300816-22-2Relevant academic research and scientific papers
Discovery of novel akt1 inhibitor induces autophagy associated death in hepatocellular carcinoma cells
Yu, Meng,Zeng, Minghui,Pan, Zhaoping,Wu, Fengbo,Guo, Li,He, Gu
, (2020/02/03)
In this study, a series of thieno [2,3-d]pyrimidine derivatives were designed, synthesized and evaluated as novel AKT1 inhibitors. In vitro antitumor assay results showed that compounds 9d-g and 9i potently suppressed the enzymatic activities of AKT1 and
Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor
Fyfe, Tim J.,Kellam, Barrie,Mistry, Shailesh N.,Scammells, Peter J.,Lane, J. Robert,Capuano, Ben
, p. 474 - 490 (2019/03/07)
We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-μM affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i).
Design, synthesis, biological evaluation and molecular modeling study of new thieno[2,3-d]pyrimidines with anti-proliferative activity on pancreatic cancer cell lines
Salem, Mohamed S.H.,Abdel Aziz, Yasmine M.,Elgawish, Mohamed S.,Said, Mohamed M.,Abouzid, Khaled A.M.
, (2019/12/24)
Pancreatic cancer is one of the most challenging diseases with seven months only as median survival time due to its poor prognosis. Several enzymes are blamed for the progress of pancreatic cancer especially, platelet-derived growth factor receptors (PDGFRs), this in turn makes them promising targets for its treatment. In this study, twenty eight new compounds based on thieno[2,3-d]pyrimidine scaffold were synthesized as anti-pancreatic cancer agents mimicking the benzofuro[3,2-d]pyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds. Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound 9d showed the highest cytotoxicity with an IC50 value of 5.4 μM. Furthermore, 9d showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC50 value 0.155 μM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quantitative structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy.
Identification of 4-methoxythieno[2,3-d]pyrimidines as FGFR1 inhibitors
Balanda, A. O.,Bdzhola, V. G.,Kotey, I. M.,Pletnova, L. V.,Protopopov, M. V.,Prykhod’ko, A. O.,Starosyla, S. A.,Yarmoluk, S. M.
, p. 152 - 162 (2020/06/02)
Aim. To identify novel FGFR1 inhibitors using virtual screening approach. Methods. We used methods of organic synthesis, molecular docking via the Autodock 4.2.6 program package and in vitro biochemical tests with γ-32P. Results. In vitro experiments showed that 9 of 23 tested compounds possess inhibitory activity against FGFR1 with IC50 values in the range from 0.9 to 5.6 μM. Conclusions. Nine FGFR1 inhibitors were developed. The mode of compounds binding with the ATP-acceptor site was determined using molecular docking methods and the dependence of the compounds’ activity on the substituents R1, R4 and R5 was evaluated.
Design and synthesis of novel annulated thienopyrimidines as phosphodiesterase 5 (PDE5) inhibitors
El-Sharkawy, Lina Y.,El-Sakhawy, Rowaida A.,Abdel-Halim, Mohammad,Lee, Kevin,Piazza, Gary A.,Ducho, Christian,Hartmann, Rolf W.,Abadi, Ashraf H.
, (2018/04/20)
Novel cycloalkene-fused thienopyrimidine analogues with enhanced phosphodiesterase 5 (PDE5) inhibitory properties are presented. The structure of the reported scaffold was modulated through variation of the terminal cycloalkene ring size, as well as by va
Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication
Bassetto, Marcella,Leyssen, Pieter,Neyts, Johan,Yerukhimovich, Mark M.,Frick, David N.,Brancale, Andrea
, p. 31 - 47 (2016/08/01)
A structure-based virtual screening technique was applied to the study of the HCV NS3 helicase, with the aim to find novel inhibitors of the HCV replication. A library of ～450000 commercially available compounds was analysed in silico and 21 structures were selected for biological evaluation in the HCV replicon assay. One hit characterized by a substituted thieno-pyrimidine scaffold was found to inhibit the viral replication with an EC50value in the sub-micromolar range and a good selectivity index. Different series of novel thieno-pyrimidine derivatives were designed and synthesised; several new structures showed antiviral activity in the low or sub-micromolar range.
FLT3 INHIBITORS AND USES THEREOF
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Paragraph 00369-00370; 00569-00570, (2014/12/12)
The present invention provides methods of using compounds of formula I: or compositions thereof for the inhibition of FLT3, and the treatment of FLT3-mediated disorders.
IRAK INHIBITORS AND USES THEREOF
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Page/Page column 121, (2012/07/28)
The present invention relates to compounds and methods useful for inhibiting one or more interleukin-l receptor-associated kinases ("IRAK"). In some embodiments, a provided compound inhibits IRAK-1 and IRAK-4. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
Convenient and efficient synthesis of some novel fused thieno pyrimidines using gewald's reaction
Nirogi, Ramakrishna V.S.,Kambhampati, Sastri Rama,Kothmirkar, Prabhakar,Arepalli, Sobhanadri,Pamuleti, Narasimha Reddy G.,Shinde, Anil K.,Dubey
, p. 2835 - 2851 (2011/09/12)
Several functionalized thienopyrimidines were synthesized by a facile synthetic method, which includes Gewald's reaction, and were characterized by spectral and analytical data. These functionalized thienopyrimidines were converted to various new chemical
Design and synthesis of tetrahydropyridothieno[2,3-d]pyrimidine scaffold based epidermal growth factor receptor (EGFR) kinase inhibitors: The role of side chain chirality and michael acceptor group for maximal potency
Wu, Chia-Hsien,Coumar, Mohane Selvaraj,Chu, Chang-Ying,Lin, Wen-Hsing,Chen, Yi-Rong,Chen, Chiung-Tong,Shiao, Hui-Yi,Rafi, Shaik,Wang, Sing-Yi,Hsu, Hui,Chen, Chun-Hwa,Chang, Chun-Yu,Chang, Teng-Yuan,Lien, Tzu-Wen,Fang, Ming-Yu,Yeh, Kai-Chia,Chen, Ching-Ping,Yeh, Teng-Kuang,Hsieh, Su-Huei,Hsu, John T.-A.,Liao, Chun-Chen,Chao, Yu-Sheng,Hsieh, Hsing-Pang
scheme or table, p. 7316 - 7326 (2011/02/23)
HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 a
