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.
Performance comparison of two cascade reaction models in fluorescence off-on detection of hydrogen sulfide
Saha, Tanmoy,Kand, Dnyaneshwar,Talukdar, Pinaki
, p. 1438 - 1446 (2015)
Comparative studies on the performances of two cascade reaction based fluorescent H2S probes are reported. These probes were also designed to address the solubility issues of existing probes. The Reso-N3 probe favors the H2S mediated azide-to-amine reduction followed by a cyclization to release the resorufin fluorophore. Reso-Br undergoes a bromide-to-thiol nucleophilic substitution followed by a similar cyclization releasing the same fluorophore. Reso-N3 exhibited lower background fluorescence and better H2S sensing behavior in water compared to Reso-Br. Reso-Br underwent hydrolysis in aqueous buffer conditions (pH = 7.4) while, Reso-N3 was quite stable. Reso-N3 displayed high selectivity and sensitivity towards H2S. Live cell imaging of the species by the probe was also established. This journal is
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.
Copper-promoted direct amidation of isoindolinone scaffolds by sodium persulfate
Lai, Huifang,Lin, Jin,Xu, Jiexin,Zha, Daijun
, p. 7621 - 7626 (2021/09/22)
Isoindolinones are ubiquitous structural motifs in natural products and pharmaceuticals. Establishing an efficient method for structural modification of isoindolinones could significantly facilitate new drug development. Herein, we describe copper-promoted direct amidation of isoindolinone scaffolds mediated by sodium persulfate. The method exhibits mild reaction conditions and high site-selectivity, and enables the structural modification of the drug indobufen ester with various amides with yields of 49 to 98%. It is also gram-scalable. Additionally, the reaction mechanism appears to involve a radical and a carbocationic pathway.
Design of Chiral NHC-Carboxylates as Potential Ligands for Pd-Catalyzed Enantioselective C?H Activation
Niggli, Nadja E.,Baudoin, Olivier
, (2021/02/26)
Despite numerous efforts, the synthesis of scalemic carbo- and heterocycles through Pd0-catalyzed C(sp3)?H activation employing chiral ancillary ligands or chiral bases is still limited. Inspired by the recently reported outstanding performance of IBiox-type NHC ligands and bifunctional ligands in similar transformations, a new class of bifunctional NHC-ligands bearing a pendant carboxylate group was designed. A library of 10 imidazolium-carboxylic acids was obtained in five to six steps from enantiopure l-tert-leucinol. In addition, four well-defined Pd(DMBPA)-NHC palladacycles were synthesized in good to excellent yields from the corresponding imidazolium precursors. These complexes were tested in a prototypical C(sp3)?H arylation reaction, and the most active one afforded the indoline product in low yield but significant enantioselectivity. These new bifunctional NHCs could find broader applications in catalytic enantioselective transformations occurring under milder conditions.
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.
Polycyclic pyridone derivative, pharmaceutical composition and application thereof
-
Paragraph 0127; 0135-0136, (2021/05/01)
The invention belongs to the field of medicines, and relates to a polycyclic pyridone derivative, a pharmaceutical composition and application thereof. The polycyclic pyridone derivative is a compound as shown in a formula (I) or a stereoisomer, a tautomer, a nitric oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrugs of the compound as shown in the formula (I). Compared with the existing similar compounds, the compound disclosed by the invention not only can well inhibit the replication of influenza viruses, but also has lower cytotoxicity.
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.
Synthesis and Anti-Influenza Virus Effects of Novel Substituted Polycyclic Pyridone Derivatives Modified from Baloxavir
Chen, Dawei,Gao, Zhenxiong,Hou, Jinqiang,Jiang, Yuyang,Tang, Lin,Wu, Weibin,Yan, Haiyan,Zhang, Cunlong
supporting information, p. 14465 - 14476 (2021/10/12)
In this work, a series of novel substituted polycyclic pyridone derivatives were designed and synthesized as potent anti-influenza agents. The cytopathic effect (CPE) assay and cytotoxicity assay indicated that all of the compounds possessed potent anti-influenza virus activity and relatively low cytotoxicity; some of them inhibited the replication of influenza A virus (IAV) at picomolar concentrations. Further studies revealed that, at a concentration of 3 nM, three compounds (10a, 10d, and 10g) could significantly reduce the M2 RNA amounts and M2 protein expression of IAV and inhibit the activity of RNA-dependent RNA polymerase (RdRp). Among them, (R)-12-(5H-dibenzo[a,d][7]annulen-5-yl)-7-hydroxy-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (10a) was found to be a promising anti-influenza drug candidate with good human liver microsomal stability, as well as with better selectivity index and oral bioavailability than Baloxavir.
Synthesis of Disulfide-Bridged N-Phenyl-N′-(alkyl/aryl/heteroaryl)urea Derivatives and Evaluation of Their Antimicrobial Activities
Dilem Do?an, ?engül,Buran, Sümeyye,G?zde Gündüz, Miyase,?zkul, Ceren,Siva Krishna, Vagolu,Sriram, Dharmarajan
, (2019/11/22)
The discoveryof new antimicrobial agents is extremely needed to overcome multidrug-resistant bacterial and tuberculosis infections. In the present study, eight novel substituted urea derivatives (10a–10h) containing disulfide bond were designed, synthesized and screened for their in vitro antimicrobial activities on standard strains of Gram-positive and Gram-negative bacteria as well as on Mycobacterium tuberculosis. According to the obtained results, antibacterial effects of the compounds were found to be considerably better than their antimycobacterial activities along with their weak cytotoxic effects. Molecular docking studies were performed to gain insights into the antibacterial activity mechanism of the synthesized compounds. The interactions and the orientation of compound 10a (1,1′-((disulfanediylbis(methylene))bis(2,1-phenylene))bis(3-phenylurea)) were found to be highly similar to the original ligand within the binding pocket E. faecalis β-ketoacyl acyl carrier protein synthase III (FabH). Finally, a theoretical study was established to predict the physicochemical properties of the compounds.
