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A series of derivatives of N-methylformamide (NMF), an experimental antitumor agent, has been prepared, having the general formula R3C(X)NR1R2 where R1 = H, CH3, CD3, CH2CF3, CH2CH2Cl, cyclopropyl, C2H5, CH2OH, CH2OR, CH2N(CH3)2; R2 = H, CH3; R3 = H, CF3, CCl3, CH3, Ph, NHCH3, N(CH3)2; and X = O, S, NH. A further short series of "push-pull" olefins of the general formula R1R2C = CHNR3R4 has been synthesized where R1 = H, CH3 and R2 = H, NO2, CN, CHO, CH3 and R3 = H and R4 = H, CH3, morpholino. These compounds have been tested for activity against the M5076 ovarian sarcoma and the TLX5 lymphoma in mice. NMF was by far the most potent agent of both series with activity against both tumors. Some other compounds showed weak activity, but there is a rigorous structural requirement for activity and most analogues were inactive. Certain members of the series exist as equilibrium mixtures of rotamers about the amide or pro-amide bonds as shown by NMR.

A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on hypoxic V79 cells. The compounds were extremely efficient radiosensitizers of such cells in vitro and were more efficient than known nitroimidazoles of similar type. Their efficiencies as radiosensitizers correlated with their high electron affinity (E7(1] as measured by pulse-radiolysis. However the compounds showed little radiosensitizing activity towards KHT sarcomas in C3H mice. The compounds in this series of nitrofurans were generally more toxic towards hypoxic cells than towards oxic cells in vitro but were less effective upon the basis of a differential effect than were similar nitroimidazoles reported previously.

ChemInform Abstract Eleven title compounds of type (II) are prepared from the respective arylbenzoates (I). Most of the title compounds exist in the enolized form (III) in solution (80-95%); (IIIa) adopts enol structure in the crystal and has space group P21/a, Z=4, but (IIb) as crystal has dione structure, space group P21/c, Z=4.

The 'H n.m.r. spectra of NN-dimethyl-2-nitroethenamine, N-methyl-2-nitroethenamine, and 2nitroethenamine in several solvents have been analysed. In the case of the monomethyl compound, the proportions of different rotamers about the C=C and C-N bonds are found to be solvent dependent. An X-ray crystallographic study of this compound indicates inter-rather than intra-molecular hydrogen bonding in the solid; molecular orbital calculations predict three of the possible four conformers about these bonds to be of similar and much lower energy than the fourth.

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Synthesis and Evaluation of Novel Electrophilic Nitrofurancarboxamides and -carboxylates as Radiosensitizers and BioreductivelyActivated Cytotoxins.-The nitrofurancarboxylic acid (I) is converted into the acid chloride and then coupled with allylamine (IIa) or allyl alcohol (IIb) to produce the amide (IIIa) or the ester (IIIb). These are treated with MCPBA to form the corresponding epoxides (IV). Reaction of (IVa) with the aziridines (V) gives the adducts (VI), whereas the ester (IVb) is cleaved in the reaction with (Vb), yielding the amide (VII). Analogously, the β-(nitrofuranyl)acrylic acid (VIII) is converted into the derivatives (IX). -(NAYLOR, M. A.; STEPHENS, M. A.; COLE, S.; THREADGILL, M. D.; STRATFORD, I. J.; O'NEILL, P.; FIELDEN, E. M.; ADAMS, G. E.; J. Med. Chem. 33 (1990) 9, 2508-2513; Med. Res. Council Radiobiol. Unit, Chilton, Didcot, Oxon OX11 0RD, UK; EN)

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