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1. A method for the treatment of pulmonary arterial hypertension (PAH) and of pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD), of chronic-obstructive pulmonary diseases (COPD), of acute lung injury (ALI), of acute respiratory distress syndrome (ARDS), of pulmonary emphysema, of alpha-1 antitrypsin deficiency (AATD), of cystic fibrosis (CF) and of bronchiectasia, comprising administering an effective amount of a compound of formula (I) to a human or animal in need thereof, wherein the compound of formula (I) is: in which A and E both represent C—R7 or one of the two ring members A and E represents N and the other represents C—R7, in which R7 represents in each case hydrogen, fluorine or chlorine, Z represents O or S, n represents the number 0, 1 or 2, R1 represents (C1-C6)-alkyl which may be substituted by hydroxyl, (C1-C4)-alkoxy, amino, mono- or di-(C1-C4)-alkylamino, hydroxycarbonyl, aminocarbonyl, (C3-C6)-cycloalkyl, phenyl or 5- or 6-membered heteroaryl or up to five times by fluorine, or represents (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, phenyl or 5- or 6-membered heteroaryl, where the (C3-C6)-cycloalkyl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of (C1-C4)-alkyl, hydroxyl and (C1-C4)-alkoxy and the phenyl and heteroaryl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C1-C4)-alkyl, difluoromethyl, trifluoromethyl, (C1-C4)-alkoxy, difluoromethoxy and trifluoromethoxy, R2 represents hydrogen, fluorine or chlorine, R3 represents cyano or a group of the formula —C(═O)—R8, —C(═O)—O—R8, —C(═O)—NH2 or —C(═O)—NH—R8, in which R8 represents (C1-C6)-alkyl, (C3-C6)-alkenyl or (C3-C6)-cycloalkyl, where (C1-C6)-alkyl and (C3-C6)-cycloalkyl for their part may be substituted up to two times by identical or different substituents from the group consisting of hydroxyl, (C1-C4)-alkoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, amino, mono- and di-(C1-C4)-alkylamino and in (C1-C6)-alkyl and (C3-C6)-cycloalkyl in each case one CH2 group may be replaced by an oxygen atom, if this results in a chemically stable compound, R4 represents methyl or ethyl or R3 and R4 are attached to one another and together form a fused group of the formulain which
* denotes the point of attachment to the 5-position, shown in formula (I), of the dihydropyrimidine ring and ** denotes the point of attachment to the 6-position, shown in formula (I), of the dihydropyrimidine ring and R9 represents hydrogen, (C1-C6)-alkyl or (C3-C6)-cycloalkyl, where (C1-C6)-alkyl may be substituted by hydroxyl, (C1-C4)-alkoxy, aminocarbonyl, aminocarbonylamino, (C1-C4)-acylamino or (C3-C6)-cycloalkyl, R5 represents hydrogen or (C1-C6)-alkyl which may be substituted by cyano, hydroxyl, (C1-C4)-alkoxy, amino, mono- or di-(C1-C4)-alkylamino or (C3-C6)-cycloalkyl or up to three times by fluorine, or represents phenyl, pyridyl or pyrimidinyl, where phenyl, pyridyl and pyrimidinyl for their part may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C1-C4)-alkyl, trifluoromethyl, (C1-C4)-alkoxy and trifluoromethoxy, or R5 represents a group of the formula —C(═O)—O—R10, -L1-C(═O)—O—R11, -L2-C(═O)—NR12R13, -L2-SO2—NR12R13, -L2-C(═O)—NR14—NR12R13 or -L2-SO2—R15, in which L1 represents (C1-C6)-alkanediyl, L2 represents a bond or (C1-C6)-alkanediyl, R10 represents (C1-C6)-alkyl which may be substituted by (C3-C6)-cycloalkyl or phenyl, R11 represents hydrogen or (C1-C6)-alkyl which may be substituted by (C3-C6)-cycloalkyl or phenyl, R12 and R13 are identical or different and independently of one another represent hydrogen, (C1-C6)-alkyl, (C3-C6)-cycloalkyl or 4- to 6-membered heterocyclyl, where (C1-C6)-alkyl, (C3-C6)-cycloalkyl and 4- to 6-membered heterocyclyl for their part may be substituted up to two times by identical or different substituents from the group consisting of fluorine, hydroxyl, (C1-C4)-alkoxy, oxo, amino, mono- or di-(C1-C4)-alkylamino, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl and aminocarbonyl and in (C1-C6)-alkyl a CH2 group may be replaced by an oxygen atom, if this results in a chemically stable compound, and (C3-C6)-cycloalkyl and 4- to 6-membered heterocyclyl may additionally be substituted up to two times by identical or different (C1-C4)-alkyl radicals, which for their part may be substituted by hydroxyl, (C1-C4)-alkoxy or hydroxycarbonyl, or R12 and R13 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocycle which may contain a further ring heteroatom from the group consisting of N, O, S, SO and SO2 and which may be substituted up to two times by identical or different substituents from the group consisting of (C1-C4)-alkyl, hydroxyl, (C1-C4)-alkoxy, oxo, amino, mono- or di-(C1-C4)-alkylamino, hydroxycarbonyl, aminocarbonyl, (C3-C6)-cycloalkyl, 4- to 6-membered heterocyclyl and 5- or 6-membered heteroaryl, where (C1-C4)-alkyl for its part may be substituted by hydroxyl, (C1-C4)-alkoxy or hydroxycarbonyl, R14 represents hydrogen or (C1-C4)-alkyl and R15 represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, phenyl or 5- or 6-membered heteroaryl, where (C1-C6)-alkyl may be substituted by chlorine, hydroxyl, (C1-C4)-alkoxy, mono- or di-(C1-C4)-alkylamino or (C3-C6)-cycloalkyl or up to three times by fluorine and phenyl and 5- or 6-membered heteroaryl for their part may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C1-C4)-alkyl, difluoromethyl, trifluoromethyl, (C1-C4)-alkoxy and trifluoromethoxy, and R6 represents hydrogen, fluorine or chlorine, or a physiologically acceptable salt thereof. |
