2417-73-4Relevant articles and documents
REGIOCHEMICALLY CONTROLLED SYNTHESES OF 3-HYDROXYNAPHTO CYCLOBUTENE BY VICINAL DIESTER DIANION CONDENSATION.
Noire, Paul D.,Franck, Richard W.
, p. 1031 - 1034 (1982)
Utilisation of the dianion derived from dimethyl trans-1,2-cyclobutane dicarboxylate allows for the rapid construction of an unsymmetric naphto cyclobutene by two different routes.
Extension of the polyanionic cosalane pharmacophore as a strategy for increasing anti-HIV potency
Cushman, Mark,Insaf, Shabana,Paul, Gitendra,Ruell, Jeffrey A.,De Clercq, Erik,Schols, Dominique,Pannecouque, Christophe,Witvrouw, Myriam,Schaeffer, Catherine A.,Turpin, Jim A.,Williamson, Karen,Rice, William G.
, p. 1767 - 1777 (1999)
The anti-HIV agent cosalane inhibits both the binding of gp120 to CD4 as well as an undefined postattachment event prior to reverse transcription. Several cosalane analogues having an extended polyanionic 'pharmacophore' were designed based on a hypothetical model of the binding of cosalane to CD4. The analogues were synthesized, and a number of them displayed anti-HIV activity. One of the new analogues was found to possess enhanced potency as an anti-HIV agent relative to cosalane itself. Although the new analogues inhibited both HIV-1 and HIV-2, they were more potent as inhibitors of HIV-1 than HIV-2. Mechanism of action studies indicated that the most potent of the new analogues inhibited fusion of the viral envelope with the cell membrane at lower concentrations than it inhibited attachment, suggesting inhibition of fusion as the primary mechanism of action.
One-pot method to construct isoindolinones and its application to the synthesis of DWP205109 and intermediate of Lenalidomide
Liu, Jinbiao,Lu, Bowei,Lu, Junrui,Wang, Hongbo,Xie, Zhiqiang,Zhong, Kaikai
supporting information, (2021/06/07)
Herein a practical and efficient system for concise synthesis of isoindolinones is described by using substituted methyl 2-(halomethyl)benzoates and substituted amines. Structurally various methyl 2-(halomethyl)benzoates and amines were transformed into isoindolinones 80–99% yield and purity in catalyst-free and solvent-free conditions. The method has a wide substrate scope. The synthetic utility of the one-pot reaction was demonstrated by the concise syntheses of Lenalidomide intermediate and DWP205190.
Discovery of novel ketoxime ether derivatives with potent FXR agonistic activity, oral effectiveness and high liver/blood ratio
Gu, Yipei,Leng, Ying,Ning, Mengmeng,Shen, Jianhua,Tang, Xuehang,Yan, Hongyi,Ye, Yangliang
, (2021/07/16)
The farnesoid X receptor (FXR) is a promising therapeutic target for nonalcoholic steatohepatitis (NASH) and other bile acid related diseases because it plays a critical role in fibrosis, inflammation and bile acid homeostasis. Obeticholic acid (OCA), a FXR agonist which was synthesized from chenodeoxycholic acid, showed desirable curative effects in clinical trials. However, the pruritus which was the main side effect of OCA limited its further applications in NASH. Although pruritus was also observed in the clinical trials of non-steroidal FXR agonists, the proportion of patients with pruritus was much smaller than that of OCA. Thus, we decided to develop non-steroidal FXR agonists and discovered a series of novel FXR agonists which were synthesized from GW4064 by replacing the stilbene group with ketoxime ether. Encouragingly, in the following biological tests, our target compounds 13j and 13z not only showed potent FXR agonistic activities in vitro, but also effectively promoted the expression of target genes in vivo. More importantly, in the pharmacokinetic experiments, compounds 13j and 13z displayed high liver/blood ratio characteristics which were helpful to reduce the potential side effects which were caused by prolonged systemic activation of FXR. In summary, our compounds were good choices for the development of non-steroidal FXR agonists and were deserved further investigation.
