Leslie M. Werbel

2-nitroimidazole derivatives useful as radiosensitizers for hypoxic tumor cells

Certain α-[(2-nitro-1H-imidazol-1-yl)methyl]-aziridinylethanols and the corresponding aziridine-ring opened analogs are useful as radiation sensitizers for X-irradiation therapy of tumors.

Chapter 13 Antiparasitic Agents

Publisher Summary This chapter presents an effective summary that has appeared on the philosophy of a pharmaceutical company toward the involvement with tropical diseases. The discussion includes a review on new experimental antimalarial drugs and a volume on “new trends in malaria chemotherapy;” major forthcoming therapeutic advances for Leishmaniasis disease entity; human and animal Trypanosomiasis as world public health problems has appeared; Trichomoniasis as the metronidazole drug, although having typoxic effect, continues to be used as very likely the best available agent for this infection. The discussion has been made enriched by the discussion on both protozoal diseases and helminth diseases that include filaria, other nematodes, and schistosomiasis. The first clinical reports using praziquantel against schistosomiasis appear promising. The pharmacokinetic behavior was dominated by rapid metabolism. No clinically relevant changes were found for any of the laboratory parameters measured in healthy volunteers given total doses as high as 7.5 mg/kg. Amoebiasis, giardiasis, toxoplasmosis, coccidiosis, and are few more have been focused in the chapter. Ionophorous antibiotics recently have been found effective in poultry and mammals. Lasalocid added to feed in a dose to produce the equivalent of about 3.0 mg/kg has been found effective in controlling clinical coccidiosis in calves. This is supported by a review of a variety of drug types.

SYNTHESIS AND ANTIMALARIAL EFFECTS OF 2‐(3,4‐DICHLOROANILINO)‐7‐(((DIALKYLAMINO)ALKYL)AMINO)‐5‐METHYL‐S‐TRIAZOLO(1,5‐A)PYRIMIDINES(1,2)

3,4-Dichlorophenylisothioeyanate (10) was allowed to react with 2-methy1-2-thiopseudourea to give methyl 4-(3,4-dichlorophenyl)(dithioaltophanimidate (11) (41%), which upon treatment with hydrazine afforded 3-amino-5-(3,4-dichloroanilino)-s-triazole (12) (54-91%). Ring-closure with ethyl acetoacetale in acetic acid afforded 2-(3,4-dichloroanilino)-5-methyl-s-triazolo[ 1,5-α ]-pyrimidin-7-ol (13) (81%). Chlorination with phosphorus oxychloride gave 7-chloro-2-(3,4-dichloroanilino)-5-methyl-s-triazolo[1,5-α ]pyrimidine (14) (98%), which was condensed with various amines to yield the desired 2-(3,4-diehloroanilino)-7-¶[(dialkylamino)alkyl]arnino¶-5-methyl-s-triazolo[ 1,5-α]pyrimidines (6a-d). The structures of the s-triazolo[ 1,5-α ]pyrimidines were based on nmr spectroscopy and ring stability considerations. Several of the amino-s-triazolo[ 1,5-α ]pyrimidines possessed antimalarial activity against P. berghei in mice.