1914-02-9Relevant academic research and scientific papers
Experimental and Computational Studies of High-Valent Nickel and Palladium Complexes
Camasso, Nicole M.,Canty, Allan J.,Ariafard, Alireza,Sanford, Melanie S.
, p. 4382 - 4393 (2017)
This article describes a detailed comparison of the organometallic chemistry of high-valent nickel and palladium model complexes supported by tris(pyrazolyl)borate and cycloneophyl ligands. The accessibility of the MIII and MIV oxidation states with each metal is investigated through electrochemical and chemical oxidation of the MII precursors. These studies show that the NiII precursor readily undergoes both one- and two-electron oxidations to generate stable NiIII and NiIV products. In contrast, under the conditions examined, the PdII analogue undergoes exclusively two-electron-oxidation reactions to form PdIV. Reactivity studies of isolated NiIV and PdIV complexes show that both participate in C(sp3)-heteroatom coupling reactions and that the reactions at NiIV are approximately 2 orders of magnitude faster than those at PdIV. Experimental and computational mechanistic studies implicate outer-sphere SN2-type pathways for these processes. With most nucleophiles (e.g., phenoxide, acetate, thiophenoxide), the C(sp3)-heteroatom coupling reaction yields a TpMII(σ-aryl) product. However, with azide as the nucleophile, the NiII product of initial C(sp3)-N3 coupling undergoes a subsequent C(sp2)-N insertion reaction. Computations implicate an anionic NiIII-nitrene intermediate in this process and show that the Pd analogue of this species is a much higher energy species. Overall, the combined experimental and computational studies demonstrate remarkable similarities in the chemistry of NiIV and PdIV but an enhanced role for NiIII in enabling reactivity which is distinct from that of palladium.
Synthesis of Indolines by Palladium-Catalyzed Intermolecular Amination of Unactivated C(sp3)-H Bonds
Sun, Xueliang,Wu, Zhuo,Qi, Weixin,Ji, Xiaoming,Cheng, Cang,Zhang, Yanghui
, p. 6508 - 6512 (2019)
A new palladium-catalyzed C(sp3)-H amination reaction has been developed. 1-(tert-Butyl)-2-iodobenzene and its derivatives undergo palladium-catalyzed C-H activation to form palladacycles. The palladacycles are aminated with diaziridinone to form indolines as the final products. The reaction represents a new method for the synthesis of 3,3-disubstituted indolines, which are essential structural motifs in many bioactive compounds and pharmaceutical targets.
4 - Substituted benzene sulfonamide derivative and its preparation method and application
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Paragraph 0153-0156, (2018/04/21)
The present invention discloses a class of new 4-substituted benzene sulfonamide derivatives represented by a formula (I), wherein the 4-substituted benzene sulfonamide derivatives have good antitumor activity, and each group is defined in the specification. The present invention further discloses a preparation method of the derivative, a pharmaceutical composition containing the derivative, and applications of the 4-substituted benzene sulfonamide derivative and the pharmaceutical composition containing the derivative as the antitumor drug. The formula I is defined in the specification.
Iron-Catalyzed Intramolecular Aminations of C(sp3)?H Bonds in Alkylaryl Azides
Alt, Isabel T.,Guttroff, Claudia,Plietker, Bernd
, p. 10582 - 10586 (2017/08/22)
The nucleophilic iron complex Bu4N[Fe(CO)3(NO)] (TBA[Fe]) catalyzes the direct intramolecular amination of unactivated C(sp3)?H bonds in alkylaryl azides, which results in the formation of substituted indoline and tetrahydroquinoline derivatives.
Optimization of a novel series of potent and orally bioavailable GPR119 agonists
Koshizawa, Tomoaki,Morimoto, Toshiharu,Watanabe, Gen,Watanabe, Toshiaki,Yamasaki, Nao,Sawada, Yoshikazu,Fukuda, Tomoaki,Okuda, Ayumu,Shibuya, Kimiyuki,Ohgiya, Tadaaki
, p. 3249 - 3253 (2017/07/07)
We describe the discovery and optimization of a novel series of furo[3,2-d]pyrimidines as G protein-coupled receptor 119 agonists. Agonistic activity of 4 (EC50?=?129?nM) was improved by replacing the intramolecular hydrogen bond between the fluorine atom and the aniline hydrogen in the head moiety with a covalent C-C bond to enhance conformational restriction, which consequently gave a lead compound 12 (EC50?=?53?nM). Optimized compound 26, which was identified by the further optimization of 12, exhibited potent activity (EC50?=?42?nM) with improved clearance in liver microsomes and induced a 33% reduction in blood glucose area under the curve at a dose of 10?mg/kg in an oral glucose tolerance test in C57BL/6N mice.
Substituted ring compound and its method and use thereof
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Paragraph 0474; 0475; 0476; 0477, (2017/08/25)
The invention provides a substituted cyclic compound as well as a use method and application thereof. The compound is a compound as shown in a formula (I) or stereoisomers, stereomers, tautomers, nitric oxides, solvates, metabolites and pharmaceutically acceptable salts or prodrugs of the compound as shown in the formula (I). The invention further provides a medicament composition containing the compound. The compound and the medicament composition are capable of regulating the activity of protein kinase in a biological sample body and are used for protecting, treating or relieving proliferative diseases of patients. The formula (I) is as shown in the specification.
Synthesis of indolines by copper-mediated intramolecular aromatic C-H amination
Takamatsu, Kazutaka,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
, p. 3242 - 3249 (2015/03/30)
A Cu(OAc)2-mediated intramolecular aromatic C-H amination proceeds with the aid of a picolinamide-type bidentate coordination group to deliver the corresponding indolines in good yields. The reaction occurs smoothly even under noble-metal-free conditions, and in some cases the use of an MnO2 terminal oxidant renders the process catalytic in Cu. The mild oxidation aptitude of Cu(OAc)2 and/or MnO2 accommodates the formation of electron-rich thiophene-and indole-fused indoline analogues. The Cu-based system can provide an effective approach to various indolines of potent interest in pharmaceutical and medicinal chemistry.
SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
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Paragraph 0203, (2014/06/24)
The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
Conformationally constrained ortho- Anilino diaryl ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl) -3-(4-(trifluoromethoxy)phenyl)urea, a potent, selective, and bioavailable P2Y1 antagonist
Qiao, Jennifer X.,Wang, Tammy C.,Ruel, Réjean,Thibeault, Carl,L'Heureux, Alexandre,Schumacher, William A.,Spronk, Steven A.,Hiebert, Sheldon,Bouthillier, Gilles,Lloyd, John,Pi, Zulan,Schnur, Dora M.,Abell, Lynn M.,Hua, Ji,Price, Laura A.,Liu, Eddie,Wu, Qimin,Steinbacher, Thomas E.,Bostwick, Jeffrey S.,Chang, Ming,Zheng, Joanna,Gao, Qi,Ma, Baoqing,McDonnell, Patricia A.,Huang, Christine S.,Rehfuss, Robert,Wexler, Ruth R.,Lam, Patrick Y. S.
, p. 9275 - 9295 (2014/01/06)
Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y1 antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y12 antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y1 antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 3l will also be presented. Compound 3l was our first P2Y1 antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.
Rh2(II)-catalyzed intramolecular aliphatic C-H bond amination reactions using aryl azides as the N-atom source
Nguyen, Quyen,Sun, Ke,Driver, Tom G.
supporting information; experimental part, p. 7262 - 7265 (2012/06/16)
Rhodium(II) dicarboxylate complexes were discovered to catalyze the intramolecular amination of unactivated primary, secondary, or tertiary aliphatic C-H bonds using aryl azides as the N-atom precursor. While a strong electron-withdrawing group on the nitrogen atom is typically required to achieve this reaction, we found that both electron-rich and electron-poor aryl azides are efficient sources for the metal nitrene reactive intermediate.
