656-32-6Relevant articles and documents
Design, synthesis, and antipoliferative activities of novel substituted imidazole-thione linked benzotriazole derivatives
El-Malah, Afaf,Khayyat, Ahdab N.,Malebari, Azizah M.,Mohamed, Khaled O.
, (2021/10/12)
A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, BI9 showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC50 3.57, 0.40 and 2.63 μM, respectively. Compound BI9 was taken up for elaborate biological studies and the HL-60 cells in the cell cycle were arrested in G2/M phase. Compound BI9 showed remarkable inhibition of tubulin polymerization with the colchicine binding site of tubulin. In addition, compound BI9 promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2. These results provide guidance for further rational development of potent tubulin polymerization inhibitors for the treatment of cancer.
Convenient one-pot formation of highly functionalized 5-bromo-2-aminothiazoles, potential endocannabinoid hydrolase MAGL inhibitors
Prevost, Julien R.C.,Kozlova, Arina,Es Saadi, Bouazza,Yildiz, Esra,Modaffari, Sara,Lambert, Didier M.,Pochet, Lionel,Wouters, Johan,Dolu?ic?, Eduard,Frédérick, Rapha?l
supporting information, p. 4315 - 4319 (2018/11/03)
Highly functionalized 5-bromo-2-amino-1,3-thiazoles bearing various substituents could be easily prepared by a rapid and efficient one-pot method, using simple starting materials and mild conditions while avoiding the use of metal catalysts or inconvenient reagents such as elemental halogens. These useful products can serve as starting materials for other reactions or as pharmacologically interesting compounds. In our work we have shown that the resulting 5-bromothiazole compounds could lead to monoacylglycerol lipase (MAGL) inhibition in the μM range.
A novel one-pot synthesis of isothiocyanates and cyanamides from dithiocarbamate salts using environmentally benign reagent tetrapropylammonium tribromide
Kuotsu, Neivotsonuo Bernadette,Jamir, Latonglila,Phucho, Tovishe,Sinha, Upasana Bora
, p. 832 - 841 (2018/01/17)
A highly efficient and simple protocol for the synthesis of isothiocyanates and cyanamides from their respective amines in the presence of a mild, efficient, and non-toxic reagent tetrapropylammonium tribromide is described. High environmental acceptability of the reagents, cost effectiveness and high yields are the important attributes of this methodology.
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.
Facile synthesis, molecular docking and toxicity studies of 4-Phenyl-3-phenylamino-4H-[1,2,4]thiadiazol-5-one analogs as GABAA receptor agonists
Diwakar, Kirti,Sonar, Pankaj Kumar,Mishra, Mudita,Tripathi, Avinash C.,Saraf, Shailendra K.
, p. 2631 - 2642 (2016/10/25)
A series of 4-Phenyl-3-phenylamino-4H-[1,2,4]thiadiazol-5-one derivatives was synthesized by a simple method and their structures were established by physical and spectroscopic methods like infrared, mass and nuclear magnetic resonance spectroscopy. Elemental formulae of all the compounds were determined by elemental analysis and compared with the calculated value. Log P value and in vitro hydrolysis, in simulated gastric fluid and simulated intestinal fluid, for all the compounds were determined by standard methods. Synthesized 1, 2, 4-thiadiazolines were screened for their anticonvulsant activity against maximal electroshock method and isoniazid induced seizures. All the compounds showed good anticonvulsant activity. The compound 4-(3,4-dichloro-phenyl)-3-(3,4-dichloro-phenylamino)-4H-[1,2,4]thiadiazol-5-one (3a) was found to be the most potent member of the series. Molecular docking studies of the synthesized compounds depicted their stable ligand–receptor complex conformation with the typical binding pocket of γ-aminobutyric acid A receptor protein. Compound 3a confined its effect in the molecular docking studies also with non-covalent interactions with Tyr 157, Phe 200 and Tyr 205, the key interacting residues of γ-aminobutyric acid A receptor protein 4COF. In silico absorption, distribution, metabolism and elimination performance of all the compounds also appear to favour anticonvulsant effect. “LAZAR” and “OSIRIS” property explorer predicted nontoxic, nonmutagenic, noncarcinogenic, etc. nature for all the compounds. In conclusion, some γ-aminobutyric acid A receptor agonists have been synthesized in this study with promising drug-like properties, which merit further development.
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.
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.
Bromineless bromine as an efficient desulfurizing agent for the preparation of cyanamides and 2-aminothiazoles from dithiocarbamate salts
Yella, Ramesh,Kavala, Veerababurao,Patel, Bhisma K.
experimental part, p. 792 - 805 (2011/04/22)
In a one-pot procedure, bromineless brominating reagent 1,1'-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) has been used as a desulfurizing agent in the preparation of organic cyanamides and substituted thiazoles starting from dithiocarbamic acid salts. In this approach, alkyl/aryl isothiocyantes were first obtained by the desulfurization of dithiocarbamic acid salts with EDPBT. The in situ-generated isothiocyanates reacts with an aqueous ammonia, forming alkyl or aryl thioureas, which on subsequent oxidative desulfurization with EDPBT led to the formation of corresponding cyanamides in good yields. Alternatively, an efficient one-pot synthesis of substituted thiazoles has been achieved by the condensation of the in situ-generated 1-aryl thioureas with the in situ-generated -bromoketones from ketones, again using EDPBT. The reagent EDPBT can be easily prepared from the readily available reagents. Desulfurizing ability dominates over its brominating ability for substrates amenable to bromination.
Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1
Rist, ystein,Grimstrup, Marie,Receveur, Jean-Marie,Frimurer, Thomas M.,Ulven, Trond,Kostenis, Evi,Hoegberg, Thomas
scheme or table, p. 1177 - 1180 (2010/06/15)
Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP).
A one-pot preparation of cyanamide from dithiocarbamate using molecular iodine
Nath, Jayashree,Patel, Bhisma K.,Jamir, Latonglila,Sinha, Upasana Bora,Satyanarayana
experimental part, p. 1503 - 1506 (2010/05/18)
An efficient one-pot method for the synthesis of cyanamides from dithiocarbamate salts via a double desulfurization strategy using molecular iodine is disclosed. Dithiocarbamates, by the action of iodine yield isothiocyanates in situ, which on treatment with aqueous NH3 give thioureas. The thioureas so generated undergo further oxidative desulfurization with I2 giving corresponding cyanamides in good yields. Environmental benignity, cost effectiveness and high yields are the important attributes of this one pot procedure. The Royal Society of Chemistry 2009.
