201929-84-2Relevant academic research and scientific papers
THIENO[3,2-B] PYRROLE[3,2-D]PYRIDAZINONE DERIVATIVES AND THEIR USE AS PKM2 DERIVATIVES FOR THE TREATMENT OF CANCER, OBESITY AND DIABETES RELATED DISORDERS
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Page/Page column 118, (2020/08/28)
Described herein are compounds that regulate pyruvate kinase activity, pharmaceutical compositions and methods of use thereof. These compounds are represented by Formula (I) wherein R2, L1-L2, U1-U7, m, ring A, and Q are as defined herein.
ANTIBACTERIAL COMPOUNDS
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Page/Page column 86-89; 102-103, (2019/11/04)
The present application provides compounds of formula: Methods of using these compounds for killing bacterial growth and treating bacterial infections are also provided.
Synthesis method for preparing 2-substituted indole derivative
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Paragraph 0127-0130, (2019/05/28)
The invention relates to a synthesis method for preparing a 2-substituted indole derivative. The method includes the following steps: mixing aromatic amine compounds (I), ketone compounds (II) and a drying agent in an organic solvent; adding a palladium catalyst; and reacting in an aerobic weak acid environment to prepare the indole compounds (III). (I), (II) and (III) are as shown in the specification, wherein R1 is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, hydroxyl, substituted or unsubstituted amino, substituted or unsubstituted phenyl, pyridyl and heterocyclic aryl; (I) can be pyridylamine, pyrimidylamine, pyridazinam or pyrazinamide which may further be substituted or unsubstituted; and the substituents are selected fromone or more C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, hydroxyl, amino; and R2 is selected from C1-C6 alkyl, formate groups or C1-C6 alkylamide groups.
Carboxylic Acid-Promoted Single-Step Indole Construction from Simple Anilines and Ketones via Aerobic Cross-Dehydrogenative Coupling
Ren, Long,Nan, Guanglei,Wang, Yongcheng,Xiao, Zhiyan
, p. 14472 - 14488 (2018/11/23)
The cross-dehydrogenative coupling (CDC) reaction is an efficient strategy for indole synthesis. However, most CDC methods require special substrates, and the presence of inherent groups limits the versatility for further transformation. A carboxylic acid-promoted aerobic catalytic system is developed herein for a single-step synthesis of indoles from simple anilines and ketones. This versatile system is featured by the broad substrate scope and the use of ambient oxygen as an oxidant and is convenient and economical for both laboratory and industry applications. The existence of the labile hydrogen at C-3 and the highly transformable carbonyl at C-2 makes the indoles versatile building blocks for organic synthesis in different contexts. Computational studies based on the density functional theory (DFT) suggest that the rate-determining step is carboxylic acid-assisted condensation of the substrates, rather than the functionalization of aryl C-H. Accordingly, a pathway via imine intermediates is deemed to be the preferred mechanism. In contrast to the general deduction, the in situ formed imine, instead of its enamine isomer, is believed to be involved in the first ligand exchange and later carbopalladation of the α-Me, which shed new light on this indolization mechanism.
Cu nanoparticles immobilized on montmorillonite by biquaternary ammonium salts: a highly active and stable heterogeneous catalyst for cascade sequence to indole-2-carboxylic esters
Lang, Wencheng,Yang, Qin,Song, Xueping,Yin, Mengyun,Zhou, Limei
, p. 13754 - 13759 (2017/03/11)
Copper nanoparticles immobilized on montmorillonite (MMT) by biquaternary ammonium salts (N1,N6-dibenzyl-N1,N1,N6,N6-tetramethylheptane-1,6-diaminium bromide, Q) were prepared by cation-exchange and impregnation-reduction and designated Cu-Q-MMT. The material was extensively characterized by various characterization techniques such as FTIR, XRD, XPS, SEM, TEM, and N2 adsorption-desorption. The Cu-Q-MMT could be used as a highly active heterogeneous catalyst for cascade sequence to indole-2-carboxylic esters from ortho-bromobenzaldehydes with ethyl acetamidoacetate. Even for inactive chlorobenzaldehydes, a good yield could be obtained. In addition, the catalyst can be reused six times without any significant loss of activity. The high activity and stability of the Cu-Q-MMT catalyst is mainly attributed to the excellent synergistic effects of biquaternary ammonium salts, Cu nanoparticles and the nanospace structure of MMT.
Synthesis of Indole-2-carboxylate Derivatives via Palladium-Catalyzed Aerobic Amination of Aryl C-H Bonds
Clagg, Kyle,Hou, Haiyun,Weinstein, Adam B.,Russell, David,Stahl, Shannon S.,Koenig, Stefan G.
, p. 3586 - 3589 (2016/08/16)
A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from 2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron-poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures.
Substituted Indoles as Selective Protease Activated Receptor 4 (PAR-4) Antagonists
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Paragraph 0237, (2016/04/19)
Embodiments of the invention include substituted indole compounds and compositions thereof to inhibit protease activated receptor-4. Also described are methods of preparation of compositions and methods for treating diseases related to thrombotic disorders by administration of the composition.
Development of a series of (1-benzyl-3-(6-methoxypyrimidin-3-yl)-5-(trifluoromethoxy)-1h-indol-2-yl)methanols as selective protease activated receptor 4 (PAR4) antagonists with in vivo utility and activity against γ-thrombin
Temple, Kayla J.,Duvernay, Matthew T.,Young, Summer E.,Wen, Wandong,Wu, Wenjun,Maeng, Jae G.,Blobaum, Anna L.,Stauffer, Shaun R.,Hamm, Heidi E.,Lindsley, Craig W.
supporting information, p. 7690 - 7695 (2016/09/04)
Here, we describe the development of a series of highly selective PAR4 antagonists with nanomolar potency and selectivity versus PARI, derived from the indole-based 3. Of these, 9j (PAR4 IC50 = 445 nM, PARI response IC50 > 30 μM) and lOh (PAR4 IC50 = 179 nM, PARI response IC50 > 30 μM) maintained an overall favorable in vitro DMPK profile, encouraging rat/mouse in vivo pharmacokinetics (PK) and activity against γ-thrombin.
A ligand-free, copper-catalyzed cascade sequence to indole-2-carboxylic esters
Koenig, Stefan G.,Dankwardt, John W.,Liu, Yanbing,Zhao, Hang,Singh, Surendra P.
supporting information; experimental part, p. 6549 - 6551 (2011/02/24)
A variety of indole-2-carboxylic esters are accessible in yields up to 61% through a ligand-free, coppercatalyzed reaction of a series of commercially available 2-halo aryl aldehydes with benign glycine amidoesters, including the common reagent ethyl acetamidoacetate. This one-pot, three-reaction format allows ready entry to the desired heterocycles from starting substrates in the reactivity order of iodo > bromo ≥ chloro substituents. An assortment of functional groups is tolerated, adding to the generality of this methodology.
Assembly of indole-2-carboxylic acid esters through a ligand-free copper-catalysed cascade process
Cai, Qian,Li, Zhengqiu,Wei, Jiajia,Ha, Chengyong,Pei, Duanqing,Ding, Ke
supporting information; experimental part, p. 7581 - 7583 (2010/04/30)
A straightforward synthesis of indole-2-carboxylic esters was developed through a ligand-free copper-catalysed condensation/coupling/deformylation cascade process from 2-halo aryl aldehydes or ketones with ethyl isocyanoacetate. The reactions proceeded we
