21381-67-9Relevant academic research and scientific papers
Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies
Anbar, Hanan S.,El-Gamal, Mohammed I.,Jeon, Hong R.,Kwon, Dow,Lee, Bong S.,Oh, Chang-Hyun,Tarazi, Hamadeh
, p. 1712 - 1726 (2020/10/02)
A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound 1zb is the most potent agains
Design and synthesis of novel pyrrolo[2,3-b]pyridine derivatives targeting V600EBRAF
Abdel-Maksoud, Mohammed S.,Ali, Eslam M. H.,Ammar, Usama M.,Mersal, Karim I.,Oh, Chang-Hyun,Yoo, Kyung Ho
, (2020/04/28)
Several pyrrolo[2,3-b]pyridine-based B-RAF inhibitors are well known and some of them are currently FDA approved as anticancer agents. Based on the structure of these FDA approved V600EB-RAF inhibitors, two series of pyrrolo[2,3-b]pyridine scaffold were designed and synthesized in attempt to develop new potent V600EB-RAF inhibitors. The 38 synthesized compounds were biologically evaluated for their V600EB-RAF inhibitory effect at single dose (10 μM). Compounds with high percent inhibition were tested to determine their IC50 over V600EB-RAF. Compounds 34e and 35 showed the highest inhibitory effect with IC50 values of 0.085 μM and 0.080 μM, respectively. Headed for excessive biological evaluation, the synthesized derivatives were tested over sixty diverse human cancer cell lines. Only compound 35 emerged as a potent cytotoxic agent against different panel of human cancer cell lines.
Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety
Pan, Xiaoyan,Liang, Liyuan,Sun, Ying,Si, Ru,Zhang, Qingqing,Wang, Jin,Fu, Jia,Zhang, Junjie,Zhang, Jie
, p. 232 - 242 (2019/06/14)
As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-AblWT and Bcr-AblT315I in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-AblWT and Bcr-AblT315I kinases with IC50 of 0.043 μM and 0.17 μM, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 μM and 5.42 μM, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization.
Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold
Abdel-Maksoud, Mohammed S.,Ammar, Usama M.,Oh, Chang-Hyun
, p. 2041 - 2051 (2019/04/05)
In this work, a new series of imidazo[2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo[2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. In addition, IC50s of the target compounds were determined over A375 and SK-MEL-28 cell lines using sorafenib as positive control. Compounds12b, 12c, 12e, 12f, 15a, 15d, 15f, 14g and 15h exhibited superior activity when compared to sorafenib. The most potent compounds were tested against wild type BRAF, v600e BRAF, and CRAF. Compound 15h exhibited a potential inhibitory effect againstV600EBRAF (IC50 = 9.3 nM).
Investigation of synergistic antimicrobial effects of the drug combinations of meropenem and 1,2-benzisoselenazol-3(2H)-one derivatives on carbapenem-resistant Enterobacteriaceae producing NDM-1
Jin, Wen Bin,Xu, Chen,Cheng, Qipeng,Qi, Xiao Lin,Gao, Wei,Zheng, Zhiwei,Chan, Edward W.C.,Leung, Yun-Chung,Chan, Tak Hang,Wong, Kwok-Yin,Chen, Sheng,Chan, Kin-Fai
, p. 285 - 302 (2018/07/13)
The worldwide prevalence of NDM-1-producing bacteria has drastically undermined the clinical efficacy of the last line antibiotic of carbapenems, prompting a need to devise effective strategy to preserve their clinical value. Our previous studies have shown that ebselen can restore the efficacy of meropenem against a laboratory strain that produces NDM-1. Here we report the construction of a focused compound library of 1,2-benzisoselenazol-3(2H)-one derivatives which comprise a total of forty-six candidate compounds. The structure-activity relationship of these compounds and their potential to serve as an adjuvant to enhance the antimicrobial efficacy of meropenem against a collection of clinical NDM-1-producing carbapenem-resistant Enterobacteriaceae isolates was examined. Drug combination assays indicated that these derivatives exhibited synergistic antimicrobial activity when used along with meropenem, effectively restoring the activity of carbapenems against the resistant strains tested in a Galleria mellonella larvae in vivo infection model. The mode of inhibition of one compound, namely 11_a38, which was depicted when tested on the purified NDM-1 enzyme, indicated that it could covalently bind to the enzyme and displaced one zinc ion from the active site. Overall, this study provides a novel 1,2-benzisoselenazol-3(2H)-one scaffold that exhibits strong synergistic antimicrobial activity with carbapenems, and low cytotoxicity. The prospect of application of such compounds as carbapenem adjuvants warrants further evaluation.
The α-effect in hydrazinolysis of 4-chloro-2-nitrophenyl x-substituted-benzoates: Effect of substituent x on reaction mechanism and the α-effect
Kim, Min-Young,Kim, Tae-Eun,Lee, Jieun,Um, Ik-Hwan
, p. 2271 - 2276 (2014/09/29)
Second-order rate constants (kN) have been measured spectrophotometrically for the reaction of 4-chloro-2- nitrophenyl X-substituted-benzoates (6a-6h) with a series of primary amines including hydrazine in 80 mol % H2O/20 mol % DMSO at 25.0°C. The Bronsted-type plot for the reaction of 4-chloro-2-nitrophenyl benzoate (6d) is linear with βnuc = 0.74 when hydrazine is excluded from the correlation. Such a linear Bronsted-type plot is typical for reactions reported previously to proceed through a stepwise mechanism in which expulsion of the leaving group occurs in the rate-determining step (RDS). The Hammett plots for the reactions of 6a-6h with hydrazine and glycylglycine are nonlinear. In contrast, the Yukawa-Tsuno plots exhibit excellent linear correlations with ?X = 1.29-1.45 and r = 0.53-0.56, indicating that the nonlinear Hammett plots are not due to a change in RDS but are caused by resonance stabilization of the substrates possessing an electron-donating group (EDG). Hydrazine is ca. 47-93 times more reactive than similarly basic glycylglycine toward 6a-6h (e.g., the α-effect). The α-effect increases as the substituent X in the benzoyl moiety becomes a stronger electronwithdrawing group (EWG), indicating that destabilization of the ground state (GS) of hydrazine through the repulsion between the nonbonding electron pairs on the two N atoms is not solely responsible for the substituent-dependent α-effect. Stabilization of transition state (TS) through five-membered cyclic TSs, which would increase the electrophilicity of the reaction center or the nucleofugality of the leaving group, contributes to the α-effect observed in this study.
Highly diastereo- and enantioselective direct Barbas-List aldol reactions promoted by novel benzamidoethyl and benzamidopropyl prolinamides in water
Pedrosa, Rafael,Andres, Jose M.,Manzano, Ruben,Roman, David,Tellez, Silvia
supporting information; experimental part, p. 935 - 940 (2011/03/22)
Four novel benzamido-functionalized prolinamides have been prepared and tested as organocatalysts for enantioselective aldol reaction of aldehydes and cyclic ketones in water. In particular, prolinamide derived from achiral ethylene diamine was the best c
Synthesis of new 6-(4-Fluorophenyl)-5-(2-substituted pyrimidin-4-yl) imidazo[2,1-b] thiazole derivatives and their antiproliferative activity against melanoma cell line
Park, Jin-Hun,Oh, Chang-Hyun
experimental part, p. 2854 - 2860 (2012/04/17)
Synthesis of a new series of pyrimidinyl-imidazo[2,1-b]thiazole derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the pyrimidinyl ring side chain was investigated.
L-prolinamides derived from chiral and achiral 1,2-diamines as useful bifunctional organocatalysts for direct diastereo-and enantioselective aldol reaction
Pedrosa, Rafael,Andres, Jose M.,Manzano, Ruben,Rodriguez, Paula
experimental part, p. 5310 - 5319 (2010/11/17)
Diastereomeric catalysts 5 and epi-5, which differ in the configuration of the stereocenter at the amino component, have been prepared from L-proline and (S)-N2,N2-dibenzyl-3-methylbutane-1,2-diamine or (R)-N1,N1/sup
