35563-27-0Relevant articles and documents
Supramolecular structures in three thiouracil derivatives: 5,6-trimethylene-2-sulfanylidene-1,2-dihydropyrimidin-4(3H)-one, 2-(4-fluorobenzylsulfanyl)-5,6-trimethylenepyrimidin-4(3H)-one and methyl 2-{[2-(4-fluorobenzylsulfanyl)-5,6-trimethylenepyrimidin-4-yl]oxy}acetate
Zhou, Yu-Jun,Lv, Jing,Yu, Kai,Ma, Jian-Ping,Guo, Dian-Shun
, p. 416 - 420 (2014)
The molecules of the title compounds, C7H8N 2OS, (1), C14H13FN2OS, (2), and C17H17FN2O3S, (3), crystallize in the space groups C2/m, C2/c and Ia, respectively. Compounds (1) and (2), an S-alkylated derivative of (1), consist of only one symmetry-independent molecule, while (3), an O-alkylated derivative of (2), contains two independent molecules in the asymmetric unit. The molecules of (1) sit on crystallographic mirror planes. In the supramolecular structure of (1), a combination of N - H?O and N - H?S hydrogen bonds creates a molecular strap with C(6) and R 2 2(8) motifs, which is further stabilized by an S?S contact. In the packing of (2), a one-dimensional molecular column is made up of two kinds of dimers. One dimer, with an R 2 2(18) motif, is formed by a pair of C - H?O soft hydrogen bonds and the other, with an R 2 2(8) motif, is produced via a pair of N - H?O hard hydrogen bonds. In the packing of (3), molecules A and B form two different types of one-dimensional chain by intermolecular C - H?N hydrogen bonds, and by C?N and O?S contacts, respectively. Two such kinds of chain are connected alternately via interchain C - H?O hydrogen bonds, giving a two-dimensional sheet. Finally, a three-dimensional supramolecular structure is formed through weak intersheet C - H?F hydrogen bonds. The study of the molecular and supramolecular structures of thiouracil derivatives is significant in the development of lipoprotein-associated phospholipase A2 inhibitors.
Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties
Campiani,Morelli,Nacci,Fattorusso,Ramunno,Novellino,Greenwood,Liljefors,Griffiths,Sinclair,Reavy,Kristensen,Pickering,Schousboe,Cagnotto,Fumagalli,Mennini
, p. 4501 - 4504 (2001)
(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca2+]i, and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.
RADIOLABELED DARAPLADIB AND ANALOGS THEREOF AND THEIR USE AS IMAGING COMPOUNDS
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Page/Page column 29, (2019/04/26)
The present inventors have developed new radiolabeled Darapladib and analogs thereof which can be used for the specific detection of vulnerable atherosclerotic plaques by targeting lipoprotein-associated phospholipase A2 (Lp-PLA2) which is a biomarker of
Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis
Guibbal, Florian,Bénard, Sébastien,Patché, Jessica,Meneyrol, Vincent,Couprie, Jo?l,Yong-Sang, Jennyfer,Meilhac, Olivier,Jestin, Emmanuelle
supporting information, p. 787 - 792 (2018/01/17)
Darapladib is one of the most potent Lp-PLA2 (Lipoprotein-associated phospholipase A2) inhibitor with an IC50 of 0.25 nM. We demonstrate that a crucial step of Darapladib synthesis was not correctly described in the litera
SELECTIVE MATRIX METALLOPROTEINASE-13 INHIBITORS
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Paragraph 0054; 0055; 0056; 0057, (2019/01/06)
We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative
Laccase-catalyzed green synthesis and cytotoxic activity of novel pyrimidobenzothiazoles and catechol thioethers
Abdel-Mohsen,Conrad,Harms,Nohr,Beifuss
, p. 17427 - 17441 (2017/03/31)
The laccase-catalyzed reaction between unsubstituted catechol and 2-thioxopyrimidin-4(1H)-ones using aerial O2 as the oxidant delivers novel pyrimidobenzothiazoles with high yields in an aqueous solvent system under mild reaction conditions. With 4-substituted catechols, catechol thioethers are formed exclusively. The synthetic protocols developed provide a sustainable approach for these compound classes. In addition, the cytotoxicity of the products against HepG2 cell line is reported. Most compounds exhibit antiproliferative activities with IC50 values at the micromolar level. A structure-activity relationship study will facilitate the further development of these compounds as cytotoxic agents.
HETEROARYL DERIVATIVES AS SEPIAPTERIN REDUCTASE INHIBITORS
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Paragraph 00243-00246, (2017/05/31)
Inhibitors of sepiapterin reductase of formula (I) or (I'), wherein the substituents are defined as in the claims, and uses of sepiapterin reductase inhibitors in analgesia, treatment of acute and chronic pain, anti-inflammation, and immune cell regulation are disclosed.
Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors
Choi, Jun Yong,Fuerst, Rita,Knapinska, Anna M.,Taylor, Alexander B.,Smith, Lyndsay,Cao, Xiaohang,Hart, P. John,Fields, Gregg B.,Roush, William R.
supporting information, p. 5816 - 5825 (2017/07/22)
We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative
Identification of novel, exosite-binding matrix metalloproteinase-13 inhibitor scaffolds
Roth, Joshua,Minond, Dmitriy,Darout, Etzer,Liu, Qin,Lauer, Janelle,Hodder, Peter,Fields, Gregg B.,Roush, William R.
supporting information; scheme or table, p. 7180 - 7184 (2012/01/15)
Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhibitor 4, discovered through high-throughput screening, were synthesized to investigate structure-activity relationships in this inhibitor series. Systematic modifications of 4 led to the discovery of MMP-13 inhibitors 20 and 24 which are more selective than 4 against other MMPs. Compound 20 is also approximately fivefold more potent as an MMP-13 inhibitor than the original HTS-derived lead compound 4.
Design and synthesis of novel pyrazole-based Lp-PLA2 inhibitors
Wang, Yi,Xu, Weiren,Shao, Hua,Xie, Yafei,Wang, Jianwu
experimental part, p. 2039 - 2048 (2012/03/26)
A series of novel pyrazole-based lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors have been designed and synthetized by a variety of acetophenones via a 10-step convergent approach. The synthetic approach is carefully opt
