10364-94-0Relevant articles and documents
Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes
Asquith, Christopher R. M.,Awad, Dominik,Catta-Preta, Carolina M. C.,Cou?ago, Rafael M.,Drewry, David H.,Eduful, Benjamin J.,Frigo, Daniel E.,Hossain, Mohammad Anwar,Langendorf, Christopher G.,Liang, Yi,Lin, Chenchu,Nay, Kévin,O'Byrne, Sean N.,Oakhill, Jonathan S.,Picado, Alfredo,Pilotte, Joseph R.,Pulliam, Thomas L.,Santiago, André De S.,Scott, John W.,Temme, Louisa,Wells, Carrow I.,Willson, Timothy M.,Zonzini Ramos, Priscila,Zuercher, William J.
, p. 10849 - 10877 (2021)
CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor commonly used to probe CAMKK2 signaling, has limitations. To identify promising scaffolds as starting points for the development of high-quality CAMKK2 chemical probes, we utilized a hinge-binding scaffold hopping strategy to design new CAMKK2 inhibitors. Starting from the potent but promiscuous disubstituted 7-azaindole GSK650934, a total of 32 compounds, composed of single-ring, 5,6-, and 6,6-fused heteroaromatic cores, were synthesized. The compound set was specifically designed to probe interactions with the kinase hinge-binding residues. Compared to GSK650394 and STO-609, 13 compounds displayed similar or better CAMKK2 inhibitory potency in vitro, while compounds 13g and 45 had improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge-binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chemistry programs.
Esterification with aromatic acyl-1,2,4-triazole Catalyzed by weak base at the rate comparable to acyl chloride
Kohsaka, Yasuhiro,Homma, Kazumasa,Sugiyama, Susumu,Kimura, Yoshikazu
, p. 100 - 102 (2018)
Benzoyl-1,2,4-triazole underwent esterification with a primary alcohol in the presence of 4-(N,N-dimethylamino)pyridine (DMAP) catalyst at the rate comparable to benzoyl chloride. The kinetic study concluded that the reaction proceeds in a similar mechanism to carboxylic acid anhydride and is thus sensitive to the steric hindrance of alcohol. As the esterification of benzoyl-1,2,4-triazole did not afford acidic by-product and require an equimolar or more amount of base, it is effective for the protection of acid-sensitive alcohol and polyester synthesis.
Synthesis of N-(protected)aminophthalimides: Application to the synthesis of singly labelled isoniazid
Brosse, Nicolas,Pinto, Maria-Fatima,Jamart-Gregoire, Brigitte
, p. 3685 - 3688 (1998)
The synthesis of a series of N-(protected)aminophthalimides and the removal of their phthaloyl group leading to N-(protected) or N,N-bis(protected)hydrazines is described. As illustrated by the synthesis of monolabelled isoniazid 3b*, this strategy can be utilized for the preparation of monolabelled substituted hydrazines.
Microwave-promoted conversion of heterocyclic amines to corresponding amides under solvent-free conditions
Li, Yanqiu,Wang, Yulu,Wang, Jinye
, p. 251 - 256 (2007)
An array of heterocyclic amides was synthesized efficiently by combining corresponding amines and benzoyl chloride in one-pot under microwave irradiation. The reaction times were shorter, yields were higher. What is more, the regioselectivity was excellent, which made the protocol support us an entry to selective protection of diverse amino groups.
Mild and useful method for n-acylation of amines
Phukan, Kandarpa,Ganguly, Mausumi,Devi, Nirada
, p. 2694 - 2701 (2009)
Iodine is found to promote quantitative N-acylation of primary and secondary amines (aliphatic and aromatic) in a very short time with an equimolar amount of acetyl chloride and benzoyl chloride under solvent-free conditions at room temperature. This catalytic acylation of amines offers an additional useful method for the acetylation using acetyl chloride instead of acetic anhydride and other acetylating agents. This method is also useful in the N-acylation of heterocycles. Mild reaction condition, high selectivity, efficiency, and good yields are some of the major advantages of the procedure.
Synthesis, characterization, and in vitro evaluation of novel ruthenium(II) η6-arene imidazole complexes
Vock, Carsten A.,Scolaro, Claudine,Phillips, Andrew D.,Scopelliti, Rosario,Sava, Gianni,Dyson, Paul J.
, p. 5552 - 5561 (2006)
Ten complexes of general formula [Ru(η6-arene)Cl 2(L)], [Ru(η6-arene)Cl(L)2][X], and [Ru(η6-arene)(L)3][X]2 (η6- arene = benzene, p-cymene; L = imidazole, benzimidazole, N-methylimidazole, N-butylimidazole, N-vinylimidazole, N-benzoylimidazole; X = Cl, BF4, BPh4) have been prepared and characterized by spectroscopy. The structures of five representative compounds have been established in the solid state by single-crystal X-ray diffraction. All the new compounds were assessed by the same in vitro screening assays applied to [imidazole-H][trans-RuCl 4(DMSO)(imidazole)] (NAMI-A) and [Ru(η6-arene)Cl 2(1,3,5-triaza-7-phosphaadamantane)] (RAPTA) compounds. It was found that the new compounds show essentially the same order of cytotoxicity as the RAPTA compounds toward cancer cells. Several of the compounds were selective toward cancer cells in that they were less (or not) cytotoxic toward nontumorigenic cells that are used to model healthy human cells. Thus, two of the compounds, [Ru(η6-p-cymene)Cl(vinylimid)2][Cl] (vinylimid = N-vinylimidazole) and [Ru(η6-benzene)(mimid) 3][BF4]2 (mimid = N-methylimidazole), have been selected for a more detailed in vivo evaluation.
Combined Photoredox and Carbene Catalysis for the Synthesis of γ-Aryloxy Ketones
Fitzpatrick, Keegan P.,Scheidt, Karl A.,Wang, Pengzhi
supporting information, (2021/12/16)
N-heterocyclic carbenes (NHCs) have emerged as catalysts for the construction of C?C bonds in the synthesis of substituted ketones under single-electron processes. Despite these recent reports, there still remains a need to increase the utility and practicality of these reactions by exploring new radical coupling partners. Herein, we report the synthesis of γ-aryloxyketones via combined NHC/photoredox catalysis. In this reaction, an α-aryloxymethyl radical is generated via oxidation of an aryloxymethyl potassium trifluoroborate salt, which is then added into styrene derivatives to provide a stabilized benzylic radical. Subsequent radical-radical coupling reaction with an azolium radical affords the γ-aryloxy ketone products. (Figure presented.).
Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids
Betori, Rick C.,Davies, Anna V.,Fitzpatrick, Keegan P.,Scheidt, Karl A.
supporting information, p. 9143 - 9148 (2020/03/30)
As a key element in the construction of complex organic scaffolds, the formation of C?C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C?C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical–radical coupling was made possible merging N-heterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the late-stage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies.
