Several 5 (or 4)-(3-alkyl-3-methyl-l-triazeno)imidazole-4 (or 5)-carboxamides (111-X) were prepared from 5-diazoimidazole-4-carboxamide and the appropriate N-alkyl methylamine. Most of these derivatives significantly increased the life span of leukemic (L1210) mice. Inhibition of the growth of sarcoma 180, adenocarcinoma 755, and Walker carcinosarcoma 256 was observed, but inhibition of solid tumors was generally accompanied by large, adverse, host-weight changes. Qualitative observations of the sensitivity to light of aqueous alcoholic solutions of the dimethyltriazeno (NSC-4 5 388) and the butylmethyltriazeno derivatives indicate a pronounced variation in stability with the kind of light exposure. EPRESENTATIVES OF BOTH disubstituted-

Retinoids that have two functional groups at the side-chain terminus have been synthesized. The two terminal functional groups are combinations of the carboxyl, carbethoxy, and N-(ethylamino)carbonyl groups. The synthesis route is based on the sodium amide catalyzed condensation of (E,E)-beta-ionylideneacetaldehyde with diethyl isopropylidenemalonate. Ethyl 14-carboxyretinoate (6), the initial bifunctional analogue, undergoes isomerization in unbuffered aqueous ethanol and reaches a state of equilibrium with ethyl 14-carboxy-13-cis-retinoate. Both of the possible amide-esters and amide-acids were obtained. The structures of the isomeric bifunctional analogues were established by studies of nuclear Overhauser effects. The bifunctional analogues induce differentiation of mouse embryonal carcinoma cells, and those analogues that have a free carboxyl group bind to cellular retinoic acid binding protein.

2-Haloethyl and ethyl (methylsulfonyl)methanesulfonates were prepared via sulfene intermediates. 2-Chloroethyl (methylsulfonyl)methanesulfonate is highly active against P388 leukemia in vivo; the majority of leukemic mice treated with this compound at 50 mg/kg per day, qd 1-5, survived more than 30 days and about 37% survived for more than 60 days. 2- Fluoroethyl (methylsulfonyl)methanesulfonate is also highly effective against P388 cells in vivo, but it is more toxic. Other (methylsulfonyl)methanesulfonate esters are more active than the analogous methanesulfonates and chloromethanesulfonates .

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