Optimization and kinetic model of condensation of a secondary amine with a uracil derivative in the synthesis of 2-[(1-carbethoxy-4-piperidinyl) (methyl)amino]-1H-pyrimidin-4-one.

A series of experiments was performed in order to determine the reaction conditions of 2-(methylsulfanyl)pyrimidin-4(3H)-one [U] with 4-(methylamino)piperidine [A] affording 2-[(1-carbethoxy-4-piperidinyl)(methyl)amino]-1H-pyrimidin-4-one [P] in a high yield (80%) (Scheme 1). Two theoretical approaches i.e.

Toxicity and antineoplastic effect of (24R)-1,24-dihydroxyvitamin D3 (PRI-2191).

Many efforts have been made to obtain active and less toxic Vitamin D analogs for new clinical applications. The results of previous studies demonstrated the efficacy and safety of topical treatment of psoriasis with one of these analogs, 1,24-dihydroxyvitamin D(3), tacalcitol (1,24-(OH)(2)D(3)). In the present study, we evaluated the toxicity and antitumor effect of this analog.

Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D(2). (24E)-(1S)-24-Dehydro-24a-homo-1,25-dihydroxyergocalciferol and congeners.

A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D(2) and D(3). The analogs were obtained by the Julia olefination of C(22)-vitamin D sulfone 11 with side-chain aldehyde 15.

Potentiation of the antiproliferative effect in vitro of doxorubicin, cisplatin and genistein by new analogues of vitamin D.

Numerous vitamin D3 analogues have been synthesised in recent years in order to obtain compounds with a favourable biological and therapeutic (antipsoriatic and/or antitumour) activity. Our results showed that pre-treatment for 72 hours of HL-60 human promyelocytic leukaemia cells with calcitriol or its new analogues significantly potentiated their sensitivity to the antiproliferative effect in vitro of cisplatin, doxorubicin or genistein. Moreover, for all cytotoxic agents tested a synergistic antiproliferative effect was observed.