17649-31-9Relevant academic research and scientific papers
Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer
Bantzi, Marina,Augsburger, Fiona,Loup, Jérémie,Berset, Yan,Vasilakaki, Sofia,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Szabo, Csaba,Bochet, Christian G.
, p. 6221 - 6240 (2021/05/06)
The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST's active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.
Reaction of 6-Methyl-2-Thiouracil and 6-Phenyl-2-Thiouracil with Chloro-β-Dicarbonyl and Bromo-β-Dicarbonyl Compounds and Their Nitrile Analogs
Yavolovskii,Ivanov, Yu. E.,Fonari,Croitor,Grishchuk,Ivanova, R. Yu.,Kamalov
, p. 2030 - 2035 (2016/11/24)
Derivatives of 2-methylidene-1,3-dihydropyrimidin-4-ones 2a, 2b, 2c, 2d, 2e, 2f, 2g were synthesized by interaction of 6-methyl-2-thiouracil and 6-phenyl-2-thiouracil 1a, 1b with some activated halogenides: diethyl bromomalonate, ethyl 2-chloro-3-oxobutanoate, ethyl 2-bromocyanoacetate, 2-bromo-5,5-dimethylcyclohexan-1,3-dione, and bromomalononitrile. The boiling of 1a with ethyl 2-bromocyanoacetate in mixture of ethanol and EtONa results in intramolecular cyclization and formation of thiazolo[3,2-a]pyrimidin-5-one 3. Interaction of 1a with 3-chloropentane-2,4-dione and 2-bromo-1,3-diphenylpropane-1,3-dione yielded corresponding S-substituted thiopyrimidines 4a,4b. In general, the products of 1b S-alkylation are less prone to sulfur extrusion. Reaction of 1b with diethyl bromomalonate in the absence of EtONa stops at the S-alkylation step, while in the presence of EtONa in ethanol or PPh3in dioxane 2-(ethoxycarbonylmethyl)thio-6-phenyl-1,3-dihydropyrimidin-4(1H)-one 6 is formed exclusively. Molecular structure and crystal structure of 2-(1,1-diethoxycarbonylmethyliden)-6-methyl-1,3-dihydropyrimidin-4(1H)-one 2a are discussed.
Synthesis of pyridinylketones, and their cyclic derivatives produced from 6-methyl-2-thiouracil
Yavolovskii,Grishchuk,Rakipov,Ivanov,Stepanov,Kamalov
scheme or table, p. 725 - 728 (2012/10/07)
A possibility to obtain pyrimidines, containing oxoalkyl moiety in 2 position of the ring from the available 6-methyl-2-thiouracil was shown.
The Eschenmoser coupling reaction under continuous-flow conditions
Singh, Sukhdeep,Michael Koehler,Schober, Andreas,Alexander Gross
supporting information; experimental part, p. 1164 - 1172 (2011/10/08)
The Eschenmoser coupling is a useful carbon-carbon bond forming reaction which has been used in various different synthesis strategies. The reaction proceeds smoothly if S-alkylated ternary thioamides or thiolactames are used. In the case of S-alkylated s
A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold
Kemp, Melissa M.,Wang, Qiu,Fuller, Jason H.,West, Nathan,Martinez, Nicole M.,Morse, Elizabeth M.,We?wer, Michel,Schreiber, Stuart L.,Bradner, James E.,Koehler, Angela N.
supporting information; experimental part, p. 4164 - 4169 (2011/08/10)
Histone deacetylases (HDACs) are enzymes involved in many important biological functions. They have been linked to a variety of cancers, psychiatric disorders, and other diseases. Since small molecules can serve as probes to study the relevant biological
The Chemistry of Pyrimidinethiols. II. The Preparation and Reaction of Some 2-Arenecarbonylmethylthiopyrimidines
Hurst, Derek T.,Beaumont, Claire,Jones, Derek T. E.,Kingsley, Deborah A.,Partridge, Julian D.,Rutherford, Trevor J.
, p. 1209 - 1219 (2007/10/02)
A number of 2-arenecarbonylmethylthiopyrimidin-4(1H)-ones has been synthesized.Those having H, Me or Pr as a 6-substituent undergo ready sulfur extrusion on heating in diphenyl ether to give 2-(arenecarbonylmethylene)-2,3-dihydropyrimidin-4(1H)-ones, but
