110409-93-3

Upstream product

• 4385-35-7 isochroman-3-one 
• 100-52-7 benzaldehyde 
• 1256954-44-5 (Z)-benzyl 2-chloro-3-phenylacrylate 
• 5735-41-1 3H-benzo[c][1,2]oxaborol-1-ol 

Relevant academic research and scientific papers

Comparative characterization of experimental and calculated lipophilicity and anti-tumour activity of isochromanone derivatives

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.

Improved solvent-free synthesis and structure elucidation of (E)- and (Z)-4-(arylmethylene)-3-isochromanones

A series of new 4-(arylmethylene)-3-isochromanones 1-17 has been prepared by base-catalyzed Knoevenagel condensations. Stereochemical and conformational analyses were performed by 1H and 13C NMR methods, and X-ray crystallography was used to complement the configurational assignment for a representative product. The reaction generally yields the (E) isomer, but the isomeric composition of the products was influenced by the aromatic aldehyde and usually governed by the stability of the products. Several aldehydes exclusively afforded the (Z) isomer, due to intramolecular steric/electronic interactions reflected in the increased stability of the product. The condensation performed with ortho-hydroxyarenecarbaldehydes furnished the unexpected 3-arylcoumarins or 3-arylbenzocoumarins. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Pd0-Catalyzed carbonylation of 1,1-dichloro-1-alkenes, a new selective access to Z-α-chloroacrylates

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.

Ortho substituents direct regioselective addition of tributyltin hydride to unsymmetrical diaryl (or heteroaryl) alkynes: An efficient route to stannylated stilbene derivatives

An unprecedented ortho-directing effect (ODE) in diaryl alkynes 1 (R=electron-withdrawing or electron-donating group) promotes regioselective addition of tributyltin hydride to the triple bond and afforded efficiently stannylated unsymmetrical 1,2-diaryl olefins 2. The precise contributions of steric, electronic, and coordinative factors, which control this regioselectivity are highlighted. The results are rationalized in terms of electronic polarization across the alkyne bond, induced by the ortho substituent whatever its electronic nature.

DIRECT ACCESS TO 4-SUBSTITUTED 3-ISOCHROMANONES BY THE pH CONTROLLED ADDITION OF ALDEHYDES

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