Patent GB-1435857-A (GB)
Title: Substituted sulphamides and pharmaceutical uses thereof
IPC: C07C67/00
Filed: 1974-09-19
Abstract: 1435857 Substituted sulphamides and pharmaceutical uses thereof BRISTOL-MYERS CO 19 Sept 1974 [20 Sept 1973] 40868/74 Heading C2C The invention comprises compounds of formula wherein R<SP>1</SP> is hydrogen, lower-alkyl of from 1 to 4 carbon atoms, cyclopropyl, phenyl, or tolyl; R<SP>2</SP> is hydrogen, lower alkyl of from 1 to 4 carbon atoms, cyclopropyl, or benzyl; or R<SP>1</SP> and R<SP>2</SP> may be joined to form with the nitrogen atom to which they are attached a 5 to 6 membered heterocyclic ring containing up to one additional heteroatom selected from oxygen and sulfur; R<SP>3</SP> is hydrogen, methyl, or ethyl; and R<SP>4</SP> is hydrogen, cyclopropyl, or lower alkyl of from 1 to 4 carbon atoms; or a pharmaceutically acceptable salt thereof. These compounds may be prepared by a process comprising the steps of (1) acylating a p-aminophenone having the formula wherein R<SP>3</SP> is as defined above, with an R<SP>1</SP>R<SP>2</SP>N- substituted sulfamoyl halide or azide to produce the corresponding p-sulfamidophenone, (2) halogenating the side chain of said p-sulfamidophenone to produce the corresponding sulfamidophenacyl halide; (3) reacting said sulfamidophenacyl halide with an N-benzyl R<SP>4</SP>-substituted amine to produce a compound of the Formula II  wherein R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> and R<SP>4</SP> are as defined above, and (4) hydrogenating the compound of Formula II to cleave the N-benzyl group, reduce the carbonyl group to a carbinol group and produce the compound of Formula I; or if desired, reacting the sulfamidophenacyl halide produced in step (2) with hexamethylenetetramine or an alkali metal phthalimide, hydrolyzing the resultant reaction product to produce the corresponding sulfamidophenacylamine, reducing the latter to convert the carbonyl group to a carbinol group and produce the compound of Formula I where R<SP>4</SP> is hydrogen which may optionally be subjected to reductive alkylation with an alkyl aldehyde or ketone of from 1 to 4 carbon atoms; or, if desired, when a compound of Formula I wherein R<SP>1</SP> or R<SP>2</SP> or R<SP>1</SP> and R<SP>2</SP> are hydrogen is to be produced, acylating the p-aminophenone with an N-tert.-butyl substituted sulfamoyl halide or azide to produce a compound of step (2) wherein R<SP>1</SP> or R<SP>2</SP> is tart.-butyl, then, after carrying out steps (3) and (4), removing the tert.-butyl group by contacting the tert.-butyl sulfamide with trifluroacetic acid; and when a pharmaceutically acceptable salt is desired, producing the latter by treating the compound of Formula I according to a method known per se. The following are the respresentatives of various classes of intermediates prepared in the examples: N - (4 - acetylphenyl) - N<SP>1</SP>,N<SP>1</SP> - dimethylsulphamide by the reaction of dimethylsulphamoyl chloride with p-aminoacetophenone: N - (4 - acetylphenyl) - N<SP>1</SP> - methylsulphamide- N - (4 - acetylphenyl) - N<SP>1</SP> - (4 - tolyl)sulphamide; N - [4 - (bromoacetyl)phenyl]- N<SP>1</SP> - t - butylsulphamide by the side-chain bromination of N - (4 - acetylphenyl) - N<SP>1</SP> - t - butyl sulphamide; N,N - diemthyl - N<SP>1</SP> - (4 - glycylphenyl)sulphamide hydrochloride by treating N-[4-(bromoacetyl)phenyl - N<SP>1</SP>,N<SP>1</SP> - dimethylsulphamide with hexamethylenetetramine and hydrolysing the resultant product; N-[4-(N-benzyl-N-isopropylglycyl)phenyl] - N<SP>1</SP> - t. - butylsulphamide hydrobromide by treating N - [4 - (bromoacetyl)- phenyl] - N<SP>1</SP> - t. - butylsulphamide with benzylisopropylamine; N - (4 - bromoacetyl)- phenylsulphamide by the reaction of N-(4- bromoacetylphenyl) - N<SP>1</SP> - t. - butylsulphamide with F 3 C-COOH. The invention also comprises a process for eliciting in non-human mammals an adrenergic blocking action selective for beta adrenergic receptors in which at least an amount effective to elicit the desired effect of a compound according to the invention is systemically administered to said mammals.