Synthesis, chemical solvolytic stability and preliminary biological evaluation of (+/-)-N-Boc-CPzI: a pyrazole analog of the left-hand segment of the antitumor agent CC-1065.
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Biomedical subjects
M J Pineda de las Infantas
Publications and source records attributed to M J Pineda de las Infantas.
1H-pyrazolo[4,3-d]pyrimidine-7(6H)-one and 5H-pyrazolo[4,3-d] 1,2,3-triazin-4(3H)-one derivatives. Synthesis and in vitro biological activity at adenosine A1 and A2a receptors.
The affinity of newly synthesized 1H-pyrazolo[4,3-d] pyrimidine-7 (6H)- one (5a-f) and 5H-pyrazolo[4,3-d]1,2,3,-triazin-4(3H)-one (6a-i) derivatives for A1 and A2a adenosine receptors was investigated in rat cerebral membranes. The compounds showed affinities in the micromolar range for both adenosine A1 and A2a receptors. In particular 5d was the most interesting compound and showed some degree of selectivity for the A1 receptor (Ki values being 2 mumol/l; A1/A2a ratio < 0.021). The present study provides useful information for a better understanding of the structure-activity relationships of antagonists at adenosine receptors.
Adenosine↗
Anticancer pyrimidine acyclonucleosides.
Several acyclonucleosides have been synthesized. Series 8 could liberate 5-FU and acrolein selectively in the tumour tissue whilst 9 only discharge 5-FU. The conformational analysis of 8 and 9 has been carried out by means of Molecular Mechanics, using the MM2 force field. It was observed that the open chain linked to the N-1 of the 5-FU moiety mimics the conformational structure of the sugar of desoxyuridine. Biological assays have been carried out in vitro on tumour growth in Ehrlich ascitic cells with the consequent decrease of 35% in the cellular mitosis. IC50 showed values between 3-45 microM for series 8 whilst series 9 were less active than 5-FU. Compared with that of 5-FU the acute and chronic toxicity is considerably decreased.
Animals↗