| 摘要 |
Dimethyl-biguanide imide derivs. of formula (I) and their stereoisomers and salts are new. In (I), R = the residue of a dicarboxylic acid anhydride, esp. a satd. or unsatd. 4-6C hydrocarbon chain opt. substd. by Me, Pr, allyl, etc.; an aromatic (esp. benzene or naphthalene) ring opt. substd by halogen, OH, or aliphatic gps.; a 5-6C nonaromatic (esp. cyclopentane or cyclohexane) ring opt. substd. by OH or aliphatic gps.; or a 5- or 6-membered aromatic or nonaromatic ring contg. a heteroatom, e.g. N or O. USE/ADVANTAGE - (I) are dimethyl-biguanide prodrugs useful for treating diabetes and macro- and microcirculatory disorders, whether associated with diabetes or not, esp. by oral or parenteral admin. at a dialy dose of 0.2-1g. (I) have lower toxicity and higher and longer-lasting activity than dimethyl-biguanide. In an example, a soln. of 0.1 mole cyanoguanidine and 0.1 mole succinic anhydride in DMF was refluxed for 2 hr. and the ppte. filtered. The prod. was mixed with 0.11 mole Me2NH.HCl and 60 ml hexanol, heated at 150 deg.C with azeotropic H2O removal for 2 hr. and worked up to give an 80% yield of (I; R=CH2CH2).HCl, m.pt. 240-245 deg.C. (I; R=CH2CH2) had an ED50 of 35 mg/kg (p.o.) against streptozotocine-induced glycaemia in rats (cf. 45 mg/kg for dimethyl-biguanide).
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