476317-31-4Relevant academic research and scientific papers
Synthesis, cytotoxicity and anti-metastatic properties of new pyridyl–thiazole arene ruthenium(II) complexes
Wang, Li,He, Yihui,Xiang, Guangya,Shang, Xianmei
, (2018/03/21)
A series of novel ruthenium(II)–cymene complexes (1–8) containing substituted pyridyl–thiazole ligands, [Ru(η6-p-cymene)(L)Cl]Cl (L = N,N-chelating derivatives), have been synthesized and characterized using elemental analysis, infrared, 1H NMR and 13C NMR spectroscopies and mass spectrometry. All these complexes not only display marked cytotoxicity in vitro against three different human cancer cell lines (HeLa, A549 and MDA-MB-231), but also exhibit promising anti-metastatic activity at sub-cytotoxic concentrations. Cell cycle analysis shows that the ruthenium(II) complex-induced growth inhibition was mainly caused by S-phase cell cycle arrest. Further protein level analysis suggests that compound 5 may exert antitumor activity via a p53-independent mechanism.
Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents
Mjambili, Faith,Njoroge, Mathew,Naran, Krupa,De Kock, Carmen,Smith, Peter J.,Mizrahi, Valerie,Warner, Digby,Chibale, Kelly
, p. 560 - 564 (2014/01/23)
A series of compounds derived from the 2-amino-4-(2-pyridyl) thiazole scaffold was synthesized and tested for in vitro antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, antiplasmodial activity against the chloroquine sensitive NF54 Plasmodium falciparum strain and cytotoxicity on a mammalian cell line. Optimal antimycobacterial activity was found with compounds with a 2-pyridyl ring at position 4 of the thiazole scaffold, a substituted phenyl ring at the 2-amino position, and an amide linker between the scaffold and the substituted phenyl. The antiplasmodial activity was best with compounds that had the phenyl ring substituted with hydrophobic electron withdrawing groups.
Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
Meissner, Anja,Boshoff, Helena I.,Vasan, Mahalakshmi,Duckworth, Benjamin P.,Barry III, Clifton E.,Aldrich, Courtney C.
, p. 6385 - 6397 (2013/10/22)
A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl) -1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ～300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of ～10-5.
Discovery and in vitro and in vivo profiles of 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as novel class of an orally active metabotropic glutamate receptor 1 (mGluR1) antagonist
Satoh, Atsushi,Nagatomi, Yasushi,Hirata, Yukari,Ito, Satoru,Suzuki, Gentaroh,Kimura, Toshifumi,Maehara, Shunsuke,Hikichi, Hirohiko,Satow, Akio,Hata, Mikiko,Ohta, Hisashi,Kawamoto, Hiroshi
scheme or table, p. 5464 - 5468 (2010/06/19)
We identified 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide 27 as a potent mGluR1 antagonist. The compound possessed excellent subtype selectivity and good PK profile in rats. It also demonstrated relatively potent a
