41438-38-4Relevant academic research and scientific papers
HISTONE DEMETHYLASE 5 INHIBITORS AND USES THEREOF
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Paragraph 00355-00356, (2020/03/02)
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the compounds or compositions disclosed herein for treating and/or preventing proliferative diseases, cancers, carcinoma lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, leukemia, sarcoma and/or cardiovascular diseases in a subject in need thereof. In certain embodiments, the sarcoma is Ewing's sarcoma. Provided are methods of inhibiting a histone demethylase in a subject and/or in a cell, tissue, or biological sample. In certain embodiments, the histone demethylase is a KDM. In certain embodiments, the KDM is KDM5. In certain embodiments, the biological sample is a cell. In certain embodiments, the biological sample is a tissue.
Zinc and Cadmium Complexes of Pyridinemethanol Carboxylates: Metal Carboxylate Zwitterions and Metal–Organic Frameworks
Lin, Shi-Xin,Liu, Quan,Liu, Yan,Niu, Ru-Jie,Young, David J.,Zhang, Wen-Hua
, p. 832 - 837 (2020/06/03)
The heterofunctional lactone furo[3,4-b]pyridin-5(7H)-one (L1) undergoes a coordination-induced ring-opening reaction with Zn(NO3)2 ? 6H2O to yield the zwitterionic [Zn(L1′)2(H2O)2] (1, L1′=2-(hydroxymethyl)nicotinate) with an uncoordinated carboxylate. The same reaction with Cd(NO3)2 ? 4H2O provides a two-dimensional (2D) network of [Cd(L1′)2]n (3) with the carboxylates coordinated to cadmium(II) propagating the assembly. The corresponding reactions of Zn(NO3)2 ? 6H2O and Cd(NO3)2 ? 4H2O with 2-(hydroxymethyl)isonicotinic acid (HL2) generated zwitterionic [Zn(L2)2(H2O)2] (2) and a 2D network [Cd(L2)2]n?nDMF (4, DMF=N,N′-dimethylformamide), respectively. Complexes 1–4 are weakly emissive, giving ligand-centered emissions at 409 nm (1), 412/436 nm (2), 404 nm (3), and 412/436 nm (4) in CHCl3 solutions upon excitation at 330 nm. This work points to the potential of using ‘hidden’ functionalities widely found in small organic molecules and natural products for the construction of coordination complexes with new functionality and potential applications.
Selective DIBAL-H Monoreduction of a Diester Using Continuous Flow Chemistry: From Benchtop to Kilo Lab
Uhlig, Nick,Martins, Andrew,Gao, Detian
, p. 2326 - 2335 (2020/06/08)
Herein we report a selective DIBAL-H-mediated reduction of a heterocyclic diester to the corresponding monoaldehyde using continuous flow chemistry. The use of continuous flow enabled operation at lower temperatures and better control of the reaction time, thereby allowing for a significant increase in reaction selectivity and yield compared with batch conditions. The reaction's development as a continuous flow process and its scale-up from laboratory gram scale to multikilogram scale are discussed, including design of experiments studies to probe the optimal reaction window.
Reductive Cyclization of Unactivated Alkyl Chlorides with Tethered Alkenes under Visible-Light Photoredox Catalysis
Claros, Miguel,Ungeheuer, Felix,Franco, Federico,Martin-Diaconescu, Vlad,Casitas, Alicia,Lloret-Fillol, Julio
supporting information, p. 4869 - 4874 (2019/03/17)
The chemical inertness of abundant and commercially available alkyl chlorides precludes their widespread use as reactants in chemical transformations. Presented in this work is a metallaphotoredox methodology to achieve the catalytic intramolecular reductive cyclization of unactivated alkyl chlorides with tethered alkenes. The cleavage of strong C(sp3)?Cl bonds is mediated by a highly nucleophilic low-valent cobalt or nickel intermediate generated by visible-light photoredox reduction employing a copper photosensitizer. The high basicity and multidentate nature of the ligands are key to obtaining efficient metal catalysts for the functionalization of unactivated alkyl chlorides.
PROCESS FOR THE PREPARATION OF 2,4- OR 2,5-PYRIDINEDICARBOXYLIC ACID AND COPOLYMERS DERIVED THEREFROM
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Paragraph 0198-0199, (2018/06/09)
The present invention relates to processes for the formation of pyridinedicarboxylic acid (PDCA), in particular, 2,4-pyridinedicarboxylic acid (2,4-PDCA) and 2,5-pyridinedicarboxylic acid (2,5-PDCA), and mono- and diester derivatives thereof, from 3,4-dihydroxybenzoic acid, via a biocatalytic reaction using, for example, a protocatechuate dioxygenase such as protocatechuate 4,5-dioxygenase or protocatechuate 2,3-dioxygenase, and a nitrogen source. The invention also relates to copolymers that comprise the pyridinedicarboxylic acid monomers and derivatives thereof, processes for the formation of the copolymers and uses for the copolymers.
8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors
Bavetsias, Vassilios,Lanigan, Rachel M.,Ruda, Gian Filippo,Atrash, Butrus,McLaughlin, Mark G.,Tumber, Anthony,Mok, N. Yi,Le Bihan, Yann-Va?,Dempster, Sally,Boxall, Katherine J.,Jeganathan, Fiona,Hatch, Stephanie B.,Savitsky, Pavel,Velupillai, Srikannathasan,Krojer, Tobias,England, Katherine S.,Sejberg, Jimmy,Thai, Ching,Donovan, Adam,Pal, Akos,Scozzafava, Giuseppe,Bennett, James M.,Kawamura, Akane,Johansson, Catrine,Szykowska, Aleksandra,Gileadi, Carina,Burgess-Brown, Nicola A.,Von Delft, Frank,Oppermann, Udo,Walters, Zoe,Shipley, Janet,Raynaud, Florence I.,Westaway, Susan M.,Prinjha, Rab K.,Fedorov, Oleg,Burke, Rosemary,Schofield, Christopher J.,Westwood, Isaac M.,Bountra, Chas,Müller, Susanne,Van Montfort, Rob L. M.,Brennan, Paul E.,Blagg, Julian
supporting information, p. 1388 - 1409 (2016/03/05)
We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay.
MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Paragraph 0090; 0091; 0092, (2016/09/22)
Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with methyl modifying enzymes. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with methyl modifying enzymes.
Investigation of cardiovascular effects of tetrahydro-β-carboline sstr3 antagonists
He, Shuwen,Lai, Zhong,Ye, Zhixiong,Dobbelaar, Peter H.,Shah, Shrenik K.,Truong, Quang,Du, Wu,Guo, Liangqin,Liu, Jian,Jian, Tianying,Qi, Hongbo,Bakshi, Raman K.,Hong, Qingmei,Dellureficio, James,Reibarkh, Mikhail,Samuel, Koppara,Reddy, Vijay B.,Mitelman, Stan,Tong, Sharon X.,Chicchi, Gary G.,Tsao, Kwei-Lan,Trusca, Dorina,Wu, Margaret,Shao, Qing,Trujillo, Maria E.,Fernandez, Guillermo,Nelson, Donald,Bunting, Patricia,Kerr, Janet,Fitzgerald, Patrick,Morissette, Pierre,Volksdorf, Sylvia,Eiermann, George J.,Li, Cai,Zhang, Bei,Howard, Andrew D.,Zhou, Yun-Ping,Nargund, Ravi P.,Hagmann, William K.
supporting information, p. 748 - 753 (2014/08/05)
Antagonism of somatostatin subtype receptor 3 (sstr3) has emerged as a potential treatment of Type 2 diabetes. Unfortunately, the development of our first preclinical candidate, MK-4256, was discontinued due to a dose-dependent QTc (QT interval corrected for heart rate) prolongation observed in a conscious cardiovascular (CV) dog model. As the fate of the entire program rested on resolving this issue, it was imperative to determine whether the observed QTc prolongation was associated with hERG channel (the protein encoded by the human Ether-à-go-go-Related Gene) binding or was mechanism-based as a result of antagonizing sstr3. We investigated a structural series containing carboxylic acids to reduce the putative hERG off-target activity. A key tool compound, 3A, was identified from this SAR effort. As a potent sstr3 antagonist, 3A was shown to reduce glucose excursion in a mouse oGTT assay. Consistent with its minimal hERG activity from in vitro assays, 3A elicited little to no effect in an anesthetized, vagus-intact CV dog model at high plasma drug levels. These results afforded the critical conclusion that sstr3 antagonism is not responsible for the QTc effects and therefore cleared a path for the program to progress.
SUBSTITUTED DICYANOPYRIDINES AND USE THEREOF
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Paragraph 0481-0484, (2013/08/28)
The present application relates to novel substituted dicyanopyridines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prophylaxis of cardiovascular disorders.
Substituent effects on the catalytic activity of bipyrrolidine-based iron complexes
Olivo, Giorgio,Lanzalunga, Osvaldo,Mandolini, Luigi,Di Stefano, Stefano
supporting information, p. 11508 - 11512 (2013/12/04)
The catalytic activity and the selectivity of the new bipyrrolidine-based Fe(II) complexes 2·Fe(OTf)2 and 3·Fe(OTf)2 in the oxidation of a series of alkyl and alkenyl hydrocarbons as well as of an aromatic sulfide with H2O2 were tested and compared with the catalytic efficiency of White's parent complex 1·Fe(OTf)2 in order to evaluate the sensitivity of the reaction to electronic effects.
