Daunomycin is a new antibiotic isolated from cultures of Streptomyces peucetius. For its physicochemical characteristics it may belong to the group of antibiotics described by Ollis and Sutherland (11). The toxico-pharmacologic studies of Daunomycin administered i.v. to mice and rats indicated an acute LD50 value of 15-20 mg/kg. In the rat daily intravenous administration of 1-1.25 mg/kg for 8-14 days was well tolerated. Daily intravenous injection of 2-2.5 mg/kg for 8 days caused a slight decrease in the number of R.B.C. and W.B.C., but no histological damage was found in duodenal mucosa, testicles and other parenchimas. Daunomycin caused a significant inibition of 10 out of 12 tumors tested. At a daily dose of 1 or 2 mg/kg it had a marked inhibitory effect on ascites tumors (Hepatoma AH 130, Walker carcinoma, Ehrlich carcinoma, sarcoma 180 and O.G.G. myeloma) and remarkably increased the average survival time of the tumor-bearing animals. The antibiotic strongly inhibited also the growth of solid tumors (Ehrlich carcinoma 41.1%, 180 sarcoma 42.2%, Walker carcinoma 66.1%, O.G.G. myeloma 70.8 - 85.2% and MC sarcoma 67.6%). Daunomycin decreased the mitotic index of the Ehrlich ascites tumor and induced mitotic damages of tumor cells.

A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones were synthesized. These bicylic derivatives contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addition, these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features observed are a potent antiamnestic activity after ip administration (minimal effective dose being between 0.3 and 1 mg/kg ip for most compounds), the presence of a bell-shaped dose-response curve and, generally, a reduction of biological activity after po administration. However, the unsubstituted compound (15, dimiracetam) shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the reference drug oxiracetam.

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3-Hydrazinopyridazines substituted in position 6 with a primary amine, secondary amine, or an alkoxy group were synthesized and screened for antihypertensive activity. In general, the 6-dialklamino derivatives are the most active; the (2-hydroxypropyl)methylamino chain provides the best combination of high antihypertensive activity and toxicity.