkyl, CN or phenyl; Y is 0, Se, S, SO, SO 2 or NR; and the broken line represents an optional double bond between the 1 and 2 or 2 and 3 position; each of R 1 , R 2 , R 3 and R 4 , independently of the others, is (1) hydrogen (2) C 1-6 alkyl, (3) C 2-6 alkenyl, (4) -(CH 2 ) n M where n is 0 or an integer from 1 to 6 and M is (a) OR 5 , (b) halogen, (c) CF 3 , (d) SR 5 where R 5 is H; alkoxyalkyl; acyloxyalkyl; C 1-6 alkyl; benzyl; phenyl or substituted phenyl where the substituents are C 1-3 alkyl, halogen, CN, CF 3 , COOR 6 , CH 2 COOR 6 , (CH 2 ) n NR 8 R 9 where n is 0, 1 or 2, C 1-3 alkoxy, OH, C 1-6 haloalkyl, -(CH 2 ) m COOR 6 , where m is 0 or an integer from 1 to 6 and R 6 is H, phenyl or C 1-6 alkyl; CN, formyl; perfluoroalkyl; or CH 2 -R 12 , where R 12 is C 1-5 alkyl, phenyl or dimethylamino; (e) phenyl or substituted phenyl as defined above for R 5 ; (f) COOR 6 ; (g) where R 14 is H, (CH 2 ) n COOR 6 where n is 0 or an integer from 1 to 4, C 1-6 alkyl, CF 3 , phenyl, or substituted phenyl as defined above for R 5 ; (h) tetrazole; (i) where R 7 is C 1-8 alkyl, benzyl or phenyl; (j) -NR 8 R 9 where R e and R 9 are independently selected from H, phenyl or substituted phenyl as defined above for R 5 , C 1 -C 4 alkyl or C 1 -C 4 alkylaminoalkyl, or are joined through the N to form a heterocycloalkyl of 5-8 ring atoms; (k) -NHSO 2 R 10 where R 10 is OH, C 1 -C 6 alkyl, C 1 -C 6 - alkoxy, phenyl or CF 3 ; (m) -SOR 11 where R 11 is C 1 -C 6 alkyl, phenyl or substituted phenyl as defined above for R 5 , (CH 2 ) m COOR 6 where m is 1 to 6, CN, formyl or C 1-4 perfluoroalkyl; (p) -SO 2 R 13 where R 13 is OH, H, C 1 -C 6 alkyl, phenyl or substituted phenyl as defined above for R 5 , (CH 2 ) m COOR 6 where m is 1 to 6, CN or C 1-4 perfluoroalkyl; (q) NO 2 ; (r) (s) (t) (u) -CN; or (v) NR 15 R 16 where R 15 and R 16 are such that HNR 15 R 16 is an essential amino acid; or any two of R 1 , R 2 , R 3 and R 4 are joined to form a fourth saturated or unsaturated C 5-6 ring, and T is H, halogen or CF 3 . are useful as inhibitors of mammalian leukotriene biosynthesis and therefore are useful therapeutic agents for treatng pain, skin conditions, allergic conditions, pulmonary conditions, asthma, cardiovascular disorders and inflammation. They are included in pharmaceutical compositions. Certain of the compounds are novel.

Inventors

• 👤 Yvan Guindon
• 👤 Rejean Fortin
• 👤 Cheuk K. Lau
• 👤 Joshua Rokach
• 👤 Christiane Yoakim

Bibliographic Details