116144-68-4Relevant articles and documents
Second Generation of cycloSal-Pronucleotides with Esterase-Cleavable Sites: The "Lock-In"-Concept
Meier, Chris,Ruppel, Manuel F. H.,Vukadinovic, Dalibor,Balzarini, Jan
, p. 89 - 115 (2007/10/03)
A conceptual extension of the cycloSal-pronucleotide approach is presented. The characteristic feature of the new cycloSal-derivatives of the anti-HIV active nucleoside analogue d4T 1 is the incorporation of an enzymatically cleavable carboxylic ester moiety with the intention to trap the triesters inside cells ("lock-in"-concept). CycloSal-triesters bearing different ester groups in the 3-or 5-position of the cycloSal-moiety are described. Surprisingly, only acetyl-and levulinyl esters are cleaved readily in CEM cell extracts while alkyl esters were found to be stable. Nevertheless, in in-vitro anti-HIV assays most of the compounds achieve the thymidine-kinase bypass, thus proving that they act at least as nucleotide delivery systems.
Ester Derivatives of 2,6-Bis(1-pyrrolidinylmethyl)-4-benzamidophenol as Short-Acting Antiarrhythmic Agents. 1
Stout, David M.,Black, Lawrence A.,Barcelon-Yang, Cynthia,Matier, W. L.,Brown, Barry S.,et al.
, p. 1910 - 1913 (2007/10/02)
In an effort to find a replacement for the iv antiarrhythmic drug lidocaine having reduced systemic and central nervous system effects, activity against supraventricular as well as ventricular arrhythmias, and a biological half-life of less than 15 min, derivatives of the orally active class Ic clinical agent 2,6-bis(1-pyrrolidinylmethyl)-4-benzamidophenol, 1 (ACC-9358), were synthesized and tested.Compounds with ester groups attached to the phenyl ring were either weakly active or toxic.Replacement of the formanilide function with alkyl esters afforded compounds with antiarrhythmic activity in the range of 1.When the ester carboxyl was separated from the bis(aminomethyl)phenol by methylene units, very short half-lives were observed in human blood.In general, these compounds also had low lipophilic character.
