110409-93-3Relevant articles and documents
Comparative characterization of experimental and calculated lipophilicity and anti-tumour activity of isochromanone derivatives
Huszar,Varga,Horvath,Lorand,Agocs,Idei,Mandl,Vantus,Keri
, p. 321 - 333 (2010)
Compound lipophilicity connected to ADME(T)a has great importance in drug development and it has to be evaluated by the generally used drug developmental process. In addition to the importance of lipophilicity in ADMET, recently it has been reported that lipophilicity of small molecules correlates with their antiproliferative activity because of certain specific hydrophobic and lipophilic interactions. Due to the complexity of ADME(T) parameters an efficient and fast method is needed to characterize the many promising candidate lead molecules as a preselection in order not to be rejected from the latter phase of drug development. In the present paper we provide an overview of the importance of lipophilicity of drug candidates for biological action and for ADME(T) and describe a novel approach for drug-likeness characterization of a molecular library using correlation study between lipophilicity and biological activity. Lipophilicity and molecular characteristics have been measured, predicted and optimized for a diverse library from which the best members have been selected to describe their biological, chemical and drug-likeness properties. Molecules were selected from the family of α,β-unsaturated ketones and thorough HPLC characterization for lipophilicity and morphological, antiproliferative and flow cytometric studies were carried out on them. Based on the results 17 member isochromanone library including E and Z geometric isomers were selected for further characterization. In this focused library linear correlation has been found between the calculated and measured lipophilicity and significant parabolic correlation was found between the antiproliferative effect and lipophilicity. Using our efficient and fast method, from a diverse library, we identified an outstandingly effective inhibitor of A431 tumour cell growth via a PARPa cleavage dependent apoptosis. In summary the optimized HPLC analyses of lipophilicity combined with the cell-culture assay, introduced above, resulted in the determination of an optimal lipophilicity range. This optimized lipophilicity range should be used in designing novel antiproliferative compounds.
Pd0-Catalyzed carbonylation of 1,1-dichloro-1-alkenes, a new selective access to Z-α-chloroacrylates
Arthuis, Martin,Lecup, Anne,Roulland, Emmanuel
supporting information; experimental part, p. 7810 - 7812 (2010/11/18)
A novel and fully chemo- and stereoselective three component strategy leading to Z-α-chloroacrylates by a Pd0-catalyzed reaction of CO (1 atm) with 1,1-dichloro-1-alkenes and various alcohols is disclosed. This catalytic approach compares favourably with the Wittig type strategies as α-chloroacrylates of pure Z configuration are obtained in high yield. The Royal Society of Chemistry.
DIRECT ACCESS TO 4-SUBSTITUTED 3-ISOCHROMANONES BY THE pH CONTROLLED ADDITION OF ALDEHYDES
Barbier, Michel
, p. 421 - 425 (2007/10/02)
Aldehydes condense at position 4 of 3-isochromanone in the presence of a base, in competition with the ring opening of the lactone.By control of the pH, the new syn and anti 4-ethyl-idene and benzylidene derivatives are obtained with yields of 30 and 28pe
