305835-76-1Relevant academic research and scientific papers
Discovery of quinazolinyl-containing benzamides derivatives as novel HDAC1 inhibitors with in vitro and in vivo antitumor activities
Zhang, Zixue,Zhang, Qingwei,Zhang, Hao,Jiao, Minru,Guo, Zheng,Peng, Xinyan,Fu, Lei,Li, Jianqi
, (2021/10/16)
A series of quinazolinyl-containing benzamide derivatives were designed, synthesized and evaluated for their in vitro histone deacetylase 1 (HDAC1) inhibitory activities. Compounds 11a surpassed the known class I selective HDAC inhibitor MS-275 in both HDAC1 enzymatic inhibitory activity and cellular anti-proliferative activity against a selected set of cancer cell types (Hut78, K562, Hep3B and HCT116 cells) with no observed effects on human normal cells. In particular, compound 11a inhibited HDAC1 over the other tested HDACs isoforms (HDAC2, HDAC6 and HDAC8) with acceptable safety profiles. Moreover, compound 11a displayed favorable oral pharmacokinetic properties and showed significant antitumor activity in the A549 tumor xenograft model in vivo.
Quinazoline-Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity
Hieu, Doan Thanh,Anh, Duong Tien,Hai, Pham-The,Huong, Le-Thi-Thu,Park, Eun Jae,Choi, Jeong Eun,Kang, Jong Soon,Dung, Phan Thi Phuong,Han, Sang-Bae,Nam, Nguyen-Hai
, (2018/06/20)
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a?–?4i, 6a?–?6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g?–?4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.
4-Aminoquinazoline Derivatives and Uses Thereof
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Paragraph 0090, (2014/09/03)
The present invention provides a 4-aminoquinazoline derivative having the chemical structure of the following formula, and the use thereof. It is demonstrated by the pharmacological experiment that, the compound or a salt thereof according to the present
4-AMINOQUINAZOLINE DERIVATIVES AND USES THEREOF
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Paragraph 0018; 0078, (2014/04/03)
The present invention provides a 4-aminoquinazoline derivative having the chemical structure of the following formula, and the use thereof. It is demonstrated by the pharmacological experiment that, the compound or a salt thereof according to the present
Synthesis of two bi-functional ligands for the QUEST three-hybrid system
Baker,Firestine,Smithrud,Salinas,Benkovic
, p. 7009 - 7012 (2007/10/03)
The synthesis is described for two bi-functional ligands (1) and (2) that have been used as chemical inducers of dimerization for QUEST,1 a three-hybrid system designed to detect novel enzyme activity in vivo. (C) 2000 Elsevier Science Ltd.
