175137-08-3Relevant articles and documents
Synthesis of tetrasubstituted thieno[3,2-b]pyridin-5(4H)-one derivatives as a heterocyclic scaffold for multisite-specific fluorous fluorescent tagging and fluorous solid-phase extraction
Jeon, Moon-Kook,Yi, Su-Jin,Son, Seung Uk
, p. 1204 - 1210 (2016)
Tetrasubstituted thieno[3,2-b]pyridin-5(4H)-one derivatives were selected as a highly functionalized heterocyclic scaffold for a multisite-specific tagging process utilizing a previously devised fluorous fluorescent tag system. A suitable synthetic method was established for the 7-alkoxy-2,4,6-trisubstituted-thieno[3,2-b] pyridin-5(4H)-one derivatives, and incorporating t-butoxycarbonyl-functionalized building blocks into the reaction sequence produced precursors that could be used in the tagging process. Fluorous solid-phase extraction facilitated the purification of the tagged target compounds after a series of reactions, including t-Bu deprotection/N-hydroxysuccinimidyl ester formation/amidation.
EIF4E INHIBITORS AND USES THEREOF
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Paragraph 00506; 00524; 00553, (2021/09/11)
The present invention provides compounds inhibiting elF4E activity and compositions and methods of using thereof.
Solid-phase synthetic method for N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives
Ahn, Seohyeon,Jeon, Moon-Kook
, (2021/06/12)
Herein, we describe a solid-phase synthetic method for synthesizing N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives. The derivatives consist of the biologically active 6-phenylthieno[3,2-d]pyrimidine scaffold. The template mediated synthetic strategy involving Suzuki coupling reactions between methyl 3-amino-5-bromothiophene-2-carboxylate and arylboronic acids afforded methyl 3-amino-5-arylthiophene-2-carboxylates. Cyclocondensation reactions involving methyl 3-amino-5-arylthiophene-2-carboxylates and methyl cyanoformate afforded esters, that when subjected to hydrolysis reactions yielded 6-aryl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-carboxylic acids (template compounds). These carboxylic acid templates were coupled with primary alkylamine-loaded acid-sensitive methoxybenzaldehyde (AMEBA) resins. The amide coupling reactions were followed by direct amination reactions mediated by benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP). The compounds were subsequently cleaved from the solid support, purified using the reverse phase-high performance liquid chromatography technique (RP-HPLC), and passed through a strong anion exchange (SAX) resin pretreated with water to yield the N-alkyl-4-alkylamino-6-arylthieno[3,2-d]pyrimidine-2-carboxamide derivatives. The reaction conditions for the solid-phase transformations were optimized using a solution-phase model using 2,4-dimethoxybenzyl-protected isobutylamine as a reactant. 2,4-Dimethoxybenzyl-protected isobutylamine, and not AMEBA resin-loaded isobutylamine was used during the process. Substituent variation experiments were performed using 6-aryl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-2-carboxylic acids and a variety of primary and secondary amine building blocks. Additionally, we could include the Suzuki coupling step in a modified solid-phase synthetic sequence.
2-Bromo-2-chloro-3-arylpropanenitriles as C-3 Synthons for the Synthesis of Functionalized 3-Aminothiophenes
Batsyts, Sviatoslav,Shehedyn, Maksym,Goreshnik, Evgeny A.,Obushak, Mykola D.,Schmidt, Andreas,Ostapiuk, Yurii V.
, p. 7842 - 7856 (2019/12/24)
2-Bromo-2-chloro-3-arylpropanenitriles can be prepared by Meerwein reaction from 2-chloroacrylonitrile and various aryldiazonium salts under copper(II) bromide catalysis. They proved to be stable compounds which form 2-chlorocinnnamonitriles upon treatment with bases. Reaction of the title compounds with substituted thioglycolates gave substituted 3-aminothiophenes which have not yet been accessible by other routes. Three-component reactions with the title compound, sodium sulfide and bromonitromethane, chloroacetonitrile, or ethyl 4-chloroacetoacetate gave 2-nitro- and 2-cyano-substituted 3-aminothiophenes, and thienopyridinediones in high yields and in one single step, respectively.
One-pot synthesis of 2-substituted thieno[3,2-b]indoles from 3-aminothiophene-2-carboxylates through in situ generated 3-aminothiophenes
Irgashev, Roman A.,Steparuk, Alexander S.,Rusinov, Gennady L.
supporting information, (2019/09/30)
A convenient protocol for one-pot synthesis of thieno[3,2-b]indoles, bearing aromatic, thien-2-yl or styryl fragments at C-2 position, from easily accessible 5-substituted 3-aminothiophene-2-carboxylates using the Fischer indolization reaction, was develo
Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2- d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors
Romagnoli, Romeo,Prencipe, Filippo,Oliva, Paola,Baraldi, Stefania,Baraldi, Pier Giovanni,Schiaffino Ortega, Santiago,Chayah, Mariem,Kimatrai Salvador, Maria,Lopez-Cara, Luisa Carlota,Brancale, Andrea,Ferla, Salvatore,Hamel, Ernest,Ronca, Roberto,Bortolozzi, Roberta,Mariotto, Elena,Mattiuzzo, Elena,Viola, Giampietro
supporting information, p. 1274 - 1290 (2019/01/30)
The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3′,4′,5′-trimethoxyanilino)thieno[3,2-d]pyrimidine derivatives were discovered as novel dual tubulin polymerization and EGFR kinase inhibitors. The 4-(3′,4′,5′-trimethoxyanilino)-6-(p-tolyl)thieno[3,2-d]pyrimidine derivative 6g was the most potent compound of the series as an antiproliferative agent, with half-maximal inhibitory concentration (IC50) values in the single- or double-digit nanomolar range. Compound 6g bound to tubulin in the colchicine site and inhibited tubulin assembly with an IC50 value of 0.71 μM, and 6g inhibited EGFR activity with an IC50 value of 30 nM. Our data suggested that the excellent in vitro and in vivo profile of 6g may be derived from its dual inhibition of tubulin polymerization and EGFR kinase.
Potent, selective, and orally efficacious antagonists of melanin-concentrating hormone receptor 1
Tavares, Francis X.,Al-Barazanji, Kamal A.,Bigham, Eric C.,Bishop, Michael J.,Britt, Christy S.,Carlton, David L.,Feldman, Paul L.,Goetz, Aaron S.,Grizzle, Mary K.,Guo, Yu C.,Handlon, Anthony L.,Hertzog, Donald L.,Ignar, Diane M.,Lang, Daniel G.,Ott, Ronda J.,Peat, Andrew J.,Zhou, Hui-Qiang
, p. 7095 - 7107 (2008/04/18)
The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pKas and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.
