166096-57-7Relevant academic research and scientific papers
Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions
Abdel-Aziz, Alaa A.-M.,Angeli, Andrea,El-Azab, Adel S.,Hammouda, Mohammed E.A.,El-Sherbeny, Magda A.,Supuran, Claudiu T.
, p. 260 - 268 (2019)
Trimellitimides 6–21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6–11 a
Pyrazole-isoindoline-1,3-dione hybrid: A promising scaffold for 4-hydroxyphenylpyruvate dioxygenase inhibitors
He, Bo,Dong, Jin,Lin, Hong-Yan,Wang, Meng-Yao,Li, Xian-Kai,Zheng, Bai-Feng,Chen, Qiong,Hao, Ge-Fei,Yang, Wen-Chao,Yang, Guang-Fu
, (2019/10/28)
The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-benzoylethen-1-ol and isoindoline-1,3-dione fragments. The results of the in vitro tests indicated that the newly synthesized compounds showed good HPPD inhibitory activity with IC50 values against the recombinant Arabidopsis thaliana HPPD (AtHPPD) ranging from 0.0039 ?M to over 1 ?M. Most promisingly, compound 4ae, 2-benzyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)isoindoline-1,3-dione, showed the highest AtHPPD inhibitory activity with a Ki value of 3.92 nM, making it approximately 10 times more potent than pyrasulfotole (Ki = 44 nM) and slightly more potent than mesotrione (Ki = 4.56 nM). In addition, the cocrystal structure of the AtHPPD-4ae complex was successfully resolved at a resolution of 1.8 ?. The X-ray diffraction analysis indicated that the two carbonyl groups of 2-benzoylethen-1-ol formed a bidentate chelating interaction with the metal ion, while the isoindoline-1,3-dione moiety formed pronounced π-π stacking interactions with Phe381 and Phe424. Moreover, water-mediated hydrogen bonding interactions were observed between Asn282 and the nitrogen atoms of the pyrazole ring of 4ae. The above results showed that the pyrazole-isoindoline-1,3-dione hybrid is a promising scaffold for developing HPPD inhibitors.
Design and synthesis of phthalimide-type histone deacetylase inhibitors
Shinji, Chihiro,Nakamura, Takanori,Maeda, Satoko,Yoshida, Minoru,Hashimoto, Yuichi,Miyachi, Hiroyuki
, p. 4427 - 4431 (2007/10/03)
Several hydroxamic acid derivatives with a substituted phthalimide group as a linker and/or cap structure, prepared during structural development studies based on thalidomide, were found to have histone deacetylase (HDAC)-inhibitory activity. Structure-activity relationship studies indicated that nature of the substituent introduced at the phthalimide nitrogen atom, introduction of a hydroxamic acid structure, and distance between the N-hydroxyl group and the cap structure are important for HDAC-inhibitory activity.
