93609-04-2Relevant academic research and scientific papers
Catechol-Substituted L-Chicoric acid analogues as HIV integrase inhibitors
Lee, Jae Yeol,Yoon, Kwon Joong,Lee, Yong Sup
, p. 4331 - 4334 (2007/10/03)
HIV integrase catalyzes the integration of HIV DNA copy into the host cell DNA, which is essential for the production of progeny viruses. L-Chicoric acid and dicaffeoylquinic acids, isolated from plants, are well known potent inhibitors of HIV integrase. The common structural features of these inhibitors are caffeic acid derivatives connected to tartaric acid or quinic acid through ester bonds. In the present study, we have synthesized and tested the inhibitory activities of a new type of HIV IN inhibitors, which has catechol groups in place of caffeoyl groups in the structure of L-chicoric acid. Upon substitution of catechol groups at succinic acid, pyrrole-dicarboxylic acid, maleimide or maleic anhydride, the inhibitory activities (IC50=3.8- 23.6 μM) were retained or remarkably increased when compared to parent compound L-chicoric acid (IC50=13.7 μM).
Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and hiv-1 replication at nontoxic concentrations
Reinke, Ryan A.,King, Peter J.,Victoria, Joseph G.,McDougall, Brenda R.,Ma, Guoxiang,Mao, Yingqun,Reinecke, Manfred G.,Robinson Jr., W. Edward
, p. 3669 - 3683 (2007/10/03)
The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 μM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two biscatechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.
Asymmetric synthesis of a lignan lactone from a meso anhydride
Ward, Robert S.,Pelter, Andrew,Edwards, Mark I.,Gilmore, Jeremy
, p. 12799 - 12814 (2007/10/03)
The synthesis of a meso-2,3-dibenzylbutanedioic acid anhydride is given. Reaction of this with (+)-α-methylbenzylamide proceeds diastereoselectively to give a butanedioic acid monoamide which is converted into an enantiomerically enriched cis-2,3-dibenzyl
Synthesis of 3,4-Bis-dihydro-2(3H)-furanones and 2,3-Bis(m- or p-substituted-benzyl)-butane-1,4-diols.
Neelima,Bhaduri, A. P.
, p. 209 - 215 (2007/10/02)
Stobbe condensation of appropriately substituted aromatic aldehydes with diethyl or dimethyl succinate in the presence of sodium methoxide yields the required starting materials for the synthesis of the title compounds.The diacids (1-4) and half acid-half
