16234-10-9Relevant articles and documents
A facile synthesis of new 4-(phenylamino)thieno[3,2-d]pyrimidines using 3-aminothiophene-2-carboxamide
Song, Yang-Heon
, p. 33 - 34 (2007)
Several new 4-(phenylamino)thieno[3,2-d]pyrimidine derivatives 3 were synthesized in high yield by the reaction of aniline derivatives and 4-chlorothieno[3,2-d]pyrimidine that can be easily prepared using 3-aminothiophene-2-carboxamide.
Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity
Munchhof, Michael J.,Beebe, Jean S.,Casavant, Jeffery M.,Cooper, Beth A.,Doty, Jonathan L.,Higdon, R. Carla,Hillerman, Stephen M.,Soderstrom, Catherine I.,Knauth, Elisabeth A.,Marx, Matthew A.,Rossi, Ann Marie K.,Sobolov, Susan B.,Sun, Jianmin
, p. 21 - 24 (2004)
Novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase. The synthesis and SAR of these compounds is presented, along with successful efforts to diminish EGFR activity present in the lead series.
Chemical Space Exploration around Thieno[3,2- d]pyrimidin-4(3 H)-one Scaffold Led to a Novel Class of Highly Active Clostridium difficile Inhibitors
Shao, Xuwei,Abdelkhalek, Ahmed,Abutaleb, Nader S.,Velagapudi, Uday Kiran,Yoganathan, Sabesan,Seleem, Mohamed N.,Talele, Tanaji T.
, p. 9772 - 9791 (2019)
Clostridium difficile infection (CDI) is the leading cause of healthcare-associated infection in the United States. Therefore, development of novel treatments for CDI is a high priority. Toward this goal, we began in vitro screening of a structurally diverse in-house library of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), which yielded a hit compound, 2-methyl-8-nitroquinazolin-4(3H)-one (2) with moderate potency (MIC = 312/156 μM). Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin-4(3H)-one) with improved potency (MIC = 19/38 μM), selectivity over normal gut microflora, CC50s > 606 μM against mammalian cell lines, and acceptable stability in simulated gastric and intestinal fluid. Further optimization of 6a at C2-, N3-, C4-, and C7-positions resulted in a library of >50 compounds with MICs ranging from 3 to 800 μM against clinical isolates of C. difficile. Compound 8f (MIC = 3/6 μM) was identified as a promising lead for further optimization.
Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors
Wang, Jiang,Su, Mingbo,Li, Tingting,Gao, Anhui,Yang, Wei,Sheng, Li,Zang, Yi,Li, Jia,Liu, Hong
, p. 293 - 299 (2017)
New thienopyrimidine hydroxamic acid derivatives as HDACs inhibitors were designed, synthesized and evaluated. All compounds were evaluated for their ability to inhibit recombinant human HDAC1, HDAC3, and HDAC6 isoforms and in vitro anti-proliferative act
Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design
Wang, Linxiao,Zhang, Qian,Wang, Zhe,Zhu, Wufu,Tan, Ninghua
, (2021/07/09)
Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine/N-methylpicolinamide derivatives substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds showed selectivity toward the A549 cell lines and the most promising compound 38 could inhibit TAK1 kinase and NF-κB signaling pathway with the IC50 values of 0.58 and 0.84 μM. Moreover, 38 can induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound 38 could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. What's more, the studies of docking, molecular dynamics, MM/PBSA and frequency analysis theoretically supported the conclusions of the bioevaluation.
An Efficient Second-Generation Manufacturing Process for the pan-RAF Inhibitor Belvarafenib
Zell, Daniel,Dalziel, Michael E.,Carrera, Diane E.,Stumpf, Andreas,Bachmann, Stephan,Mercado-Marin, Eduardo,Koenig, Stefan G.,Zhang, Haiming,Gosselin, Francis
supporting information, p. 2338 - 2350 (2021/09/28)
Herein, the development of a streamlined manufacturing process for the pan-RAF inhibitor belvarafenib (GDC-5573) is reported. The process to belvarafenib features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access the penultimate intermediate 3. The final amide coupling was accomplished by a mild and safe protocol employing N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate as the coupling reagent, which afforded belvarafenib on a multikilogram production scale after recrystallization.
Commercial Copper-Catalyzed Aerobic Oxidative Synthesis of Quinazolinones from 2-Aminobenzamide and Methanol
Chatwichien, Jaruwan,Choommongkol, Vachira,Kerdphon, Sutthichat,Meepowpan, Puttinan,Rithchumpon, Puracheth,Sanghong, Patthadon,Singh, Thishana
supporting information, p. 2730 - 2734 (2020/05/18)
The focus of this study was the development of a new synthetic method for quinazolinones based on the principles of Green Chemistry. Quinazolinones were synthesized from 2-aminobenzamide using methanol as both the C1 source and a green solvent in the presence of base Cs2CO3. Additionally, a commercially available, economical copper complex was used as a catalyst in the reaction. The desired products were achieved in moderate to high yield with up to 99 % isolated yield.
6-Cinnamoyl-4-arylaminothienopyrimidines as highly potent cytotoxic agents: Design, synthesis and structure-activity relationship studies
Aghcheli, Ayoub,Bakhshaiesh, Tayebeh Oghabi,Esmaeili, Rezvan,Foroumadi, Alireza,Hasanvand, Zaman,Khalaj, Ali,Moghimi, Setareh,Nazeri, Elahe,Salarinejad, Somayeh,Toolabi, Mahsa
supporting information, (2019/11/03)
In this paper, we described the synthesis and cytotoxic activities of two new series of thieno[2,3-d]pyrimidine and thieno[3,2-d] pyrimidine derivatives. Most of the synthesized compounds had significant antiproliferative activities against PC3, MDA-MB-23
Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction
Fang, Sen-Biao,Li, Hui-Jing,Nan, Xiang,Wu, Rui,Wu, Yan-Chao,Zhang, Jing,Zhang, Zhi-Zhou
, (2020/06/04)
In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.
4-phenoxythiophene[3,2-d]pyrimido-alpha-amido thioamide compound as well as preparation method and application thereof
-
, (2020/11/12)
The invention relates to a 4-phenoxythiophene[3,2-d]pyrimido-alpha-amido thioamide compound I. The 4-phenoxythiophene[3,2-d]pyrimido-alpha-amido thioamide compound I is used as a tyrosine kinase inhibitor, especially a c-Met inhibitor. The invention also
