Hypoglycemic cycloalkyl lactamimides

Five-, Six-, and Seven-membered Lactim Ethers. Methods of Synthesis and Chemical Properties. (Review)

“…The hydrochlorides 72 were synthesized from lactim ethers and the hydrochlorides of primary amines 71, mostly of the acyclic series, at 20°C without a solvent [90] or in alcohol [91][92][93][94][95] During the condensation of lactim ethers (as a rule at 20°C) with primary amines of the alkyl aromatic series or their hydrochlorides, in which the phenyl or aryl substituents are separated from the amino group by one or several carbon atoms, a large number of products 74 were obtained (yields 25-90%) [94][95][96][97][98][99][100][101][102][103][104][105][106][107]. These reactions were carried out at 20°C (2-26 days) [94][95][96][97][101][102][103][104][105][106][107] or with boiling in xylene (10 h) [103], ether (16 h), or methanol [99]. The reaction of lactim ethers with aniline derivatives 75 was carried out by heating in xylene (3 h) [108] or at 140-150°C (10 h) [100], and as a result the cyclic amidines 76 were obtained.…”

“…The reaction is carried out with heat and usually with distillation of the alcohol. Thus, the lactim ether 95 (n = 3, R 1 = CH 2 Ph) was obtained with a yield of 82% from caprolactim ether (n = 3, R = Me) and benzyl alcohol (5.5 h, benzene, final temperature 120°C) [94]. In the case of butyrolactim ether (n = 1, R = Me) and octyl alcohol (5 h, benzene, N 2 atmosphere, final temperature 120°C) the lactim ether (95) (n = 1, R 1 = C 8 H 17 ) was synthesized with a yield of 53.6% [5].…”

“…Thus, the reaction of isobutyro-and isovalerolactim methyl ethers with isocyanates 4-R-C 6 H 4 NCO (R = H, Cl, OEt) (20°C, 3-7 days) leads to addition at the NCO group with the formation of lactim ethers containing the substituent CONHC 6 H 4 R-4 at position 3. The yields of such amides (butyrolactam derivatives) amount to 20 (R = OEt) to 43% (R = H), and the yields of the analogous valerolactam derivatives amount to 65-70% [156,157].…”

“…In most cases the products 78 were obtained with yields of 50-82% [97,110] by keeping the reagents at 20°C for seven days without a solvent [97][98][99][100][101][102][103][104][105][106][107][108][109][110][111] or in alcohol [95] or by boiling in methanol (3 h) [110] or xylene (10 h) [100].…”

Effect of Cyclo-Alkyl Lactamimides upon Human Pepsins and Pepsinogens

“…Some naphthyl alkyl lactamimides will inhibit Correspondence: Dr N. B. Roberts, Department of Chemical Pathology, Ashton Street, Liverpool L3 5RT, U.K. (Roberts, Grisar, McKenzie, Claxton & Blohm, 1972) and a number of cyclo-alkyl lactamimides possess hypoglycaemic activity (Grisar, Claxton, Carr & Wiech, 1973). One of the latter [N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydro chloride] inhibited secretion of hydrogen ions in the pylorus-ligated rat stomach in a dosedependent manner with a potency slightly greater than that of the histamine H 2 -receptor antagonist, metiamide (Cheng, Munro, Reavis & Woodward, 1976).…”