Treatment of disorders associated with pulmonary hypertension and/or right heart failure

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): ##STR1## wherein A.sup.1 represents CR.sub.1, N or N.sup.+ --O.sup.- ; when A.sup. 1 represents N or N.sup.+ --O.sup.-, R.sup.2 represents hydrogen;P Pwhen A.sup.1 represents CR.sub.1 then: PPeither; PPone of R.sub.1 and R.sub.2 is hydrogen and the other is a group R.sup.a wherein R.sup.a is selected from the class of C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxycarbonyl, C. sub.1-6 alkylcarbonyloxy, C. sub.1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C.sub. 1-6 alkylsulphinyl, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkylsulphinyl, C. sub.1-6 alkoxysulphonyl, C. sub.1-6 alkylcarbonylamino, C.sub.1-6 alkoxycarbonylamino, C.sub.1-6 alkyl-thiocarbonyl, C.sub.1-6 alkoxy- thiocarbonyl, C.sub.1-6 alkyl- thiocarbonyloxy, C.sub.1-6 alkyl- thiolmethyl, formyl or amionosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C.sub.1-6 alkyl groups, or C.sub.1-6 alkylsulphinylamino, C.sub.1-6 alkylsulphonylamino C.sub.1-6 alkoxysulphinylamino or C.sub.1-6 alkoxysulphonylamino or ethylenyl terminally substituted by C.sub.1-6 alkylcarbonyl, nitro or cyano, or -- C(C.sub.1-6 alkyl)NOH or --C(C.sub.1- 6 alkyl)NHN.sub.2,PP or;PPone of R.sub.1 and R.sub.2 is nitro, cyano or C.sub. 1-3 alkylcarbonyl and the other is a group R.sup.b wherein R.sup.b is methoxy or amino optionally substituted by one or two C.sub.1-6 alkyl or by C.sub.2-7 alkanoyl;PP one of R.sub.3 and R.sub.4 is hydrogen or C.sub.1-4 alkyl and the other is C.sub.1-4 alkyl or R.sub.3 and R.sub.4 together are C.sub.2-5 polymethylene;PPeither R.sub.5 is hydrogen, hydroxy, C. sub.1-6 alkoxy or C.sub.1-7 acyloxy and R.sub.6 is hydrogen or R.sub.5 and R.sub.6 together are abond;P PR.sub.7 is hydrogen, C. sub.1-6 alkyl optionally substituted by hydroxy, C.sub.1-6 alkoxy, C.sub. 1-6 alkoxycarbonyl or carboxy, C.sub.1- 6 alkyl substituted by halogen, or C.sub.2-6 alkenyl; aryl or heteroaryl either being optionally substituted by one or more groups or atoms selected from the class of C.sub.1-6 alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, C.sub.1-12 carboxylic acyl, or amino or aminocarbonyl optionally substituted by one or two C.sub.1-6 alkyl groups; PPR.sub.8 is hydrogen or C. sub.1-6 alkyl; orP PR.sub.7 and R.sub.8 are joined together to form C.sub.3-4 polymethylene or --CH.sub.2 --(CH.sub.2).sub.n --Z--(CH.sub.2)m-- wherein m and n represent zero or 1 or 2 such that m+n is 1 or 2, and Z is oxygen, sulphur or NR.sub.9 wherein R.sub.9 is hydrogen, C.sub.1-9 alkyl, C.sub. 2-7 alkanoyl, phenyl C.sub.1-4 alkyl, naphthylcarbonyl, phenylcarbonyl or benzylcarbonyl optionally substituted in the phenyl or naphthyl ring by one or two C.sub.1-6 alky, C.sub.1-6 alkoxy or halogen; mono- or bi- cyclicheteroarylcarbonyl;PP X is oxygen or sulphur; PPor a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.