17090-71-0Relevant articles and documents
Small molecule QF84139 ameliorates cardiac hypertrophy via activating the AMPK signaling pathway
Li, Xu-xia,Zhang, Peng,Yang, Yang,Wang, Jing-jing,Zheng, Yan-jun,Tan, Ji-liang,Liu, Shen-yan,Yan, Yong-ming,Zhang, You-yi,Cheng, Yong-xian,Yang, Huang-tian
, p. 588 - 601 (2022)
Cardiac hypertrophy is a common adaptive response to a variety of stimuli, but prolonged hypertrophy leads to heart failure. Hence, discovery of agents treating cardiac hypertrophy is urgently needed. In the present study, we investigated the effects of QF84139, a newly synthesized pyrazine derivative, on cardiac hypertrophy and the underlying mechanisms. In neonatal rat cardiomyocytes (NRCMs), pretreatment with QF84139 (1–10 μM) concentration-dependently inhibited phenylephrine-induced hypertrophic responses characterized by fetal genes reactivation, increased ANP protein level and enlarged cardiomyocytes. In adult male mice, administration of QF84139 (5–90 mg·kg?1·d?1, i.p., for 2 weeks) dose-dependently reversed transverse aortic constriction (TAC)-induced cardiac hypertrophy displayed by cardiomyocyte size, left ventricular mass, heart weights, and reactivation of fetal genes. We further revealed that QF84139 selectively activated the AMPK signaling pathway without affecting the phosphorylation of CaMKIIδ, ERK1/2, AKT, PKCε, and P38 kinases in phenylephrine-treated NRCMs and in the hearts of TAC-treated mice. In NRCMs, QF84139 did not show additive effects with metformin on the AMPK activation, whereas the anti-hypertrophic effect of QF84139 was abolished by an AMPK inhibitor Compound C or knockdown of AMPKα2. In AMPKα2-deficient mice, the anti-hypertrophic effect of QF84139 was also vanished. These results demonstrate that QF84139 attenuates the PE- and TAC-induced cardiac hypertrophy via activating the AMPK signaling. This structurally novel compound would be a promising lead compound for developing effective agents for the treatment of cardiac hypertrophy.
Catalytic Asymmetric Darzens-Type Epoxidation of Diazoesters: Highly Enantioselective Synthesis of Trisubstituted Epoxides
Nam, Dong Guk,Shim, Su Yong,Jeong, Hye-Min,Ryu, Do Hyun
supporting information, p. 22236 - 22240 (2021/09/13)
Highly enantioselective Darzens-type epoxidation of diazoesters with glyoxal derivatives was accomplished using a chiral boron–Lewis acid catalyst, which facilitated asymmetric synthesis of trisubstituted α,β-epoxy esters. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in high yield (up to 99 %) with excellent enantio- and diastereoselectivity (up to >99 % ee and >20:1 dr, respectively). The synthetic potential of this method was illustrated by conversion of the products to various compounds such as epoxy γ-butyrolactone, tertiary β-hydroxy ketone and epoxy diester.
Visible-Light-Promoted Photocatalyst-Free Hydroacylation and Diacylation of Alkenes Tuned by NiCl2·DME
Zhao, Xinxin,Li, Bing,Xia, Wujiong
supporting information, p. 1056 - 1061 (2020/02/15)
Herein, we describe a visible light-promoted hydroacylation strategy that facilitates the preparation of ketones from alkenes and 4-acyl-1,4-dihydropyridines via an acyl radical addition and hydrogen atom transfer pathway under photocatalyst-free conditions. The efficiency was highlighted by wide substrate scope, good to high yields, successful scale-up experiments, and expedient preparation of highly functionalized ketone derivatives. In addition, this protocol allows for the synthesis of 1,4-dicarbonyl compounds through alkene diacylation in the presence of NiCl2·DME.
Visible-Light-Induced Regioselective Dicarbonylation of Indolizines with Oxoaldehydes via Direct C-H Functionalization
Teng, Lili,Liu, Xiang,Guo, Pengfeng,Yu, Yue,Cao, Hua
supporting information, p. 3841 - 3845 (2020/05/08)
A metal-free system for regioselective dehydrogenative cross-couplings between indolizines and oxoaldehydes catalyzed by visible light under mild conditions has been described. As an atom economical and eco-friendly protocol, the reaction proceeds in good yields using inexpensive, readily available visible-light sources and the environmentally friendly oxidant oxygen. Various valuable 1,2-dicarbonyl derivatives attached to an indolizine core were easily accessed by the direct dicarbonylation of the sp2 C-H bond.
Antiproliferative Activity of 2-Aroyland 2-Heteroyl-1,1,3,3-Tetracyanoprop-2-en-1-ides
Kayukov, Ya. S.,Mar’yasov, M. A.,Nasakin, O. E.
, (2020/05/22)
The influence of previously synthesized 2-aroyl-1,1,3,3-tetracyanoprop-2-en-1-ides on the growth of conditionally normal and tumor cells was studied in continuation of a search for new anticancer drugs. Cytotoxicities of the compounds were studied with respect to human tumor cell lines from the ATCC. All compounds were ineffective against melanoma and lung and ovary cancer cell lines and exhibited moderate activity in the other cases. The tested compounds exhibited highly selective effects because they were safe for conditionally normal skin fibroblasts.
Asymmetric Conjugate Addition of α-Cyanoketones to Benzoyl Acrylonitrile Derivatives Using a Diaminomethylenemalononitrile Organocatalyst
Akutsu, Hiroshi,Nakashima, Kosuke,Kanetsuna, Yuta,Kawada, Masahiro,Hirashima, Shin-Ichi,Miura, Tsuyoshi
, p. 3874 - 3880 (2020/10/06)
A diaminomethylenemalononitrile (DMM) organocatalyst was used to efficiently promote asymmetric conjugate addition of various α-cyanoketones to benzoyl acrylonitrile derivatives. The corresponding 1,5-dicarbonyl compounds containing vicinal tertiary and quaternary stereogenic centers are versatile synthetic intermediates and were obtained in good yields and with excellent enantioselectivities (up to 96% ee). The present study describes the first successful examples of asymmetric conjugate addition reactions of α-cyanoketones with benzoyl acrylonitriles. In addition, the DMM organocatalyst can be recovered and reused up to five times without significant loss of either catalytic activity or enantioselectivity.
Stereocontrolled Synthesis of 1,4-Dicarbonyl Compounds by Photochemical Organocatalytic Acyl Radical Addition to Enals
Goti, Giulio,Bieszczad, Bartosz,Vega-Pe?aloza, Alberto,Melchiorre, Paolo
supporting information, p. 1213 - 1217 (2019/01/04)
We report a visible-light-mediated organocatalytic strategy for the enantioselective acyl radical conjugate addition to enals, leading to valuable 1,4-dicarbonyl compounds. The process capitalizes upon the excited-state reactivity of 4-acyl-1,4-dihydropyridines that, upon visible-light absorption, can trigger the generation of acyl radicals. By means of a chiral amine catalyst, iminium ion activation of enals ensures a stereoselective radical trap. We also demonstrate how the combination of this acylation process with a second catalyst-controlled bond-forming event allows to selectively access the full matrix of all possible stereoisomers of the resulting 2,3-substituted 1,4-dicarbonyl products.
Cardiac hypertrophy-resistant drug, and preparation method and use thereof
-
Paragraph 0165; 0176; 0177, (2019/07/04)
The invention provides a cardiac hypertrophy-resistant drug, and a preparation method and a use thereof, and concretely discloses a compound represented by formula A, or a pharmaceutically acceptablesalt, an enantiomer, a diastereomer, a tautomer, a solvate, a polymorph or a prodrug thereof, and a preparation method and a pharmaceutical use of the compound. All groups in the formula A are as defined in the description. The compound has the advantages of good cardiac hypertrophy prevention or treatment effect and good development and application prospects.
Modular Synthesis of Di- A nd Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors
De Toledo, Ian,Grigolo, Thiago A.,Bennett, James M.,Elkins, Jonathan M.,Pilli, Ronaldo A.
, p. 14187 - 14201 (2019/10/16)
A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH-imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted NH-imidazoles (23%-69%, three steps). This approach was also employed in the synthesis of known inhibitor GSK3037619A.
Oxidative C-C Bond Cleavage for the Synthesis of Aryl Carboxylic Acids from Aryl Alkyl Ketones
Xu, Liang,Wang, Shengpeng,Chen, Bajin,Li, Meichao,Hu, Xinquan,Hu, Baoxiang,Jin, Liqun,Sun, Nan,Shen, Zhenlu
supporting information, p. 1505 - 1509 (2018/05/25)
A metal-free and one-pot two-step synthesis of aryl carboxylic acids from aryl alkyl ketones has been achieved. The reactions were performed with iodine as the catalyst, DMSO and TBHP as the oxidants. Under the optimal reaction conditions, a number of aryl alkyl ketones could be converted into their corresponding aryl carboxylic acids in good to excellent yields (up to 94%).
