Purine (1)-deoxy (2,3-O)-alkylidene ribofuranonic acid derivs. - with cardiovascular and metabolic activity

摘要

Ribofuranuronic acid derivs. of formula (I) in the form of stereoisomers with an R- or S-configuration at C (and mixts. thereof), and their tautomers and acid-addn. salts are novel. R1 is H or 1-7C alkyl. R2 is OR8 or NR9R10. R3 is H, 1-7C alkyl, 1-7C alkoxy or opt. substd. phenyl. X is OR6 or NR4R5. R4 and R5 are H, 1-7C opt. substd. alkyl, alkenyl or alkynyl, or 3-7C cycloalkyl, or R4 + R5 is a 2-5C alkylene gp. in which a CH2 gp. can be replaced by a heteroatom such as O, S or NR7; R7 = 1-4C alkyl. R6 is H, 1-7C alkyl, 3-7C cycloalkyl, opt. substd. phenyl, or aralkyl. R8 is 1-7C alkyl. R9 and R10 are 1-7C opt. substd. alkyl or 3-7C cycloalkyl, or R9 + R10 is as defined for R4 + R5. Cpds. (I) have a positive inotropic action without lowering blood pressure, and have a strong and long-lasting coronary dilatory effect. They also have a mesenteric and renal vasodilatory action, accompanied by increased blood sugar and insulin levels and decreased free fatty acid levels. A typical cpd. is beta-D-1-(6-amino-9H-purin-9-yl)-1-deoxy-2,3-0-methoxymethylene-r- ibofuranuronic acid ethylamide. In an example, this is prepd. by reacting beta-D-1-(6-amino-9H-purin-9-yl)-1-deoxyribofuranuronic acid ethylamide with trimethyl orthoformate.