17417-67-3Relevant articles and documents
Molecular design, synthesis and in vitro biological evaluation of thienopyrimidine–hydroxamic acids as chimeric kinase HDAC inhibitors: a challenging approach to combat cancer
Abdel-Atty, Mona M.,Farag, Nahla A.,Serya, Rabah A. T.,Abouzid, Khaled A. M.,Mowafy, Samar
, p. 1290 - 1312 (2021/07/09)
A series of thieno[2,3-d]pyrimidine-based hydroxamic acid hybrids was designed and synthesised as multitarget anti-cancer agents, through incorporating the pharmacophore of EGFR, VEGFR2 into the inhibitory functionality of HDAC6. Three compounds (12c, 15b and 20b) were promising hits, whereas (12c) exhibited potent VEGFR2 inhibition (IC50=185 nM), potent EGFR inhibition (IC50=1.14 μM), and mild HDAC6 inhibition (23% inhibition). Moreover, compound (15c) was the most potent dual inhibitor among all the synthesised compounds, as it exhibited potent EGFR and VEGFR2 inhibition (IC50=19 nM) and (IC50=5.58 μM), respectively. While compounds (20d) and (7c) displayed nanomolar selective kinase inhibition with EGFR IC50= 68 nM and VEGFR2 IC50= 191 nM, respectively. All of the synthesised compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumour cell lines. Additionally, molecular docking studies and ADMET studies were carried out to gain further insight into their binding mode and predict the pharmacokinetic properties of all the synthesised inhibitors.
Synthesis and antitumor activity evaluation of some thienopyrimidine derivatives
Abou-Elmagd, Wael S. I.,Abou-Elregal, Mohsen K.,Hemdan, Magdy M.,Mohamed, Amira T. A.,Samir, Sandy S.,Youssef, Ahmed S. A.
supporting information, (2019/12/30)
Some novel thienopyrimidine derivatives were synthesized via the reaction of 5- methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-5-carbohydrazide with different carbonyl compounds such as anhydrides, acid chlorides, carbon disulfide, phenyl isothiocyanate, triethyl orthoformate, diethyl acetylene dicarboxylate, acetylacetone, pyrazole-4-carboxaldehyde, and isatin. Also, the reaction of this carbohydrazide derivative with sodium nitrite in the presence of hydrochloric acid to give the corresponding azide derivative was discussed. The latter azide derivative was reacted with different amines to give the corresponding diheteryl urea derivatives. The antitumor activity evaluation of some representative examples of the synthesized compounds was examined against HePG2 and MCF-7 cell lines. Some of the newly synthesized compounds showed significant activity.
Design, synthesis, neuroprotective, antibacterial activities and docking studies of novel thieno[2,3-d]pyrimidine-alkyne Mannich base and oxadiazole hybrids
Triloknadh, Settypalli,Venkata Rao, Chunduri,Nagaraju, Kerru,Hari Krishna, Nallapaneni,Venkata Ramaiah, Chintha,Rajendra, Wudayagiri,Trinath, Daggupati,Suneetha, Yeguvapalli
supporting information, p. 1663 - 1669 (2018/03/29)
A series of thieno[2,3-d]pyrimidine alkyne Mannich base derivatives (7a-e, 8a-e) and thieno[2,3-d]pyrimidine 1,3,4-oxadiazole derivatives (9a-e, 10a-e) have been synthesized and evaluated for their neuroprotective and neurotoxicity activities where 9a, 10d displayed good neuroprotection 10.6 and 11.88 μg/mL respectively against the H2O2 induced cell death at the EC50 values and 9b, 9d showed respective toxic effects on PC12 cells at CC50 86.12 and 94.16 μg/mL. Compounds 9a, 9e, 10a and 10b showed strong antibacterial activity against two gram positive (S. aureus, B. subtilis) and two gram-negative strains (E. coli, P. aeruginosa) and showed good binding affinities with C(30) carotenoid dehydrosqualene synthase, Gyrase A and LpxC. This is the first report for the demonstration of thieno[2,3-d] pyrimidine derivatives as promising neuroprotective agents against H2O2 induced neurotoxicity on PC12 cells.
