Chroman derivatives for treatment of pulmonary hypertension.

摘要

A method for the treatment and/or prophylaxis of disorders associated with pulmonary hypertension and/or disorders associated with right heart failure, in mammals, which method comprises administering to the mammal in need of such treatment and/or prophylaxis an effective and/or prophylactic, non-toxic, amount of a compound of formula (I): <CHEM> wherein A<1> represents CR1, N or N<+>-O<->; when A<1> represents N or N<+>-O<->, R<2> represents hydrogen; when A<1> represents CR1 then: either; one of R1 and R2 is hydrogen and the other is a group R<a> wherein R<a> is selected from the class of C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C1-6 alkylsulphinyl, C1-6 alkylsulphonyl, C1-6 alkoxysulphinyl, C1-6 alkoxysulphonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkyl-thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C1-6 alkyl-thiocarbonyloxy, C1-6 alkyl-thiolmethyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C1-6 alkyl groups, or C1-6 alkylsulphinylamino, C1-6 alkylsulphonylamino C1-6 alkoxysulphinylamino or C1-6 alkoxysulphonylamino or ethylenyl terminally substituted by C1-6 alkylcarbonyl, nitro or cyano, or -C(C1-6 alkyl)NOH or -C(C1-6 alkyl)NNH2, or; one of R1 and R2 is nitro, cyano or C1-3 alkylcarbonyl and the other is a group R<b> wherein R<b> is methoxy or amino optionally substituted by one or two C1-6 alkyl or by C2-7 alkanoyl; one of R3 and R4 is hydrogen or C1-4 alkyl and the other is C1-4 alkyl or R3 and R4 together are C2-5 polymethylene; either R5 is hydrogen, hydroxy, C1-6 alkoxy or C1-7 acyloxy and R6 is hydrogen or R5 and R6 together are abond; R7 is hydrogen, C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy, C1-6 alkoxycarbonyl or carboxy, C1-6 alkyl substituted by halogen, or C2-6 alkenyl;aryl or heteroaryl either being optionally substituted by one or more groups or atoms selected from the class of C1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C1-6 alkyl groups; R8 is hydrogen or C1-6 alkyl; or R7 and R8 are joined together to form C3-4 polymethylene or -CH2-(CH2)n-Z-(CH2)m- where m and n represent zero or 1 or 2 such that m+n is 1 or 2, and Z is oxygen, sulphur or NR9 wherein R9 is hydrogen,C1-9 alkyl, C2-7 alkanoyl, phenyl C1-4 alkyl, naphthylcarbonyl, phenylcarbonyl or benzylcarbonyl optionally substituted in the phenyl or naphthyl ring by one or two C1-6 alkyl, C1-6 alkoxy or halogen; mono- or bi-cyclicheteroarylcarbonyl; X is oxygen or sulphur; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.