GB1090276A - Yohimbane derivatives - Google Patents

Abstract

Novel yohimbanes of the formula <FORM:1090276/C2/1> wherein -C16-C17-C18- is the divalent radical <FORM:1090276/C2/2> (where R is C1- 6 alkyl or phenyl which may be substituted; R1 is C1- 6 alkyl or phenyl which may be substituted; R1 is H, C1- 6 alkyl or phenyl which may be substituted; and R2 is H, OH, NH2, C1- 6S alkyl, or phenyl which may be substituted) and tautomers thereof, and their acid-addition salts are prepared (1) for the yohimbano [17,18] isoxazoles, by treating an 18-acylyohimban-17-one with hydroxylamine, a mixture of 31- and 51-substituted isomers being formed; (2) for the yohimbano [17,18] pyrazoles, by treating an 18-acyl-yohimbano-17-one with hydrazine; (3) for the yohimbano-[17,18] pyrimidines containing (a) no pyrimidine ring substituents, by treating 18-aminomethylene - yohimban - 17 - one with formamide; (b) a 21-amino-substituent, by treating 18-hydroxymethylene - yohimban - 17 - one, or, when, R1 is other than H, an 18-acylyohimban-17-one, with guanidine, e.g. as the carbonate; (c) a 21-alkylthio-substituent, by treating the same starting materials with a 2-alkyl-2-thiopseudourea; (d) a 21-hydroxy-substituent, by hydrolysis of the products of (c); and (e) a 21-phenyl substituent, by treating the same starting materials with a benzamidine. 18-Acylyohimban-17-ones are prepared from enamines of yohimban-17-one, e.g. the pyrrolidine enamine (prepared from the free 17-one and secondary amines) and appropriate acid halides. The novel yohimbanes, which are hypotensive agents, C.N.S. depressants and tranquillizers, may be made up into pharmaceutical compositions for oral or parenteral administration.