Aminophenol derivatives
AssigneeGlaxo Group Limited
InventorsIan F. Skidmore, Harry Finch, Alan Naylor, Lawrence H. C. Lunts, Ian B. Campbell
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Abstract
The invention provides compounds of the general formula (I) ##STR1## wherein Ar, R.sup.1, R.sup.2, X, Y and Q are defined in the specification and physiologically acceptable salts and solvates thereof. The compounds have a selective stimulant action at .beta..sub.2 -adrenoreceptors and may be used, inter alia, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.
Claims16
A compound of formula (I) ##STR20## wherein Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms, or the groups C.sub.1-6 alkyl, C.sub.1-6 alkoxy, nitro, --(CH.sub.2).sub.q R, --(CH.sub.2).sub.r R.sup.10 or --O(CH.sub.2).sub.t R.sup.11, or Ar is a phenyl group substituted by an alkylenedioxy group of formula --O(CH.sub.2).sub.p O--;
- where R is hydroxy, --NR.sup.3 R.sup.4, --NR.sup.5 COR.sup.6, --NR.sup.5 SO.sub.2 R.sup.7, --COR.sup.8, --SR.sup.9, --SOR.sup.9, SO.sub.2 R.sup.9 or --CN;
- R.sup.1 and R.sup.2 each represent a hydrogen atom or a C.sub.1-3 alkyl group with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4;
- R.sup.3 and R.sup.4 each represents a hydrogen atom or a C.sub.1-4 alkyl group or --NR.sup.3 R.sup.4 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(CH.sub.3)--;
- R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group;
- R.sup.6 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy, phenyl or --NR.sup.3 R.sup.4 group;
- R.sup.7 represents a C.sub.1-4 alkyl, phenyl or --NR.sup.3 R.sup.4 group;
- R.sup.8 represents hydroxy, C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4 ;
- R.sup.9 is a hydrogen atom or a C.sub.1-4 alkyl or phenyl group;
- R.sup.10 is a C.sub.1-4 alkoxy group;
- R.sup.11 represents a hydroxy or C.sub.1-4 alkoxy group;
- p represents 1 or 2;
- q represents an integer from 0 to 3;
- r represents an integer from 1 to 3;
- t is 2 or 3;
- X represents a C.sub.1-7 alkylene, C.sub.2-7 alkenylene or C.sub.2-7 alkynylene chain;
- Y represents a bond, or a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is 2 to 10;
- Q represents a group R.sup.12 CO--, R.sup.12 NHCO, R.sup.12 R.sup.13 NSO.sub.2 --, or R.sup.14 SO.sub.2
- where R.sup.12 and R.sup.13 each represent a hydrogen atom or a C.sub.1-3 alkyl group, and R.sup.14 represents a C.sub.1-4 alkyl group;
- with the proviso that when X represents C.sub.1-7 alkylene, and Y represents a bond or C.sub.1-6 alkylene, then the group Ar does not represent an unsubstituted phenyl group or a phenyl group substituted by one or more substituents selected solely from halogen atoms or C.sub.1-6 alkyl or C.sub.1-6 alkoxy groups or an alkylenedioxy group --O(CH.sub.2).sub.p O;
- or a physiologically acceptable salt or solvate thereof.
A compound of formula (Ia) ##STR22## or a physiologically acceptable salt or solvate thereof wherein X represents a C.sub.1-7 alkylene, C.sub.2-7 alkenylene or C.sub.2-7 alkynylene chain;
- Y represents a bond, or a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain with the proviso that the sum total of carbon atoms in the chains X and
- Y is 5, 6 or 7;
- R.sup.1 and R.sup.2 each independently represent a hydrogen atom or a methyl group;
- Q represents HCO--, NH.sub.2 CO--, (CH.sub.3).sub.2 NSO.sub.2 -- or CH.sub.3 SO.sub.2 --;
- and
- Ar represents a phenyl group substituted by a group selected from amino, dimethylamino, nitro, morpholino, (CH.sub.2).sub.q NHCOR.sup.6, --NHSO.sub.2 R.sup.7, --COR.sup.8, --CH.sub.2 CONR.sup.3 R.sup.4, --SR.sup.9 or --(CH.sub.2).sub.r R.sup.10 ;
- where R.sup.6 is C.sub.1-4 alkyl and q is zero or 1, R.sup.7 is C.sub.1-4 alkyl, R.sup.8 is C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4 where R.sup.3 and R.sup.4 are both C.sub.1-4 alkyl or --NR.sup.3 R.sup.4 in the group --CONR.sup.3 R.sup.4 may also form a piperidino ring, R.sup.9 is C.sub.1-4 alkyl, and R.sup.10 is C.sub.1-4 alkoxy and r is 3;
- or Ar is 3,5-dihydroxyphenyl or 3-methoxy-4-hydroxyphenyl, or, when X and/or Y represent an alkenylene or alkynylene group, Ar may additionally repesent a phenyl group optionally substituted by a fluorine atom.
N,N-Diethyl-4-[4-[[6-[[2-hydroxy-2-[4-hydroxy-3-[(methylsulphonyl)amino ]phenyl]ethyl]amino]hexyl]oxy]butyl]benzamide or a physiologically acceptable salt or hydrate thereof.
A compound selected from:
- N-[2-hydroxy-5-[1-hydroxy-2-[[6-[4-(3,5-dihydroxyphenyl)butoxy]hexyl]amino] ethyl]phenyl]methanesulphonamide;
- N-[2-hydroxy-5-[1-hydroxy-2-[[6-[4-(4-hydroxy-3-methoxyphenyl)butoxy]hexyl] amino]ethyl]phenyl]methanesulphonamide;
- N-[2-hydroxy-5-[1-hydroxy-2-[[6-[4-(4-(methylthio)phenyl]butoxy]hexyl]amino ]ethyl]phenyl]methanesulphonamide;
- N-[2-hydroxy-5-[1-hydroxy-2-[[6-[4-(4-nitrophenyl)butoxy]hexyl]amino]ethyl] phenyl]methanesulphonamide;
- N-[5-[2-[[6-[4-(4-aminophenyl)butoxy]hexyl]amino-1-hydroxyethyl]-2-hydroxyp henyl]methanesulphonamide;
- propyl 4-[4-[[5-[[2-hydroxy-2-[4-hydroxy-3-[(methylsulphonyl)amino]phenyl]ethyl]a mino]pentyl]oxy]butyl]benzoate;
- N-[[4-[4-[[6-[[2-hydroxy-2-[4-hydroxy-3-[(methylsulphonyl)amino]phenyl]ethy l]amino]hexyl]butyl]phenyl]methyl]pentanamide;
- N-[2-hydroxy-5-[1-hydroxy-2-[[5-[4-[4-(3-methoxypropyl)phenyl]butoxy]pentyl ]amino]ethyl]phenyl]formamide;
- N-[4-[4-[[6-[[2-[3-[(aminocarbonyl)amino]-4-hydroxyphenyl]ethyl]amino]hexyl ]oxy]butyl]phenyl]butanesulphonamide;
- N-[2-hydroxy-5-[1-hydroxy-2-[[6-(4-phenylbutoxy)-3-hexynyl]amino]ethyl]phen yl]methanesulphonamide;
- (E)-N-[2-hydroxy-5-[1-hydroxy-2-[[6-[[4-(4-fluorophenyl)-3-butenyl]oxy]hexy l]amino]ethyl]phenyl]methanesulphonamide;
- and physiologically acceptable salts and hydrates thereof.
Dependencies are inferred from the claim text.