4068-75-1Relevant articles and documents
Preparation of benz[b]indeno[1,2-e]pyran-11(6H)-ones and benz[b]indeno[1,2-e]thiopyran-11(6H)-one from dilithiated 2-indanone and lithiated methyl salicylates or lithiated methyl thiosalicylate
Townsend, Jessica D.,Williams, Angela R.,Angel, April J.,Finefrock, Anne E.,Beam, Charles F.
, p. 689 - 699 (2000)
Dilithiated 2-indanone was prepared with excess lithium diisopropylamide, and the resulting intermediate was condensed with several lithiated methyl salicylates or lithiated methyl thiosalicylate, which was followed by acid cyclization to benz[b]indeno[1,2-e]pyran-11(6H)-ones 3-9 or benz[b]indeno[1,2-e]thiopyran-11(6H)-one 10, which are rare fused-ring indeno-chromones and a new indeno-thiochromone, respectively.
Optimization of kinetic stabilizers of tetrameric transthyretin: A prospective ligand efficiency-guided approach
Cotrina, Ellen Y.,Blasi, Daniel,Vilà, Marta,Planas, Antoni,Abad-Zapatero, Cele,Centeno, Nuria B.,Quintana, Jordi,Arsequell, Gemma
, (2020/10/23)
In the past few years, attempts have been made to use decision criteria beyond Lipinski's guidelines (Rule of five) to guide drug discovery projects more effectively. Several variables and formulations have been proposed and investigated within the framework of multiparameter optimization methods to guide drug discovery. In this context, the combination of Ligand Efficiency Indices (LEI) has been predominantly used to map and monitor the drug discovery process in a retrospective fashion. Here we provide an example of the use of a novel application of the LEI methodology for prospective lead optimization by using the transthyretin (TTR) fibrillogenesis inhibitor iododiflunisal (IDIF) as example. Using this approach, a number of compounds with theoretical efficiencies higher than the reference compound IDIF were identified. From this group, ten compounds were selected, synthesized and biologically tested. Half of the compounds (5, 6, 7, 8 and 10) showed potencies in terms of IC50 inhibition of TTR aggregation equal or higher than the lead compound. These optimized compounds mapped within the region of more efficient candidates in the corresponding experimental nBEI-NSEI plot, matching their position in the theoretical optimization plane that was used for the prediction. Due to their upstream (North-Eastern) position in the progression lines of NPOL = 3 or 4 of the nBEI-NSEI plot, three of them (5, 6 and 8) are more interesting candidates than iododiflunisal because they have been optimized in the three crucial LEI variables of potency, size and polarity at the same time. This is the first example of the effectiveness of using the combined LEIs within the decision process to validate the application of the LEI formulation for the prospective optimization of lead compounds.
Synthesis, structure and in vitro cytotoxicity testing of some 2-aroylbenzofuran-3-ols
Anh, Dang Thi Tuyet,Cong, Nguyen Tien,Dat, Nguyen Dang,Dung, Pham Duc,Meervelt, Luc Van,Phuong, Tran Hoang,Trang, Huynh Thi Xuan,Trung, Vu Quoc,Tuyen, Nguyen Van
, p. 874 - 882 (2020/09/23)
Five 2-aroyl-5-bromobenzo[b]furan-3-ol compounds (two of which are new) and four new 2-aroyl-5-iodobenzo[b]furan-3-ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and 1H NMR and 13C NMR spectroscopy. Single-crystal X-ray diffraction studies of four compounds, namely, (5-bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)methanone, C15H8BrFO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)methanone, C15H8BrClO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)methanone, C15H8Br2O3, and (4-bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)methanone, C15H8BrIO3, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep-G2, Lu-1 and MCF7. Six compounds show good inhibiting abilities on Hep-G2 cells, with IC50 values of 1.39-8.03?μM.
