Synthesis and Cytotoxic Activities of Pyrrole[2,3-d]pyridazin-4-one Derivatives.

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I 3,6-diazabiciclo[3.1.1]eptani: una nuova serie di potenti agonisti per i recettori µ degli oppioidi

In questa comunicazione presentiamo la sintesi di una nuova serie di diazabicicloalcani, i 3,6-diazabiciclo[3.1.1]eptani ed i preliminari dati biologici dei composti sintetizzati

LDL-cholesterol control in the primary prevention of cardiovascular diseases. An expert opinion for clinicians and health professionals

Aims: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. Data synthesis: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. Conclusions: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk

3,6-diazabicyclos[3.1.1]heptane derivatives with analgesic activity

The invention relates to compounds of general formula (I), wherein R and R1, different from one another, are: a C2-C8 straight or branched acyl group; and a group of formula (II), wherein B and R2 are as defined in the description. The compounds (I) have higher central analgesic activity than morphine and are substantially free from the side effects of morphine or other central analgesics. The invention further relates to a process for the preparation of the compounds (I)

Oxadiazoles having antiproliferative activity

Oxadiazole derivatives of general formula (1) in which X, Y, R and R2 have the meanings defined in the disclosure. The compounds have antiproliferative activity against a number of human tumors cell lines and can therefore be used for the preparation of antitumor medicaments

Synthesis and cytotoxic activities of pyrrole[2,3-<i>d</i>]pyridazin-4-one derivatives

1-Methyl-2-phenyl (1) and 1,3-dimethyl-2-phenyl (2) -substituted pyrrole[2,3-d]pyridazinones, as well as their tetracyclic analogues 3—6, were synthesized and evaluated in vitro by the National Cancer Institute against 60 human tumor cell lines derived from nine cancer cell types. Biological results showed that the antitumor activities of these compounds were related to the planarity of their ring systems with potency increasing in the order 2&lt;4 5&lt;6&lt;3. Among them, the most potent compound 3 showed significant cell line cytotoxicity, particularly against the renal cancer subpanel [GI50 (µM) 5.07] and displayed significant potency [GI50 (µM) 3.04—4.32] against MOLT-4, SR (leukemia), NCI-H460 (non-small cell lung), HCT-116 (colon), and SF-295 (CNS) cancer cells, respectively

Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors

In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba–i) were synthesized and their affinity and selectivity towards μ-, δ- and κ-receptors were evaluated. The results of the current study revealed a number of compounds (3Bb, 3Bg and 3Bh) having a high affinity for μ (Ki at μ-receptors ranging from 2.7 to 7.9 nM) versus δ (Ki at δ-receptors >2000 nM) and versus κ (Ki at κ-receptors >5000 nM) receptors. Molecular modelling carried out on the pair 3Aa/3Ba and on the 3Bh was consistent with the hypothesis that the two series of compounds 3A and 3B interact with the μ-receptor in very different ways