615-09-8Relevant academic research and scientific papers
Sulfur-controlled and rhodium-catalyzed formal (3 + 3) transannulation of thioacyl carbenes with alk-2-enals and mechanistic insights
Wu, Qiuyue,Dong, Ziyang,Xu, Jiaxi,Yang, Zhanhui
supporting information, p. 3173 - 3180 (2021/04/21)
A rhodium-catalyzed denitrogenative formal (3 + 3) transannulation of 1,2,3-thiadiazoles with alk-2-enals is achieved, producing 2,3-dihydrothiopyran-4-ones in moderate to excellent yields. An inverse KIE of 0.49 is obtained, suggesting the reversibility of the oxidative addition of thioacyl Rh(i) carbenes to alk-2-enals. The late-stage structural modifications of steroid compounds are realized. Moreover, our studies show that thioacyl carbenes have different reactivities to those of α-oxo and α-imino carbenes, and highlight the importance of heteroatoms in deciding the reactivities of heterovinyl carbenes.
Iridium-Catalyzed Enantioselective and Diastereoselective Hydrogenation of Racemic β’-Keto-β-Amino Esters via Dynamic Kinetic Resolution
He, Jiayin,Huang, An,Ling, Fei,Wang, Shiliang,Wang, Yifan,Wang, Ze,Zhao, Xianghua,Zhong, Weihui
supporting information, p. 4714 - 4719 (2021/09/02)
An iridium/f-diaphos catalytic system for the enantioselective hydrogenation of α-substituted β-ketoesters via dynamic kinetic resolution is reported. The desired anti β’-hydroxy-β-amino esters were obtained in moderate to good yields (60–95%) with 72–99% ees and 91:9 to 99:1 drs. This protocol tolerates various functional groups and could be easily conducted on gram scale with lower catalyst loading (TON up to 9100). (Figure presented.).
Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis
Liu, Hao-Nan,Cao, Hao-Qiang,Cheung, Chi Wai,Ma, Jun-An
supporting information, p. 1396 - 1401 (2020/02/22)
Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.
Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of the Pseudomonas aeruginosa Quorum Sensing Receptor LasR with Nanomolar IC50 Values
Blackwell, Helen E.,Manson, Daniel E.,Nyffeler, Kayleigh E.,O'Reilly, Matthew C.
, (2020/03/04)
Quorum sensing (QS), a bacterial cell-to-cell communication system mediated by small molecules and peptides, has received significant interest as a potential target to block infection. The common pathogen Pseudomonas aeruginosa uses QS to regulate many of its virulence phenotypes at high cell densities, and the LasR QS receptor plays a critical role in this process. Small molecule tools that inhibit LasR activity would serve to illuminate its role in P. aeruginosa virulence, but we currently lack highly potent and selective LasR antagonists, despite considerable research in this area. V-06-018, an abiotic small molecule discovered in a high-throughput screen, represents one of the most potent known LasR antagonists but has seen little study since its initial report. Herein, we report a systematic study of the structure-activity relationships (SARs) that govern LasR antagonism by V-06-018. We synthesized a focused library of V-06-018 derivatives and evaluated the library for bioactivity using a variety of cell-based LasR reporter systems. The SAR trends revealed by these experiments allowed us to design probes with 10-fold greater potency than that of V-06-018 and 100-fold greater potency than other commonly used N-acyl-l-homoserine lactone (AHL)-based LasR antagonists, along with high selectivities for LasR. Biochemical experiments to probe the mechanism of antagonism by V-06-018 and its analogues support these compounds interacting with the native ligand-binding site in LasR and, at least in part, stabilizing an inactive form of the protein. The compounds described herein are the most potent and efficacious antagonists of LasR known and represent robust probes both for characterizing the mechanisms of LuxR-type QS and for chemical biology research in general in the growing QS field.
Two Competitive but Switchable Organocatalytic Cascade Reaction Pathways: The Diversified Synthesis of Chiral Acetal-Containing Bridged Cyclic Compounds
Lv, Xue-Jiao,Chen, Ying-Han,Liu, Yan-Kai
supporting information, p. 190 - 195 (2019/01/11)
The organocatalytic enantioselective synthesis of methanobenzodioxepine derivatives bearing a 6,6,5-bridged ring system is presented. The m-CPBA-triggered in situ α-oxidation of β-oxoesters to provide the required but unstable α-hydroxy-β-dicarbonyl substrates is the key to this three-step sequence, providing the desired cyclic acetals with excellent stereoselectivities containing two bridgehead and one fully substituted stereocenters. It is noteworthy that the absence of m-CPBA furnished the acetal products bearing a 6,6,6-bridged ring system with similar good results from the same starting materials.
Inhibitors of Quorum Sensing Receptor LasR
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Paragraph 0198; 0199, (2019/05/07)
Modulation of quorum sensing in Gram-negative bacteria, particularly strains of Pseudomonas which form biofilms, by compounds including those of formula I and formula II: where: AR is optionally substituted phenyl, cycloalkyl or cycloalkenyl or heterocyclic, and R1 is optionally substituted alkyl, alkenyl, alkoxyalkyl, or alkylthioalkyl or alkyl substituted at the omega position with optionally substituted phenyl, cyclohexyl or cyclohexenyl. In particular compounds inhibit quorum sensing and biofilm formation. Pharmaceutical compositions for treatment of bacterial infections and methods of treatment of such infections are provided
Pyrazole alcohol compound, pharmaceutical composition thereof and application thereof to drugs
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Paragraph 0128; 0143, (2018/10/19)
The invention discloses a 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound, a tautomer thereof, a pharmaceutical composition thereof and application thereof to drugs. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound has double effects of resisting platelet aggregation and protecting nerve cells, and comprises a compound as shown in the formula (I), a tautomer (Ia) thereof, or a stereoisomer, a geometrical isomer, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt or prodrug as shown in the description. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound and the pharmaceutical composition thereof provided by the invention can be used for preparing drugs for prevention and/or treatment and/or auxiliary treatment of cerebral apoplexy, cardiovascular and cerebrovascular diseases, senile dementia and complications thereof caused by thrombosis and excessive free radicals.
Substituted phenyl pyrazolone derivatives and preparation and application (by machine translation)
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Paragraph 0034; 0039; 0040, (2019/01/08)
The present invention provides a substituted phenyl pyrazolone derivatives, in particular to a 2 - phenyl - pyrazoline - 3 - ketone compound and its pharmaceutically acceptable salt, solvate. The substituted acetic acid ethyl ester with sodium hydroxide in aqueous solution in the [...] reflux reaction, then in the palladium-carbon and hydrogen under the action of the hydrogenolysis benzyl, phenyl [...] obtained, with the bromochlorodifluoromethane alkane reaction to obtain the chloro, finally with the secondary amine on the condensation to obtain the target compound. The invention substituted phenyl pyrazoline compounds in vitro exhibits excellent capability of eliminating the free radicals, and have more strongly inhibit H3 receptor activity, exhibits excellent penetration of the blood brain barrier capacity, has a unique dual active, therefore, its for cerebral apoplexy, Alzheimer's disease, Parkinson's disease, progressive neurodegenerative diseases such as frozen sickness treatment has a unique clinical effect. The compound of the invention for treating central system system related disease and inflammatory disease application of the medicament. The formula structure is as follows: (by machine translation)
Bromide-Mediated C-H Bond Functionalization: Intermolecular Annulation of Phenylethanone Derivatives with Alkynes for the Synthesis of 1-Naphthols
Lu, Tao,Jiang, Ya-Ting,Ma, Feng-Ping,Tang, Zi-Jing,Kuang, Liu,Wang, Yu-Xuan,Wang, Bin
supporting information, p. 6344 - 6347 (2017/12/08)
Bromide-mediated intermolecular annulation of phenylethanone derivatives with alkynes has been developed, which allows for the regioselective formation of polysubstituted 1-naphthols. The usage of readily available bromine catalyst, broad substrate scope, and mild conditions make this protocol very practical. Mechanistic investigations reveal that the bromination of phenylethanone derivatives occurs to yield bromo-substituted intermediates, which react in situ with alkynes to furnish the desired 1-naphthols.
2 - (3-cyano-4-alkoxy) phenyl-4-substituted thiazole-5- formic acid class compound, composition and its preparation and use
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Paragraph 0165; 0168; 0169, (2016/10/07)
The invention relates to a 2-(3-cyano-4-alkoxy) phenyl-4-substituted thiazole-5-formic acid compound which has xanthine oxidase inhibitory activity and is shown in a general formula I, a composition and preparation methods thereof. The invention also relates to applications of the compound and the composition thereof to preparation of medicaments for treating and/or preventing hyperuricemia and gout diseases. In the formula I, R2 is substituted or unsubstituted phenyl or a substituted or unsubstituted heteroaromatic radical, R1 is a substitutive aliphatic group of a straight chain or a branched chain, substituted or unsubstituted alicyclic hydrocarbonyl or substituted or unsubstituted aryl alkyl and A is an oxygen atom, a sulfur atom or a nitrogen atom.
