Patent ES-8802144-A1 (ES)
Title: Leukotriene biosynthesis inhibitors.
IPC: A61K31/535
Filed: 1984-10-04
Abstract: Phenothiazine derivatives and their analogs having the Formula I, and salts of such compounds, are useful as inhibitors of the biosynthesis of mammalian leukotrienes. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation, and are useful as cytoprotective agents, and are made into pharmaceutical compositions. Certain of the compounds are novel. In Formula I: <CHEM contiene="yes"> X is Se, S, SO, SO2 or O R<1> is H C1-6-alkyl C1-6acyl (C1-6acyloxy)-(C1-6alkyl) (C1-6-alkoxy)-(C1-6alkyl) benzoyl substituted benzoyl having C1-3alkyl, halogen, CN, CF3, COOR<6>, CH2COOR<6>, (CH2)nNR<8>R<9>, where n is 0, 1 or 2, C1-3alkoxy, and/or OH substitution, (herein called 'substituted as herein defined') carbamoyl CO-NHR<7> COOR<7> p-toluenesulfonyl methanesulfonyl and acyl group such that R<1>-OH is an essential amino acid benzyl phenethyl (CH2)pOR<a> where R<a> is C1-6alkyl or phenyl and p is an integer from 1 to 5 (CH2)nCOOR<6> where n is 0, 1 or 2 or (C1-6acyloxy)-(C1-6alkoxy)carbonyl each of R<2>, R<3>, R<4> and R<5>, independently of the others, is hydrogen C1-6alkyl C2-6alkenyl or -(CH2)qM where q is 0 or an integer from 1 to 6 and M is (a) -OR<1><6> (b) halogen (c) -CF3 (d) -SR<1><6> (e) phenyl or substituted phenyl as herein defined (f) COOR<6> (g) -CO-R<1><4> (h) tetrazolyl (i) -NH-CO-R<7> (j) -NR<8>R<9> (k) -NHSO2R<1><0> where R<1><0> is OH, C1-6alkyl, C1-6alkoxy or phenyl (l) -CO-CH2OH (m) -SOR<1><1> where R<1><1> is C1-6alkyl, phenyl, substituted phenyl as herein defined, (CH2)mCOOR<6> where m is an integer from 1 to 6, CN, formyl, or C1-4perfluoroalkyl (n) -CONR<8>R<9> (o) -SO2NR<8>R<9> (p) -SO2R<1><3> where R<1><3> is hydrogen, OH, C1-6alkyl, phenyl, substituted phenyl as herein defined, (CH2)mCOOR<6> where m is as defined above, CN, formyl, or C1-4 perfluoroalkyl (q) -NO2 (r) -O-CO-R<1><4> (s) O-CO-NR<8>R<9> or (t) -CN each R<6>, independently of the others, is hydrogen, C1-6alkyl or phenyl each R<7>, independently of the others, is C1-6alkyl, benzyl, phenyl or (C1-6acyloxy)-(C1-6alkyl) each R<8> and each R<9>, independently of any others, is hydrogen, C1-4acyl, phenyl, or substituted phenyl as herein defined or an R<8> and an R<9> are joined through the N to which they are both attached to form a heterocycloalkyl group having from 5 to 8 ring atoms each R<1><4>, independently of the others, is hydrogen, (CH2)rCOOR<6> where r is 0 or an integer from 1 to 4 C1-6alkyl C1-6alkoxy (C1-6acyloxy)-(C1-6alkoxy) phenyl substituted phenyl as herein defined or C1-6aminoalkyl such that R<1><4>COOH is an essential amino acid each R<1><6>, independently of any others, is hydrogen, (C1-5alkoxy)-(C1-5alkyl), C1-6alkyl benzyl (C1-6acyloxy)-(C1-6alkyl) phenyl substituted phenyl as herein defined -(CH2)mCOOR<6> where m is as defined above CN formyl perfluoroalkyl or CH2-R<1><2> where R<1><2> is C1-5alkyl, dimethylamino or phenyl and T is hydrogen or -OR15, where R15 is hydrogen, C1-6alkyl, (C1-6alkyl)-acyl, phenylacyl, substituted phenyl-acyl as herein defined benzoyl substituted benzoyl as herein defined or arylsulfonyl and compounds that are pharmaceutically acceptable salts thereof.