19749-86-1Relevant academic research and scientific papers
Novel 4-(piperazin-1-yl)quinolin-2(1H)-one bearing thiazoles with antiproliferative activity through VEGFR-2-TK inhibition
Hassan, Abdelfattah,Badr, Mohamed,Hassan, Heba A.,Abdelhamid, Dalia,Abuo‐Rahma, Gamal El‐Din A.
, (2021/05/10)
A new series of 2-(4-(2-oxo-1,2-dihydroquinolin-4-yl)piperazin-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivatives were synthesized and evaluated for anticancer activity. All target compounds showed anticancer activity higher than that of their 2-oxo-4-piperazinyl-1,2-dihydroquinolin-2(1H)-one precursors. Multidose testing of target compounds was performed against breast cancer T-47D cell line. Five compounds showed higher cytotoxic activity than Staurosporine. The dihalogenated derivative showed the best cytotoxic activity with IC50 2.73 ± 0.16 μM. In addition, the VEGFR-2 inhibitory activity of all synthetic compounds was evaluated. Two compounds of 6-fluoro-4-(piperazin-1-yl)quinolin-2(1H)-ones showed inhibitory activity comparable to sorafenib with IC50 46.83 ± 2.4, 51.09 ± 2.6 and 51.41 ± 2.3 nM, respectively. The cell cycle analysis of two compounds namely, 2-(4-(6-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)piperazin-1-yl)-N-(4-phenylthiazol-2-yl)acetamide and N-(4-(4-chlorophenyl)thiazol-2-yl)-2-(4-(2-oxo-1-phenyl-1,2-dihydroquinolin-4-yl)piperazin-1-yl)acetamide revealed that the arrest of cell cycle occurred at S phase. In apoptosis assay, the same two compounds were able to induce significant levels of early and late apoptosis. In a similar manner to Sorafenib, docking of target compounds with VEGFR-2 protein 4ASD showed HB with Cys919 in hinge region of enzyme and HB with both Glu885 and Asp1046 in gate area. Using SwissADME, all target compounds were predicted to be highly absorbed from gastrointestinal tract with no BBB permeability. It is clear that the two compounds are promising antiproliferative candidates that require further optimization.
HETEROCYCLIC COMPOUNDS AS CLASS II PHOSPHOINOSITIDE 3-KINASE INHIBITORS
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Page/Page column 83; 87; 88; 93; 94, (2019/12/28)
The present application relates to compounds of formula (1) and their use as medicament, in particular for the treatment of a medical condition associated with defective PI3K signalling.
Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1
Piechowicz, Katarzyna A.,Truong, Eric C.,Javed, Kashif M.,Chaney, Rachelle R.,Wu, Johnny Y.,Phuan, Puay W.,Verkman, Alan S.,Anderson, Marc O.
, p. 1362 - 1368 (2016/10/09)
Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca2+ activated Cl? channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 μM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ～1 μM for inhibition of TMEM16A chloride conductance.
Studies on Cerebral Protective Agents. VIII. Synthesis of 2-Aminothiazoles and 2-Thiazolecarboxamides with Anti-anoxic Activity
Okhubo, Mitsuru,Kuno, Atsushi,Nakanishi,Isao,Takasugi, Hisashi
, p. 1497 - 1504 (2007/10/03)
Various 2-aminothiazoles (2a-s and 3a-g) and 2-thiazolecarboxamides (4a-h), possessing a nitrogeneous basic moiety at the C-2 position of the thiazole ring, were prepared and tested for anti-anoxic (AA) activity in mice.Among them, N-4-(3-trifluoromethylphenyl)-2-thiazolecarbaxamide hydrochloride (4e, FR108143) (minimum effective doses of 3,2 mg/kg i.p. and 10 mg/kg p.o., respectively) exhibited more potent AA activity than either FK360 or compound 1, each of which has a nitrogeneous basic moiety at the C-5 position.The structure-activity relationship with regard to AA activity of this series of compounds are discussed, and the three-dimensional electrostatic potentials (3D-MEP) around the basic nitrogen atom of FK360 and the thiazole derivative (4e) are compared.Key words cerebral protective agent; anti-anoxia; 2-aminothiazole; 2-thiazolecarboxamide; structure-activity relationship; FK360
