申请人:Glaxo Group Limited
公开号:US04937268A1
公开(公告)日:1990-06-26
This invention relates to compounds of the general formula (I) and physiologically acceptable salts and solvates thereof wherein Ar represents ##STR1## where R.sup.3 is a bond or a straight or branched C.sub.1-2 alkylene group, R.sup.4 is a hydroxy group or a group R.sup.5 NH-- where R.sup.5 represents a group CH.sub.3 SO.sub.2 --, HCO-- or NH.sub.2 CO--, ##STR2## where R.sup.6 is a chlorine atom or the group F.sub.3 C--, ##STR3## k represents an integer from 1 to 8, m represents zero or an integer from 2 to 7 and n represents an integer from 2 to 7 with the proviso that the sum total of k, m and n is 4 to 12; R.sup.1 and R.sup.2 each represents a hydrogen atom or a methyl or ethyl group with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 2; R.sup.30 represents hydrogen or C.sub.1-2 alkyl; X represents an oxygen or sulphur atom; and Y and Q may each represent a bond or an oxygen or sulphur atom with the provisos that at least one of Y and Q represents an oxygen or sulphur atom and when Y is a bond m is zero, or when Y represents an oxygen or sulphur atom m is an integer from 2 to 7; P represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms, or the groups C.sub.1-3 alkyl, C.sub.1-3 alkoxy, hydroxy, --CH.sub.2 OH--, --(CH.sub.2).sub.2 OH, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 (CH.sub.2).sub.2 CH.sub.3, --R.sup.7, COR.sup.7, --NHCOR.sup.8 and --NR.sup.9 SO.sub.2 R.sup.10 ; where R.sup.7 represents an amino, aminoC.sub.1-3 alkyl, aminoC.sub.1-3 dialkyl, pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-methylpiperazino or morpholino group; R.sup.8 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy, phenyl or amino group; R.sup.9 represents a hydrogen atom or a methyl group; R.sup.10 represents a methyl, phenyl, amino or dimethylamino group; or P represents a pyridyl group optionally substituted by one or two substitutents selected from halogen atoms or hydroxy, C.sub.1-3 alkyl and C.sub.1-3 alkoxy groups. The compounds have a stimulant action at .beta..sub.2 -adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.
本发明涉及一般式(I)的化合物及其生理上可接受的盐和溶剂化物,其中Ar代表##STR1##其中R.sup.3是键或直链或支链C.sub.1-2烷基,R.sup.4是羟基或R.sup.5 NH--基团,其中R.sup.5代表CH.sub.3 SO.sub.2 --,HCO--或NH.sub.2 CO--,##STR2##其中R.sup.6是氯原子或F.sub.3 C--基团,##STR3##k表示1至8的整数,m表示零或2至7的整数,n表示2至7的整数,但k、m和n的总和为4至12;R.sup.1和R.sup.2分别表示氢原子或甲基或乙基基团,但R.sup.1和R.sup.2中的碳原子总数不超过2;R.sup.30代表氢或C.sub.1-2烷基;X代表氧或硫原子;Y和Q可以分别表示键或氧或硫原子,但至少有一个Y和Q表示氧或硫原子,当Y是键时,m为零,或当Y表示氧或硫原子时,m为2至7的整数;P表示苯基,可选地取代一个或多个从卤原子中选择的取代基,或羟基,--CH.sub.2 OH--,--(CH.sub.2).sub.2 OH,--CO.sub.2 H,--CO.sub.2 CH.sub.3,--CO.sub.2(CH.sub.2).sub.2 CH.sub.3,--R.sup.7,COR.sup.7,--NHCOR.sup.8和--NR.sup.9 SO.sub.2 R.sup.10;其中R.sup.7表示氨基,氨基C.sub.1-3烷基,氨基C.sub.1-3二烷基,吡咯烷基,哌啶基,己亚甲基亚胺基,哌嗪基,N-甲基哌嗪基或吗啉基团;R.sup.8表示氢原子或C.sub.1-4烷基,C.sub.1-4烷氧基,苯基或氨基团;R.sup.9表示氢原子或甲基基团;R.sup.10表示甲基,苯基,氨基或二甲基氨基基团;或P表示吡啶基,可选地取代一个或两个从卤原子或羟基,C.sub.1-3烷基和C.sub.1-3烷氧基中选择的取代基。这些化合物在β.sub.2-肾上腺素受体上具有刺激作用,特别适用于治疗可逆性气道阻塞相关疾病,如哮喘和慢性支气管炎。