78502-85-9Relevant academic research and scientific papers
Design, synthesis, and antitumor activity evaluation of pretubulysin analogs
Xu, Xiangrong,Fan, Meixia,Qi, Junhui,Yao, Lei
, p. 341 - 351 (2021/06/14)
Pretubulysin, a biosynthetic precursor of the tubulysins, shows potent biological activity in a variety of tumor cell lines. Although there are several total synthesis routes to tubulysin and pretubulysin reported, the commercialization still has been hampered due to the complexity of the structure. To find structurally simpler pretubulysin analogs, a series of 2-(3-(methylamino)propyl)thiazole-4-carboxamides are designed and synthesized, and their anticancer activities are screened using MCF-7 (breast cancer), and NCI-H157 (lung cancer) cell lines. Taxol (IC50?=?0.01?μM) and pretubulysin are used as the control. Compounds 8c (IC50?=?0.05?μM, MCF-7; 0.09?μM, NCI-H157) and 8h (IC50?=?0.01?μM, MCF-7; 0.02?μM, NCI-H157) exhibited certain antitumor activities comparable to those of Taxol. The urea analogs of pretubulysin might represent a promising scaffold for the further development of novel antitumor drugs.
Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554
Maezaki, Hironobu,Tawada, Michiko,Yamashita, Tohru,Banno, Yoshihiro,Miyamoto, Yasufumi,Yamamoto, Yoshio,Ikedo, Koji,Kosaka, Takuo,Tsubotani, Shigetoshi,Tani, Akiyoshi,Asakawa, Tomoko,Suzuki, Nobuhiro,Oi, Satoru
supporting information, p. 3565 - 3571 (2017/07/07)
We report a design strategy to obtain potent DPP-4 inhibitors by incorporating salt bridge formation with Lys554 in the S1′ pocket. By applying the strategy to the previously identified templates, quinoline 4 and pyridines 16a, 16b, and 17 have been identified as subnanomolar or nanomolar inhibitors of human DPP-4. Docking studies suggested that a hydrophobic interaction with Tyr547 as well as the salt bridge interaction is important for the extremely high potency. The design strategy would be useful to explore a novel design for DPP-4 inhibitors having a distinct structure with a unique binding mode.
N-Bromosuccinimide Bromination of Substituted Methylthiazoles
Krieg, Benno,Mittner, Juergen
, p. 623 - 632 (2007/10/02)
Bromination of methylthiazoles with one unsubstituted position by N-bromosuccinimide may take place either at the methyl group, at the heterocyclic nucleus, or at both positions according to the nature of the second substituent.The ethoxycarbonyl group in the compounds 1a-3a directs the bromine into the side chain.So it is possible to obtain the tribromomethyl compounds 1d and 2d without bromination of the thiazole nucleus.In the phenyl-substituted methylthiazoles 4a-6a bromination takes place in the methyl group and in the heterocyclic nucleus. - The bromomethylthiazoles 1b-3b yield the vinylthiazoles 1k-3k by Wittig reaction.
