3160-59-6Relevant articles and documents
Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors
Mousa, Mai H. A.,Ahmed, Nermin S.,Schwedtmann, Kai,Frakolaki, Efseveia,Vassilaki, Niki,Zoidis, Grigoris,Weigand, Jan J.,Abadi, Ashraf H.
, (2021/04/16)
Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.
Synthesis of enantiopure free and N-benzyloxycarbonyl-protected 3-substituted homotaurines from naturally occurring amino acids
Zheng, Yongpeng,Xu, Jiaxi
, p. 5197 - 5206 (2014/12/10)
Enantiopure N-benzyloxycarbonyl-protected and free 3-substituted homotaurines were synthesized from naturally occurring amino acids via N-benzyloxycarbonyl protection, Arndt-Eistert homologation, reduction, esterification with thioacetic acid, and oxidation with performic acid. The current method is a convenient, practical, and salt-free method for the synthesis of enantiopure 3-substituted homotaurine with moderate to good yields.
Assay and inhibition of diacylglycerol lipase activity
Johnston, Meghan,Bhatt, Shachi R.,Sikka, Surina,Mercier, Richard W.,West, Jay M.,Makriyannis, Alexandros,Gatley, S. John,Duclos Jr., Richard I.
scheme or table, p. 4585 - 4592 (2012/08/08)
A series of N-formyl-α-amino acid esters of β-lactone derivatives structurally related to tetrahydrolipstatin (THL) and O-3841 were synthesized that inhibit human and murine diacylglycerol lipase (DAGL) activities. New ether lipid reporter compounds were developed for an in vitro assay to efficiently screen inhibitors of 1,2-diacyl-sn-glycerol hydrolysis and related lipase activities using fluorescence resonance energy transfer (FRET). A standardized thin layer chromatography (TLC) radioassay of diacylglycerol lipase activity utilizing the labeled endogenous substrate [1″- 14C]1-stearoyl-2-arachidonoyl-sn-glycerol with phosphorimaging detection was used to quantify inhibition by following formation of the initial product [1″-14C]2-arachidonoylglycerol and further hydrolysis under the assay conditions to [1-14C]arachidonic acid.
