ChemInform Abstract: A NEW CLASS OF NITROSOUREAS. 4. SYNTHESIS AND ANTITUMOR ACTIVITY OF DISACCHARIDE DERIVATIVES OF 3,3‐DISUBSTITUTED 1‐(2‐CHLOROETHYL)‐1‐NITROSOUREAS

Abstract

Maltose (I) wird in die Chlorethylnitrosoharnstoffe (II) übergeführt.

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…Compound 555 had a much higher therapeutic index and exhibited a higher cytotoxicity against the L1210 when administered by multiple injections, e.g. 1-5 ip/day, than by a single 1 ip/day injection, whereas other clinical nitrosoureas were found 396,447 to result in higher activities and therapeutic ratios on a single injection regimen. Compound 555 had the highest therapeutic ratio against a variety of cancer lines, including L1210 leukemia, Ehrlich carcinoma, sarcoma 180, Lewis lung carcinoma, Yoshida sarcoma, rat ascites hepatomas, and Walker 256 carcinoma, when compared with GANU, ACNU, and CCNU.…”

“…A large series of N3,N3-disubstituted-CENU analogs containing the glucopyranosyl, mannopyranosyl, and galactopyranosyl moieties 440-462 394 (Table 23) and the arabinopyranosyl, xylopyranosyl, and ribopyranosyl moieties 463-483 395 (Table 24) were synthesized as illustrated in Scheme 47a and also reported in several patents. [396][397][398][399] Reaction of the carbohydrates with primary amines yielded the corresponding glycosylamines which, in turn, were converted to the ureas with 2-chloroethyl isocyanate. The products were mixtures of structural isomers which were smoothly transformed to the pure C1-substituted ureas by an acid-catalyzed isomerization.…”

“…443 The gentiobioside derivatives 551 and 552 also exhibited good antileukemic activity (Table 31). 444,445 A large series of N3,N3-disubstituted 1-CENU disaccharide derivatives 553-565 were synthesized 396,397,446 according to Scheme 57a and tested 446 for anticancer activity (Table 31). The formation of a cyclic urethane 566 following the decomposition reaction was proven 446 (Scheme 57b).…”