GB1425710A - 1-phenothiazine-alkylene-4-acylamino piperidines - Google Patents

Abstract

1425710 Piperidine and tetrahydropyridine derivatives JOHN WYETH & BRO Ltd 10 Dec 1973 [21 Dec 1972 25 Aug 1973] 59140/72 and 40388/73 Addition to 1345872 Heading C2C Novel compounds of Formula I: in which A=C 1-6 alkylene, mono- or di-keto- C 1-6 alkylene or hydroxy-C 1-6 alkylene, each of R<SP>1</SP> and R<SP>2</SP> = H, halogen, C 1-6 alkyl, trihalo-C 1-6 alkyl, OH, alkoxy, NO 2 , amino or protected amino, R<SP>3</SP>=H or -COR<SP>3</SP>, where R<SP>3</SP> = substituted or unsubstituted phenyl, 5-7 ring- membered cycloalkyl or C 1-6 alkyl, and the broken line denotes an optional double bond, and addition salts thereof, are prepared by (a) reaction of a compound of Formula II: with a compound of Formula III: in which Hal=halogen, or (b) reaction of a compound of Formula IV: with a compound of Formula V: in which Y is halogen atom or another replaceable atom or group, or (c) when R<SP>3</SP>=acyl, acylation of compounds I in which R<SP>3</SP>=H, or (d) Mannich reaction with or with subsequent hydrogenation, or (e) when R<SP>3</SP> = H, hydrolysis of corresponding compounds containing a protected amino group, or (f) when A=alkylene, reaction of an appropriate N-hydroxyalkylphenothiazine with a compound of Formula IV. 1 - (Chloroalkyl) - 4 - benzamidopiperidines are prepared by chlorination of corresponding hydroxy compounds. 1 - (3 - Hydroxypropyl) - 4 - benzamidopiperidine is prepared by reaction of 4-benzamidopiperidine with 3-chloropropan-1-ol. Pharmaceutical compositions having hypotensive and/or anti-hypertensive and/or antihistamine activity, comprise a compound I (especially in which R<SP>3</SP> = COR, where R =phenyl or cycloalkyl) or an acid addition salt thereof, together with a pharmaceutical carrier.