35104-74-6Relevant academic research and scientific papers
Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
Zhou, Xia,Tan, Yuping,Gou, Kun,Tao, Lei,Luo, Yuan,Zhou, Yue,Zuo, Zeping,Sun, Qingxiang,Luo, Youfu,Zhao, Yinglan
, (2021/07/26)
Serine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 μM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest. Collectively, our results suggest that b36 is a novel PHGDH inhibitor, which could be a promising modulator to reprogram the serine synthesis pathway and might be a potential anticancer lead worth further exploration.
Enantioselective Synthesis of Spiropyrazolone-Fused Cyclopenta[ c]chromen-4-ones Bearing Five Contiguous Stereocenters via (3+2) Cycloaddition
Khairnar, Pankaj V.,Su, Yin-Hsiang,Edukondalu, Athukuri,Lin, Wenwei
, p. 12326 - 12335 (2021/08/24)
An enantioselective synthesis of spiropyrazolone-fused cyclopenta[c]chromen-4-ones is demonstrated via a (3+2) cycloaddition reaction. The reactions of 3-homoacylcoumarins and α,β-unsaturated pyrazolones in the presence of the cinchona-alkaloid derived hy
A three-component, general and practical route for diastereoselective synthesis of aza-spirocyclic pyrazolonesviaa decarboxylative annulation process
Awasthi, Annapurna,Yadav, Pushpendra,Tiwari, Dharmendra Kumar
, p. 2374 - 2383 (2021/02/16)
An efficient, general, and practical route for highly diastereoselective synthesis of aza-spirocyclic pyrazolones from easily available α-amino acids, aldehydes, and alkylidene pyrazolones by means of a decarboxylative annulation process is reported. This
Lewis-Base-Catalyzed [1 + 2 + 2] Annulation Reaction of Morita-Baylis-Hillman Carbonates with Unsaturated Pyrazolones: Construction of All-Stereogenic Carbon Cyclopentane-Fused Dispiropyrazolones
Liang, Jin-Yan,Shen, Shou-Jie,Chai, Xiao-Qian,Lv, Ting
, p. 12744 - 12752 (2018/10/09)
The first Lewis-base-catalyzed unexpected [1 + 2 + 2] annulation reaction between Morita-Baylis-Hillman carbonates and unsaturated pyrazolones was developed. The multicyclic cyclopentane-fused dispiropyrazolone constructions containing five contiguous ste
An asymmetric approach toward chiral multicyclic spirooxindoles from isothiocyanato oxindoles and unsaturated pyrazolones by a chiral tertiary amine thiourea catalyst
Chen, Qiao,Liang, Jinyan,Wang, Shoulei,Wang, Dong,Wang, Rui
, p. 1657 - 1659 (2013/03/14)
The first organocatalytic Michael-cyclization cascade reaction between isothiocyanato oxindoles and unsaturated pyrazolones has been developed. The multicyclic spiro[oxindole/thiobutyrolactam/pyrazolone] core structures containing three contiguous stereog
