Patent GB-1509527-A (GB)
Title: 1-(aryl-or heteroaryl)oxy-3-(substituted-amino)propan-2-ol derivatives processes for their manufacture and pharmaceutical compositions containing them
IPC: C07D239/34
Filed: 1974-06-05
Abstract: 1509527 1 - Aryl or heteroaryloxy - 3- substituted amino propan-2-ols, their preparation and their pharmaceutical compositions IMPERIAL CHEMICAL INDUSTRIES Ltd 28 May 1975 [5 June 1974] 24837/74 Addition to 1455116 Heading C2C The invention comprises compounds of the general Formula (I) wherein A represents a C 2-12  alkylene group; X represents a carbonyl or sulphonyl group; Y represents a direct bond or C 1-6  alkylene, C 1-6  oxyalkylene, C 1-6  alkyleneoxy, imino, C 1-6  alkylimino, C 1-6  iminoalkylene, C 1-6  iminoalkylenoxy or C 1-6  iminoalkylenecarbonyloxy radical or, when R<SP>1</SP> is other than hydrogen, an oxygen atom and either (a), R represents an optionally substituted heterocyclic ring system or an aryl radical of Formula (Ia) and R<SP>1</SP> represents an optionally substituted heterocylic ring system or an aryl radical of Formula (Ib) wherein R<SP>2</SP>, R<SP>3</SP>, R<SP>12</SP> and R<SP>13</SP> are independently a H or halogen atom or an OH, NH 2 , NO 2 , CN, C 1-6  alkyl, C 1-6  hydroxyalkyl, C 3-6  cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkythio, C 3-6  cycloalkoxy, C 2-6  alkenyloxy, C 2-6  alkynyloxy or C 2-6  alkanoyl, radical or an aryl, aryloxy or dialkylamino radical of up to 12 carbon atoms or wherein R<SP>2</SP> and R<SP>3</SP> and/or R<SP>12</SP> and R<SP>13</SP> together form a -(CH 2 ) 3 -; -(CH 2 ) 4 -; radical, and R<SP>4</SP> represents H or an amidic radical selected from wherein X is as defined above; Q is a direct bond or a C 1-6  alkylene or C 2-6  alkenylene group; Q<SP>1</SP> is C 1-6  alkylene; R<SP>15</SP> is H or a C 1-6  alkyl group and R<SP>16</SP> is H or a C 2-6  alkenyl, C 3-6  cycloalkyl, C 1-6  hydroxyalkyl or C 2-6  alkoxyalkyl group or an alkyl, aryl, aralkyl or aralkenyl group of up to 10 carbon atoms and wherein R<SP>14</SP> is an amidic radical as defined above for R<SP>4</SP> or (b) R is an optionally substituted heterocyclic ring system and R<SP>1</SP> is a hydrogen atom or an alkyl, haloalkyl, alkenyl or cycloalkyl group having up to 10 carbon atoms or an aryl radical of Formula Ic wherein R<SP>12</SP> and R<SP>13</SP> are as defined above or an acid additive salt thereof which may be prepared by processes known in the art in order to assemble the fine radicals (i) R-O; (iii) -NR<SP>6</SP>-; (iv) -A-NR<SP>7</SP>- and (v) -X-Y-R<SP>1</SP> where R, R<SP>1</SP>, A, X and Y are as defined above and R<SP>5</SP>, R<SP>6</SP> and R<SP>7</SP> are H or a protecting group and, when any of R<SP>5</SP>, R<SP>6</SP> and R<SP>7</SP> is a protecting group, removing said group # - Isonicotinamidoethylamine, # - 2 - thenamidoethylamine and # - 2 - furamidoethylamine are prepared by reaction of the ethyl ester of the corresponding heterocyclic acid with ethylene diamine and are converted respectively into their hydrochloride, oxalate and hydrochloride salts. # - (4 - Carbamoylmethylphenoxyacetamido)- ethylamine and # - (4 - acetamidophenoxyacetamido)ethylamine are prepared by reaction of ethylene diamine with the ethyl esters of the corresponding substitued phenoxyacetic acids. 3 - # - (p - Acetamidobenzenesulphonamido)- N - benzyl - ethylamino - 1 - phenoxy - 2 - propanol is prepared by reaction of p-acetamidobenzenesulphonylchloride with 1-#-(N-benzylamino)ethylamino - 3 - phenoxy - 2 - propanol. Ethyl - 4 - acetamidomethylphonoxyacetate is prepared by reacting 4-acetamidomethylphenol with ethylbromoacetate. 3 - (# - Aminoethylamino) - 1 - (benzadioxan- 5 - yloxy) - 2 - propanol is prepared by reacting 1 - (benzodioxan - 5 - yloxy) - 2,3 - epoxypropane with ethylene diamine. 3 - # - (p - Benzyloxyphenozyacetamido) - ethylamino - 1 - (benzodioxan - 5 - yloxy) - 2- propanol is prepared by reaction of #-(pbenzyloxyphenoxyacetamido)ethylamine with 1-(benzodioxan-5-yloxy)-2,3-epoxypropane. 1 - (2 - Benzylozyphenozy) - 3 - (# - 2 - furamidoethyl)amino - 2 - propanol is prepared by reacting 1 - (2 - benzoyloxyphenoxy) - 2,3- epoxypropane with #-(2-foramido)ethylamine. Pharmaceutical compositions having #-adrenegenie blocking activity for oral or intravenous administration comprise a compound of Formula I or an acid additive salt thereof and a pharmaceutically acceptable diluent or carrier.