18931-60-7Relevant articles and documents
Tetrahydropyrimidinones/thiones stabilized by trifluoromethyl-containing β-diketones
Adigun, Rasheed A.,Malan, Frederick P.,Balogun, Mohammed O.,October, Natasha
, (2020)
A library of new hydropyrimidinone/thione compounds was synthesized via the classical Biginelli reaction using hydrated cerium(III) chloride as the catalyst. The presence of a trifluoromethyl or methyl group in the diketone starting material has been established to selectively control the outcome of the Biginelli reaction where one of the two possible pyrimidinone/thione compounds is formed. The results showed that the electronic effects of substituents of the diketone directly affect the product formation. The synthesized compounds were fully characterized using 1H, 13C, and two dimensional NMR (2D NMR) spectroscopy, single crystal X-ray diffractometry, FT-IR, and ESI-HDMS techniques. We also report on the uncommon one-bond correlations which were observed in the HMBC spectra and the interesting long-range heteronuclear coupling of fluorine to hydrogen and carbon.
An Integrated Continuous Flow Micro-Total Ultrafast Process System (μ-TUFPS) for the Synthesis of Celecoxib and Other Cyclooxygenase Inhibitors
Sthalam, Vinay Kumar,Singh, Ajay K.,Pabbaraja, Srihari
supporting information, p. 1892 - 1899 (2019/10/11)
Integrated continuous manufacturing has emerged as a promising device for the rapid manufacturing of active pharmaceutical ingredients (APIs). We herein report a newly designed continuous flow micro-total process system platform for the rapid manufacturing of celecoxib, a selective nonsteroidal anti-inflammatory drug. This approach has been proven generally for the synthesis of several alkyl and aryl substituted pyrazoles. In order to minimize the tedious work-up process of potential reaction intermediates/products, we have developed a continuous flow extraction and separation platform to carry out the entire reaction sequence resulting in a short residence time with good yield. The present process was further extended to gram-scale synthesis of the COX-2-related API, viz. celecoxib, in the continuous flow process.
An SAR study of hydroxy-trifluoromethylpyrazolines as inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader assay
Stevenson, Ralph J.,Azimi, Iman,Flanagan, Jack U.,Inserra, Marco,Vetter, Irina,Monteith, Gregory R.,Denny, William A.
, p. 3406 - 3413 (2018/05/24)
The proteins Orai1 and STIM1 control store-operated Ca2+ entry (SOCE) into cells. SOCE is important for migration, invasion and metastasis of MDA-MB-231 human triple negative breast cancer (TNBC) cells and has been proposed as a target for cancer drug discovery. Two hit compounds from a medium throughput screen, displayed encouraging inhibition of SOCE in MDA-MB-231 cells, as measured by a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Following NMR spectroscopic analysis of these hits and reassignment of their structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes. Structure-activity relationship (SAR) studies showed that small lipophilic substituents at the 2- and 3-positions of the RHS and 2-, 3- and 4-postions of the LHS terminal benzene rings improved activity, resulting in a novel class of potent and selective inhibitors of SOCE.
