申请人:GLAXO GROUP LIMITED
公开号:EP0220878A2
公开(公告)日:1987-05-06
he invention provides compounds of the general formula
wherein
Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms, or the groups C1-6 alkyl, 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 R6 represents a hydrogen atom or a C1-4 alkyl group, and R6 represents a hydrogen atom or a C1-4 alkyl, C1-4 alkoxy, phenyl or -NR3R4 group). -NR5S02R7 (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(CH21R11 [where R" represents a hydroxy or C1-4 alkoxy group and t is 2 or 3], or Ar is a phenyl group substituted by an alkylenedioxy group of formula -O(CH2)pO-, where p represents 1 or 2;
R' and R2 each represent 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;
R20 represents a C1-3 alkyl group;
X represents a C2-8 alkylene C2-8 alkenylene or C2-8alkynylene chain, and
Y represents a C1-7 alkylene C2-7 alkenylene or C2-7alkynylene chain. with the proviso that the sum total of carbon atoms in X
and Y is 4 to 12; Q represents (a)
EMI PA=2 FR= 1 HE=30 WI=40 TI=CHE (where R'2 is a straight or branched C1-3 alkylene group).
(where one of R13 and R14 is a hydroxy group and the other is a hydrogen or halogen atom or a hydroxy group),
[where R15 is a group R16CO-, R16NHCO-, R16R17NSO2- or R18SO2- (where R'6 and R17 is each a hydrogen atom or a C1-3alkyl group and R18 is a C1-3 alkyl group) and p is an integer 0 or 1],
(where R26 and R27 is each a hydrogen atom or a C1-3 alkyl group or. when R26 is a hydrogen atom, R27 may also be a C1-4alkoxycarbonyl group),
(where R19 is a C1-3 alkyl group),
or (i)
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.
本发明提供了通式如下的化合物
式中
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 形成一个饱和杂环氨基,该氨基有 5-7 个环成员,并可选在环中包含一个或多个选自 -O- 或 -S- 或一个基团 -NH- 或 -N(CH3)-)的原子、-NR5COR6(其中 R6 代表氢原子或 C1-4 烷基,R6 代表氢原子或 C1-4 烷基、C1-4 烷氧基、苯基或 -NR3R4 基团)。-NR5S02R7(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)、-SR9(其中 R9 是氢原子或 C1-4 烷基或苯基)。-SOR9、-S02R9 或 -CN,且 q 代表 0 至 3 的整数],或 -O(CH21R11 [其中 R" 代表羟基或 C1-4 烷氧基且 t 为 2 或 3],或 Ar 是被式 -O(CH2)pO- 的亚烷基二氧基取代的苯基,其中 p 代表 1 或 2;
R' 和 R2 各自代表氢原子或 C1-3 烷基,但 R1 和 R2 中的碳原子总数不超过 4;
R20 代表 C1-3 烷基;
X 代表 C2-8 亚烷基 C2-8 亚烯基或 C2-8 亚炔基链,以及
Y代表C1-7亚烷基 C2-7烯基或C2-7炔基链。
和 Y 中碳原子的总和为 4 至 12; Q 代表 (a)
EMI PA=2 FR= 1 HE=30 WI=40 TI=CHE (其中 R'2 是直链或支链 C1-3 亚烷基)。
(其中 R13 和 R14 中的一个是羟基,另一个是氢原子、卤素原子或羟基)、
[其中 R15 为基团 R16CO-、R16NHCO-、R16R17NSO2- 或 R18SO2-(其中 R'6 和 R17 各为氢原子或 C1-3 烷基,R18 为 C1-3 烷基),p 为整数 0 或 1]、
(其中 R26 和 R27 各为氢原子或 C1-3 烷基,或当 R26 为氢原子时,R27 也可以是 C1-4 烷氧基羰基)、
(其中 R19 为 C1-3 烷基)、
或 (i)
及其生理上可接受的盐类和溶剂(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。