The Synthesis and Evaluation of Antihypertensive 4-(-Guanidinoethyl)-17-methyl-4-aza-5-androstan-17-ol

[摘要] The intermediate, 17¥á-methyl-4-aza-5¥á-androstan-17¥â-ol(¥¸) required for the synthesis of 4-(¥â-guanidinoethyl)-17¥á-methyl-4-aza-5¥á-androstan-17¥â-ol(V) was obtained through a reaction of 17¥á-methyl-3,5-seco-4-norandrostan-17¥â-ol-5-on-3-oic acid(¥µ) with ammonium hydroxide followed by two reductions(platinum dioxide with hydrogen and lithium aluminium hydride). Condensation of ¥¸ with chloroacetonitrile under anhydrous condition, followed by reduction of the nitrile with lithium aluminium hydride gave 4-(¥â-aminoethyl)-17¥á-methyl-4-aza-5¥á-androstan-17¥â-ol(¥¹¥°). The reaction of ¥¹¥° with 2-methyl-2-thiopseudourea or 3,5-dimethylpyrazole-1-carboxamidine, or cyanamide provided the title compound, V. Relaxation of the nictitating membrane, in the absence of mydriasis, is considered to be evidence of adrenergic neurone blockade. Thus the test compound(V) resembles that of the classical adrenergic neurone blocking agents.

[学科分类] 化学（综合）