Carbocyclic analogues of 5-halocytosine nucleosides.

Carbocyclic analogues of 5-halocytosine nucleosides were prepared by direct halogenation of the carbocyclic analogues of cytidine, 2'-deoxycytidine, 3'-deoxycytidine, or ara-C. The 5-chloro and 5-bromo derivatives of the cytidine (carbodine) and of the 2'-deoxycytidine analogues and the 5-iodo derivatives of all four of the cytosine nucleoside analogues were prepared. All of the C-5-halocytosine nucleosides, as well as the parent C-cytosine nucleosides, were tested against a strain of herpes simplex virus type 1 (HSV-1) that induces thymidine kinase in host cells. Carbodine, 5-bromocarbodine, C-2'-deoxycytidine, C-5-bromo-2'-deoxycytidine, the four C-5-iodocytosine nucleosides, and C-ara-C inhibited replication of this strain of HSV-1 in cultured cells. Most of these compounds were tested also against the type 2 virus (HSV-2) in vitro and were active. The greatest activity observed was exerted by C-5-iodo-2'-deoxycytidine in inhibiting replication of HSV-1 in L929 cells. In tests against these DNA viruses, carbodine, a ribofuranoside analogue that had been shown previously to be highly active against human influenza A virus in vitro, was the most active compound against HSV-2 and one of the most active compounds against HSV-1 in Vero cells. 5-Bromocarbodine was active against influenza virus, but it was less active than carbodine.

Synthesis and properties of some 13-cis- and all-trans-retinamides.

Several 13-cis-retinamides were synthesized from 13-cis-retinoic acid via either 13-cis-retinoyl chloride or 13-cis-1-retinoylimidazole. All-trans-retinoylglycine was prepared from all-trans-retinoyl chloride and ethyl glycinate. Detailed procedures were developed for the preparation of other all-trans-retinamides on a large scale for studies of the chemoprevention of cancer.

Field desorption mass spectra of methotrexate and folic acid analogs.

Field desorption mass spectra of methotrexate and folic acid analogs yield abundant molecular or quasimolecular ions. At emitter currents above the best anode temperature, fragment ions which are useful as further confirmations of structures are observed.

Isolation of cis- and trans-4-methylcyclophosphamide and antitumor evaluation in vivo.

4-Methylcyclophosphamide was synthesized and separated into cis and trans isomers by column chromatography. Isolation of these isomers permitted individual evaluation against murine leukemia L1210 in vivo and assessment of possible differences in antileukemic activity. Results indicate no appreciable difference in activity of the isomers, suggesting essentially equal facility for activation by mouse liver microsomes in vivo.