4870-65-9Relevant articles and documents
MALIC ENZYME INHIBITORS
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Page/Page column 119, (2021/04/23)
The present invention relates to novel compounds useful as malic enzyme (ME) inhibitors, processes for their preparation and use of these compounds for the therapeutic treatment of disorders mediated by ME such as cancers (e.g. pancreatic ductal adenocarcinoma (PDAC)) in humans.
Novel synthetic method of D/L-phenyl glycine
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Paragraph 0022-0025, (2020/04/22)
The invention relates to a novel synthetic method of D/L-phenyl glycine. An existing synthetic method of D/L-phenylglycine is used for producing D/L-phenyl glycine by using highly toxic raw materials,and the synthetic method is harmful. According to the synthesis method, benzene is used as a solvent and a raw material. The method comprises the following steps: firstly, performing Friedel-Crafts alkylation reaction between benzene and dichloroacetic acid or bromochloroacetic acid under the catalystic function of a catalyst, wherein the reaction temperature of Friedel-Crafts alkylation reactionis 55-60 DEG C, the reaction time is 7h, and after Friedel-Crafts alkylation reaction, a benzene solution of alpha-chlorophenylacetic acid or alpha-bromophenylacetic acid is obtained; separating thereaction product into a water phase by using 20% ammonia water; adding urotropin into the water phase to carry out catalytic reactions at a temperature of 75-80 DEG C for 12 hours, controlling the temperature to be 70-80 DEG C, neutralizing the solution by 30% sulfuric acid until the pH value is equal to 6.5 to obtain a D/L-phenyl glycine water solution, and performing suction filtration to obtaina filter cake, namely D/L-phenyl glycine. Cyanide is not used, production is safe, energy consumption is reduced, and the raw material quality standard of downstream products is met.
A metal-free and mild approach to 1,3,4-oxadiazol-2(3: H)-ones via oxidative C-C bond cleavage using molecular oxygen
Lim, Bumhee,Park, Seunggun,Park, Jae Hyun,Gam, Jongsik,Kim, Sanghee,Yang, Jung Woon,Lee, Jeeyeon
supporting information, p. 2105 - 2113 (2018/03/26)
A mild metal-free approach to 1,3,4-oxadiazol-2(3H)-ones via 1,3,4-oxadiazin-5(6H)-ones is described. This novel transformation, promoted by the electron-withdrawing p-substituents on the phenyl group at the α-carbonyl position, features a tandem reaction consisting of oxidative hydroxylation and C-C bond cleavage using molecular oxygen. The method utilizes K2CO3 in CH3CN without any oxidants, transition metals, or additives, enabling the tunable synthesis of 1,3,4-oxadiazin-5(6H)-ones, 1,3,4-oxadiazol-2(3H)-ones, and α-ketoamides under mild aerobic conditions.
Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer
Xue, Xiaoqian,Zhang, Yan,Wang, Chao,Zhang, Maofeng,Xiang, Qiuping,Wang, Junjian,Wang, Anhui,Li, Chenchang,Zhang, Cheng,Zou, Lingjiao,Wang, Rui,Wu, Shuang,Lu, Yongzhi,Chen, Hongwu,Ding, Ke,Li, Guohui,Xu, Yong
supporting information, p. 542 - 559 (2018/05/24)
The bromodomain and extra-terminal proteins (BET) have emerged as promising therapeutic targets for the treatment of castration-resistant prostate cancer (CRPC). We report the design, synthesis and evaluation of a new series of benzoxazinone-containing 3,5-dimethylisoxazole derivatives as selective BET inhibitors. One of the new compounds, (R)-12 (Y02234), binds to BRD4(1) with a Kd value of 110 nM and blocks bromodomain and acetyl lysine interactions with an IC50 value of 100 nM. It also exhibits selectivity for BET over non-BET bromodomain proteins and demonstrates reasonable anti-proliferation and colony formation inhibition effect in prostate cancer cell lines such as 22Rv1 and C4-2B. The BRD4 inhibitor (R)-12 also significantly suppresses the expression of ERG, Myc and AR target gene PSA at the mRNA level in prostate cancer cells. Treatment with (R)-12 significantly suppresses the tumor growth of prostate cancer (TGI = 70%) in a 22Rv1-derived xenograft model. These data suggest that compound (R)-12 is a promising lead compound for the development of a new class of therapeutics for the treatment of CRPC.
Thiazolidinedione chemical compound preparation method
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Paragraph 0014, (2016/10/07)
The present invention discloses a new thiazolidinedione chemical compound preparation method. The synthetic route is shown in the description wherein R1 and R2 are H, CH3, MeO or t-Bu. The thiazolidinedione chemical compound synthesized by the new method is high in solubility and reactivity. Currently, such method has not yet been reported in the literature. The new method has the following advantages: the method is wide in applicability, short in reaction path, high in reaction efficiency, simple in after-treatment, low in cost, and suitable for industrial production.
Catalytic Asymmetric Conjugate Addition and Sulfenylation of Diarylthiazolidin-2,4-diones
Jiao, Lihui,Bu, Liwei,Ye, Xinyi,Zhao, Xiaowei,Jiang, Zhiyong
, p. 9620 - 9629 (2016/11/02)
This work reports the first application of diarylthiazolidin-2,4-diones as nucleophiles in asymmetric catalysis. By utilizing chiral amino acid-based (thio)urea-tertiary amines as the catalysts, we successively established asymmetric conjugate addition to nitroolefins and sulfenylation to N-(sulfanyl)-succinimides of diarylthiazolidin-2,4-diones. Two series of biologically important 5-aryl-5-substituted thiazolidin-2,4-diones were obtained with high enantio- and diastereoselectivities (up to >99% ee and >19:1 dr). The enantioenriched adducts were found to show satisfactory anticancer activities against three different cancer cell lines using the MTT assay. All of these successes depended on the development of a general and expedient synthetic strategy to provide diverse 5H-thiazolidin-2,4-diones.
Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
supporting information, p. 17869 - 17881 (2015/02/19)
Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
Lipase from Carica papaya latex presents high enantioselectivity toward the resolution of prodrug (R,S)-2-bromophenylacetic acid octyl ester
Rivera, Ivanna,Mateos, Juan Carlos,Marty, Alain,Sandoval, Georgina,Duquesne, Sophie
, p. 5523 - 5526 (2013/09/23)
Besides the well-known papain, lipolytic activity is another interesting enzymatic activity present in latex from Carica papaya. This lipolytic activity is strongly attached to the latex solid phase, resulting in a naturally immobilized biocatalyst. In this work we describe the kinetic resolution of (R,S)-2-bromophenylacetic acid octyl ester by Carica papaya crude latex and two partially purified latex fractions. Several parameters, such as substrate concentration and solvent effects were studied. The best results were obtained using decane as solvent with 50 mM of substrate and 50 mg/mL enzyme/reaction medium; under these conditions, a high enantioselectivity (E >200) was obtained with crude latex. A twofold increase of the initial rate maintaining E >200 was obtained using purified fractions without protease and without esterase. Lipase from Carica papaya latex is the most enantioselective wild-type enzyme ever described for the studied reaction.
Synthesis of enantiomerically enriched-bromonitriles from amino acids
Tka, Najeh,Kraem, Jamil,Hassine, Bechir Ben
, p. 735 - 743 (2013/01/15)
Two methods were investigated for the preparation of six chiral-bromonitriles with different optic purities. The nitrous deamination of amino acids gives-bromoacids, which react with chlorosulfonyl isocyanate followed by triethylamine to afford-bromonitriles with moderate enantiomeric excess. However, the dehydration of corresponding-bromoamids using thionyl chloride gives-bromonitriles with good enantiomeric excess up to 94%. The use of phosphoryl chloride instead of thionyl chloride results in more than 30% racemization as determined by high-performance liquid chromatograpic analysis.
Reactions of α-mercaptocarboxylic acid hydrazides with triethyl orthoesters: Synthesis of 1,3,4-thiadiazin-5(6H)-ones and 1,3,4-oxadiazoles
Kudelko, Agnieszka
experimental part, p. 3616 - 3625 (2012/06/18)
Reactions of α-mercapto-β-phenylpropionic and α-mercaptophenylacetic acid hydrazides with triethyl orthoesters were conducted under N2 in glacial acetic acid and resulted in the formation of two groups of products, derivatives of 1,3,4-thiadiazin-5(6H)-ones and 2-(1-mercaptomethyl)-1,3,4-oxadiazoles. When conducting the same transformations on α-mercaptophenylacetic acid hydrazide in the presence of air, two different products from the 1,3,4-oxadiazole family, the appropriate bis(1,3,4-oxadiazol-2-yl-phenylmethyl) disulfides and 2-benzyl-1,3,4- oxadiazoles, were formed with the liberation of free sulfur. The oxygenated bis(1,3,4-oxadiazol-2-yl-phenylmethyl) disulfides were reduced to the corresponding 2-(1-mercaptomethyl)-1,3,4-oxadiazoles with the use of zinc powder under mild conditions.
