150057-97-9Relevant academic research and scientific papers
Ni-Catalyzed Aryl Sulfide Synthesis through an Aryl Exchange Reaction
Isshiki, Ryota,Kurosawa, Miki B.,Muto, Kei,Yamaguchi, Junichiro
, p. 10333 - 10340 (2021/07/21)
A Ni-catalyzed aryl sulfide synthesis through an aryl exchange reaction between aryl sulfides and a variety of aryl electrophiles was developed. By using 2-pyridyl sulfide as a sulfide donor, this reaction achieved the synthesis of aryl sulfides without using odorous and toxic thiols. The use of a Ni/dcypt catalyst capable of cleaving and forming aryl-S bonds was important for the aryl exchange reaction between 2-pyridyl sulfides and aryl electrophiles, which include aromatic esters, arenol derivatives, and aryl halides. Mechanistic studies revealed that Ni/dcypt can simultaneously undergo oxidative additions of aryl sulfides and aromatic esters, followed by ligand exchange between the generated aryl-Ni-SR and aryl-Ni-OAr species to furnish aryl exchanged compounds.
Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities
Wang, Pengxu,Batt, Sarah M.,Wang, Bin,Fu, Lei,Qin, Rongfei,Lu, Yu,Li, Gang,Besra, Gurdyal S.,Huang, Haihong
, p. 6241 - 6261 (2021/05/06)
In this study, we report the design and synthesis of a series of novel thiophene-arylamide compounds derived from the noncovalent decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) inhibitor TCA1 through a structure-based scaffold hopping strategy. Systematic optimization of the two side chains flanking the thiophene core led to new lead compounds bearing a thiophene-arylamide scaffold with potent antimycobacterial activity and low cytotoxicity. Compounds 23j, 24f, 25a, and 25b exhibited potent in vitro activity against both drug-susceptible (minimum inhibitory concentration (MIC) = 0.02-0.12 μg/mL) and drug-resistant (MIC = 0.031-0.24 μg/mL) tuberculosis strains while retaining potent DprE1 inhibition (half maximal inhibitory concentration (IC50) = 0.2-0.9 μg/mL) and good intracellular antimycobacterial activity. In addition, these compounds showed good hepatocyte stability and low inhibition of the human ether-à-go-go related gene (hERG) channel. The representative compound 25a with acceptable pharmacokinetic property demonstrated significant bactericidal activity in an acute mouse model of tuberculosis. Moreover, the molecular docking study of template compound 23j provides new insight into the discovery of novel antitubercular agents targeting DprE1.
Diaryl 2- amide-substituted thiophene imide ester compound as well as preparation method and application thereof (by machine translation)
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Paragraph 0153; 0157; 0160-0161; 0164; 0168; 0171-0172, (2020/02/17)
The invention also discloses a 2 - synthesis method thereof, and an application of the compound as an antibacterial agent, in the phthisis-caused by the bacterium, in particular to the, mycobacterium-induced infectious disease (especially (Tuberculosis,TB), mycobacterium- induced mycobacterium, tuberculosis), and (I) the invention, specifically relates to a pharmaceutical composition containing the compound of the present invention or, a R pharmaceutical composition comprising the compound of the present invention. 1 , R2 , R3 , R4 , R5 As described Y in the present invention. as described in the specification, the present invention is directed, to the preparation of novel compounds, having an anti-mycobacterial activity as potential, new drug (s) for the treatment (TB) or preventative treatment of infectious diseases, consisting of M. tuberculosis, in particular phthisis- caused by tubercular mycobacteria, while being useful in overcoming the problems associated with drug resistance. (by machine translation)
DIPROVOCIMS: A NEW AND POTENT CLASS OF TLR AGONISTS
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Page/Page column 122, (2018/02/28)
A diprovocim compound that corresponds in structure to structural Formula V is disclosed, wherein A, W, Z, R1, R2, R3 and R4 (when present) are defined within. A diprovocim compound has immune-adjuvant properties on human and mouse cells in culture and on in vivo immunization of mice. A composition containing a diprovocim and a method of using a compound are also disclosed. The immunostimulatory activity of a diprovocim compound is similar to that of LPS, to which there is no apparent structural similarity. A contemplated compound bears no structural similarity to either the TLR1/TLR2 lipoprotein agonists nor to any other synthetic TLR agonist, and is remarkably easy to prepare and synthetically modify.
Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists
Morin,Wang, Ying,Jones, Brian T.,Mifune, Yuto,Su, Lijing,Shi, Hexin,Moresco, Eva Marie Y.,Zhang, Hong,Beutler, Bruce,Boger, Dale L.
supporting information, p. 14440 - 14454 (2018/10/24)
A screen conducted with nearly 100000 compounds and a surrogate functional assay for stimulation of an immune response that measured the release of TNF-α from treated human THP-1 myeloid cells differentiated along the macrophage line led to the discovery of the diprovocims. Unique to these efforts and of special interest, the screening leads for this new class of activators of an immune response came from a compound library designed to promote cell-surface receptor dimerization. Subsequent comprehensive structure-activity relationship studies improved the potency 800-fold over that of the screening leads, providing diprovocim-1 and diprovocim-2. The diprovocims act by inducing cell-surface toll-like receptor (TLR)-2 dimerization and activation with TLR1 (TLR1/TLR2 agonist), bear no structural similarity to any known natural or synthetic TLR agonist, and are easy to prepare and synthetically modify, and selected members are active in both human and murine systems. The most potent diprovocim (3, diprovocim-1) elicits full agonist activity at extraordinarily low concentrations (EC50= 110 pM) in human THP-1 cells, being more potent than the naturally derived TLR1/TLR2 agonist Pam3CSK4 or any other known small molecule TLR agonist.
NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
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Page/Page column 80, (2009/10/01)
The present invention relates to piperidine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
High-efficiency aminocarbonylation by introducing CO to a pressurized continuous flow reactor
Csajgi, Csaba,Borcsek, Bernadett,Niesz, Krisztin,Kovcs, Ildik,Szkelyhidi, Zsolt,Bajk, Zoltn,Rge, Lszl,Darvas, Ferenc
supporting information; experimental part, p. 1589 - 1592 (2009/04/07)
Halogenated aryl carboxylic acids were efficiently converted to the corresponding dicarboxylic acid monoamides by a one-step Pd-catalyzed aminocarbonylation in a micro/meso fluidic continuous flow reactor (X-Cube) operated at high pressure and high temperature with CO gas introduction. Reaction parameters (solvent, base, catalyst, pressure, temperature) were rapidly optimized in the reactions, which required less than 2 min. The method gave improved results over comparable batch techniques and is also suited to automated parallel syntheses of compound libraries.
PIPERAZINONE DERIVATIVES USEFUL AS HISTAMINE H3 RECEPTOR ANTAGONISTS AND/OR INVERSE AGONISTS
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Page/Page column 43-44, (2010/11/25)
The invention relates to compounds of formula (I) or salts and solvates thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis, wherein R1 and
Dicarboxylic acid azacycle L-prolyl-pyrrolidine amides as prolyl oligopeptidase inhibitors and three-dimensional quantitative structure-activity relationship of the enzyme-inhibitor interactions
Jarho, Elina M.,Wallén, Erik A. A.,Christiaans, Johannes A. M.,Forsberg, Markus M.,Ven?l?inen, Jarkko I.,M?nnist?, Pekka T.,Gynther, Jukka,Poso, Antti
, p. 4772 - 4782 (2007/10/03)
A series of dicarboxylic acid azacycle L-prolyl-pyrrolidine amides was synthesized, and their inhibitory activity against prolyl oligopeptidase (POP) from porcine brain was tested. Three different azacycles were tested at the position beyond P3 and six different dicarboxylic acids at the P3 position. L-Prolyl-pyrrolidine and L-prolyl-2(S)-cyanopyrrolidine were used at the P2-Pl positions. The IC50 values ranged from 0.39 to 19000 nM. The most potent inhibitor was the 3,3-dimethylglutaric acid azepane L-prolyl-2(S)- cyanopyrrolidine amide. Molecular docking (GOLD) was used to analyze binding interactions between different POP inhibitors of this type and the POP enzyme. The data set consisted of the novel inhibitors, inhibitors published previously by our group, and well-known reference compounds. The alignments were further analyzed using comparative molecular similarity indices analysis. The binding of the inhibitors was consistent at the P1-P3 positions. Beyond the P3 position, two different binding modes were found, one that favors lipophilic structures and one that favors nonhydrophobic structures.
Rational design, synthesis, and structure-activity relationships of novel factor Xa inhibitors: (2-substituted-4-amidinophenyl)pyruvic and -propionic acids
Sagi, Kazuyuki,Nakagawa, Tadakiyo,Yamanashi, Masahiro,Makino, Shingo,Takahashi, Mitsuo,Takayanagi, Masaru,Takenaka, Kaoru,Suzuki, Nobuyasu,Oono, Seiji,Kataoka, Noriyasu,Ishikawa, Kohki,Shima, Sayaka,Fukuda, Yumiko,Kayahara, Takashi,Takehana, Shunji,Shima, Yoichiro,Tashiro, Kazumi,Yamamoto, Hiroshi,Yoshimoto, Ryota,Iwata, Seinosuke,Tsuji, Takashi,Sakurai, Kuniya,Shoji, Masataka
, p. 1845 - 1857 (2007/10/03)
An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to
