27427-92-5Relevant articles and documents
Development of a new benzophenone-diketopiperazine-type potent antimicrotubule agent possessing a 2-pyridine structure
Hayashi, Yoshiki,Takeno, Haruka,Chinen, Takumi,Muguruma, Kyohei,Okuyama, Kohei,Taguchi, Akihiro,Takayama, Kentaro,Yakushiji, Fumika,Miura, Masahiko,Usui, Takeo,Hayashi, Yoshio
, p. 1094 - 1098 (2014)
A new benzophenone-diketopiperazine-type potent antimicrotubule agent was developed by modifying the structure of the clinical candidate plinabulin (1). Although the right-hand imidazole ring with a branched alkyl chain at the 5-position in 1 was critical for the potency of the antimicrotubule activity, we successfully substituted this moiety with a simpler 2-pyridyl structure by converting the left-hand ring from a phenyl to a benzophenone structure without decreasing the potency. The resultant compound 6b (KPU-300) exhibited a potent cytotoxicity, with an IC50value of 7.0 nM against HT-29 cells, by strongly binding to tubulin (Kd= 1.3 μM) and inducing microtubule depolymerization.
Screening Platform Based on Inductively Coupled Plasma Mass Spectrometry for β-Site Amyloid Protein Cleaving Enzyme 1 (BACE1) Inhibitors
Jin, Xin,Yang, Limin,Yan, Xiaowen,Wang, Qiuquan
, p. 1093 - 1099 (2021/05/06)
β-Site amyloid protein cleaving enzyme 1 (BACE1) is a promising therapeutic target for developing inhibitors to alleviate Alzheimer's disease (AD). Herein, we established an inductively coupled plasma mass spectrometry (ICPMS)-based inhibitor screening platform. A biotin-labeled lanthanide-coded peptide probe (LCPP; biotin-PEG2-EVNLDAEC-DOTA-Ln) was designed to determine the activity of BACE1 and evaluate the degree of inhibition of inhibitors. The platform was first validated with two commercially available inhibitors (BSI I and BSI IV) in terms of IC50 values and then applied to two newly designed inhibitors (inhibitors II and III) based on the crystal structure of BACE1 interacting with inhibitor I, and each of them contained an acylguanidine core structure. We found that their inhibition effects were improved as evaluated by the sensitive and accurate LCPP-ICPMS platform, demonstrating its ability for new drug screening.
Synthesizing process of nitrogen-heterocyclic high-selectivity aldehyde
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Paragraph 0014; 0022; 0023; 0035; 0041; 0048; 0054, (2017/09/05)
The invention relates to a synthesizing process of nitrogen-heterocyclic high-selectivity aldehyde. The synthesizing process is characterized in that when nitrogen-heterocyclic nitrogen atoms have hydrogen atoms, pyrrole, piperidine and pyrazole are used as the initial raw materials, and the pyrrole, the piperidine and the pyrazole are allowed to have reaction with piperidine-1-formaldehyde under nitrogen atom protection to obtain required nitrogen-atom ortho-position aldehyde; when nitrogen-heterocyclic nitrogen atoms have no hydrogen atoms, pyridine and pyrimidine are used to have reaction with the piperidine-1-formaldehyde to obtain the required nitrogen-atom ortho-position aldehyde. The synthesizing process is simple to operate, few in steps and high in selectivity and is a universal method using nitrogen heterocycle to synthesize the nitrogen ortho-position aldehyde.
