73999-10-7Relevant articles and documents
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)
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.
Synthesis and antitumor evaluation of 5-(benzo[: D] [1,3]dioxol-5-ylmethyl)-4-(tert -butyl)- N -arylthiazol-2-amines
Wu,Fang,Tang,Xiao,Ye,Li,Hu
, p. 1768 - 1774 (2016/09/28)
A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1-C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.
Synthesis and Cytotoxicity in Vitro of N-Aryl-4-(Tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine
Ye, Jiao,Xiao, Meng-Wu,Xie, Xuan-Qing,Qiu, Shen-Yi,Dai, Ming-Chong,Li, Wan,Shen, Fang,Hu, Ai-Xi
, p. 627 - 631 (2018/01/18)
A series of novel N-aryl-4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amines were synthesized in a green way. H2O2-NaBr Brominating circulatory system was used in the synthesis of the key intermediate in a mild condition. All of the target compounds were confirmed by1H NMR and elemental analysis and tested for their cytotoxicity against two different human cancer cell lines. The cytotoxicity assay revealed that some of the title compounds showed moderate to strong cytotoxic activities. Compound 2i was the most potent compound with the IC50 values of 9 μMagainst Hela cells and 15 μMagainst Bel-7402 cells, respectively.
Synthesis & Pharmacological Evaluation of Ethyl 3-Substituted-phenyl-2-methylmercapto/ phenyl/ methyl-4(3H)-pyrimidone-5-carboxylates
Gupta, K. A.,Saxena, Anil K.,Jain, Padam C.
, p. 228 - 233 (2007/10/02)
A number of ethyl 3-substituted-phenyl-2-methylmercapto/ phenyl/ methyl-4(3H)-pyrimidone-5-carboxylates (V) have been prepared by the reaction of amidines (III) with diethyl ethoxymethylenemalonate.In order to confirm the structure (V), ethyl 3-(2'-methylphenyl)-2-methylmercapto-4(3H)pyrimidone-5-carboxylate (103) has been transformed into the earlier synthesised 3-(2'-methylphenyl)-2-methylmercapto-4(3H)-pyrimidone (115) by decarboxylation of 3-(2'-methylphenyl)-2-methylmercapto-4(3H)-pyrimidone-5-carboxylic acid (114), obtained by the alkaline hydrolysis of 103.Someof these compounds have shown antiinflammatory, diuretic and antipassive cutaneous anaphylaxis activities.
