申请人:GLAXO GROUP LIMITED
公开号:EP0220054A2
公开(公告)日:1987-04-29
The present invention provides compounds of the general formula (I)
wherein
Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms, or the groups C1-6alkyl, nitro, -(CH2)qR, [where R is hydroxy, C1-6 alkoxy, -NR3R4 (where R3 and R4 each represents a hydrogen atom, or a C1-4 alkyl group, or -NR3R4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from -O- or -S-or a group -NH- or -N(CH3)-), -NR5COR6 (where R5 represents a hydrogen atom or a C1-4 alkyl group, and R6 represents a hydrogen atom or a C1-4 alkyl, Ci-4 alkoxy, phenyl or -NR3R4 group), -NRSS02R7 (where R7 represents a C1-4 alkyl, phenyl or -NR3R4 group), -COR8 (where R8 represents hydroxy, C1-4alkoxy or-NR3R4), -SR9 (where R9 is a hydrogen atom, or a C1-4 alkyl or phenyl group), -SOR9, -S02R9, or -CN, and q represents an integer from 0 to 3], or -O(CH2)1R10 [where R10 represents a hydroxy or C1-4 alkoxy group, and t is an integer 2 or 3], or Ar is a phenyl group substituted by an alkylenedioxy group of formula -O(CH2)pO-, where p represents an integer 1 or 2:
R1 and R2 each represents a hydrogen atom or a C1-3 alkyl group with the proviso that the sum total of carbon atoms in R1 and R2 is not more than 4;
X represents a bond or a C1-7 alkylene, C2-7 alkynylene or C2-7 alkenylene chain and
Y represents a bond or a C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is 2-10;
Q represents the group
[where Q1 represents C1-3 alkoxy, methanesulphonyl or cyano) or the group -CH2NHR11 (where R11 represents R12CO-. R12NHCO-. R12R13NSO2- or R14SO2-, where R12 and R13 each represent a hydrogen atom or a C1-3 alkyl group, and R14 represents a C1-3 alkyl group), or the group -NR15R16 (where R15 represents a hydrogen atom or a C1-4alkyl group, and R16 represents a hydrogen atom or a C1-4alkyl group or, when R15 is a hydrogen atom. R16 also represents a C1-4 alkoxycarbonyl group)]. or Q represents the group
or Q represents a phenyl group substituted by a hydroxy group and optionally also by a halogen atom;
and physiologically acceptable salts and solvates (e.g. hydrates)thereof.
The compounds have a stimulant action at β2-adrenorecep- tors and may be used in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.
本发明提供通式 (I) 的化合物
其中
Ar 代表可任选被一个或多个取代基取代的苯基,这些取代基可选自卤素原子、或 C1-6 烷基、硝基、-(CH2)qR、[其中 R 是羟基、C1-6 烷氧基、-NR3R4(其中 R3 和 R4 各代表一个氢原子或一个 C1-4 烷基、或 -NR3R4 形成饱和杂环氨基,该氨基有 5-7 个环成员,并可选择在环中包含一个或多个选自 -O- 或 -S- 或基团 -NH- 或 -N(CH3)- 的原子),-NR5COR6(其中 R5 代表氢原子或 C1-4 烷基、R6代表氢原子或C1-4烷基、Ci-4烷氧基、苯基或-NR3R4基团)、-NRSS02R7(其中R7代表C1-4烷基、苯基或-NR3R4基团)、-CORR8(其中R8代表羟基、C1-4烷氧基或-NR3R4基团)、-SR9(其中R9为氢原子或C1-4烷基或苯基)、-SOR9、-S02R9 或-CN,且 q 代表 0 至 3 的整数],或-O(CH2)1R10[其中 R10 代表羟基或 C1-4 烷氧基,且 t 代表 2 或 3 的整数],或 Ar 是被式 -O(CH2)pO- 的烷二氧基取代的苯基,其中 p 代表 1 或 2 的整数:
R1 和 R2 各代表一个氢原子或一个 C1-3 烷基,但 R1 和 R2 中的碳原子总数不超过 4;
X 代表键或 C1-7 亚烷基、C2-7 亚炔基或 C2-7 烯基链,以及
Y 代表键或 C1-6 亚烷基、C2-6 亚烯基或 C2-6 亚炔基链,但 X 和 Y 中碳原子的总和为 2-10;
Q 代表以下基团
[其中 Q1 代表 C1-3 烷氧基、甲磺酰基或氰基)或基团 -CH2NHR11 (其中 R11 代表 R12CO-。R12NHCO-.R12R13NSO2-或 R14SO2-,其中 R12 和 R13 各自代表氢原子或 C1-3 烷基,R14 代表 C1-3 烷基),或基团 -NR15R16 (其中 R15 代表氢原子或 C1-4 烷基,R16 代表氢原子或 C1-4 烷基,或当 R15 为氢原子时,R16 还代表 C1-4 烷基。或 Q 代表以下基团
或 Q 代表被羟基和卤原子取代的苯基;
及其生理上可接受的盐和溶液(如水合物)。
这些化合物对 β2-肾上腺素受体有刺激作用,可用于治疗与可逆性气道阻塞有关的疾病,如哮喘和慢性支气管炎。