63494-72-4

Upstream product

• 98-88-4 benzoyl chloride 
• 65-85-0 benzoic acid 
• 532-55-8 Benzoyl isothiocyanate 
• 88-17-5 2-(trifluoromethyl)benzenamine 

Downstream Products

• 82636-24-6 2-Methylsulfanyl-6-oxo-1-(2-trifluoromethyl-phenyl)-1,6-dihydro-pyrimidine-5-carboxylic acid ethyl ester 
• 82635-96-9 2-[2-Methyl-3-(2-trifluoromethyl-phenyl)-isothioureidomethylene]-malonic acid diethyl ester 
• 57513-63-0 N-(2-trifluormethylphenyl)-S-methylisothiourea 
• 1391724-88-1 C₁₇H₁₅F₃N₂O₂S₂ 
• 1391724-87-0 C₂₀H₁₅F₃N₂O₂S₂ 
• 1391724-86-9 C₁₆H₁₂F₄N₂O₂S₂ 
• 1391724-85-8 C₂₅H₃₁F₃N₂O₂S₂ 
• 1391724-84-7 C₁₆H₁₁Cl₂F₃N₂O₂S₂ 
• 1391724-83-6 C₁₆H₁₂F₃N₃O₄S₂ 

Relevant academic research and scientific papers

Search for the Active Ingredients from a 2-Aminothiazole DMSO Stock Solution with Antimalarial Activity

Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme PfIspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from. Solvent- and temperature-dependent studies using HRMS and NMR spectroscopy to monitor the decomposition led to the isolation and in vitro evaluation of several fractions against PfIspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised compounds using SFC purification and correlated the observed activities to them. Due to the unstable nature of the two isolates, it is likely that they undergo further decomposition contributing to the overall instability of the compound.

Development of an Improved Guanidine-Based Rac1 Inhibitor with in vivo Activity against Non-Small Cell Lung Cancer

The Rho GTPase Rac1 is involved in the control of cytoskeleton reorganization and other fundamental cellular functions. Aberrant activity of Rac1 and its regulators is common in human cancer. In particular, deregulated expression/activity of Rac GEFs, res

Mononuclear copper(I) complexes with triphenylphosphine and N,N′-disubstituted thioureas: synthesis, characterization, and biological evaluation

Twelve new complexes, of the general formula CuCl(TPP)2Tu1–12 (Tu = thiourea), were synthesized by the reaction of CuCl(TPP)3 (TPP = triphenylphosphine) and various N,N′-disubstituted thioureas. The structures of the synthesized complexes were characterized by different techniques such as Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy (1H, 13C, 31P, and 19F), and the representative complexes (1, 2 and 12) were analyzed via single crystal X-ray diffraction. The single crystal X-ray analysis revealed that copper(I) is coordinated with chlorine, two TPP, and the thiourea ligands through the sulfur atom in a mononuclear distorted tetrahedral mode. The compounds were tested for antibacterial, antifungal, cytotoxicity, antileishmanial, and antioxidant activities. The results showed that the synthesized complexes are significantly more active than the free ligands and the commercial reference compounds. The high biological activities of the complexes versus free ligands can be attributed to the copper(I) chloride complexation with thiourea ligands. The synthesized complexes were also evaluated, both experimentally and theoretically, for DNA binding studies. The UV-visible spectroscopic and molecular docking studies demonstrated that the complexes are conjugating with DNA through a groove binding mode.

Discovery of Novel Thiazol-2-Amines and Their Analogues as Bioactive Molecules: Design, Synthesis, Docking and Biological Evaluation

A simple and highly efficient procedure for the synthesis of novel thiazol-2-amines, via Mannich reaction with secondary amines, is described. The newly synthesized derivatives 8(a-e) and 9(a-e) were characterized by 1 H NMR, 13 C NMR, IR, Mass spectroscopy and elemental analysis. All the derivatives were evaluated for their in-vitro anti-microbial activity against a panel of pathogenic strains of bacteria and fungi. The SAR showed that the secondary amines had a significant impact on the in-vitro antimicrobial activity of this class of agents. The most potent analogue N-((1H-benzo[d]imidazol-1-yl)methyl)-N-(2(trifluoromethyl)phenyl)-4,5-dihydrothiazol-2-amine (8c) showed excellent inhibition with MIC (zoi) 6.25 (22.5), 25 (21.5) and 25 (18) μg/mL against E. coli, S. typhi and P. aeruginosa respectively as compared to the standard drug. Molecular docking results suggest that compound exhibited inhibitory activity by binding of the title compound within the active sites of the inhibiting Enoyl ACP reductase, Lipid A, Pyridoxal kinase and type I DHQase enzymes. The compound exhibited promising anti-microbial activity which can be further explored as potential lead for the development of cheaper, safe, effective and potent drugs against resistant microbial parasites.

Synergism of fused bicyclic 2-aminothiazolyl compounds with polymyxin B against: Klebsiella pneumoniae

A series of fused bicyclic 2-aminothiazolyl compounds were synthesized and evaluated for their synergistic effects with polymyxin B (PB) against Klebsiella pneumoniae (SIPI-KPN-1712). Some of the synthesized compounds exhibited synergistic activity. When 4 μg ml-1 compound B1 was combined with PB, it showed potent antibacterial activity, achieving 64-fold reduction of the MIC of PB. Furthermore, compound B1 showed prominent synergistic efficacy in both concentration gradient and time-kill curves in vitro. In addition, B1 combined with PB also exhibited synergistic and partial synergistic effect against E. coli (ATCC25922 and its clinical isolates), Acinetobacter baumannii (ATCC19606 and its clinical isolates), and Pseudomonas aeruginosa (Pae-1399).

Solution-phase microwave assisted parallel synthesis of N,N′-disubstituted thioureas derived from benzoic acid: Biological evaluation and molecular docking studies

An efficient and facile microwave-assisted solution phase parallel synthesis for a 26-member library of N,N′-disubstituted thiourea analogs were accomplished successfully. The reaction time for synthesis of analogs was drastically reduced from a reported 8-12 h to only 10 min. Compounds were more than 95% pure, as characterized by modern analytical techniques, i.e. 1H & 13C NMR and FT-IR. The solid phase structural analysis has also been performed by single crystal XRD analysis. Synthesized compounds were preliminary screened for their in vitro urease inhibition and antifungal activity. Most of the compounds were found to be potent inhibitors of urease. However, the most significant activity was found for 11 with IC 50 of 1.67 μM. The docking scores correlate with the IC 50 values of inhibitors.

Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis

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 biological evaluation of substituted 4-arylthiazol-2-amino derivatives as potent growth inhibitors of replicating Mycobacterium tuberculosis H37RV

In search of potential therapeutics for tuberculosis, we describe herein synthesis and biological evaluation of some substituted 4-arylthiazol-2-amino derivatives as modified analogues of the antiprotozoal drug Nitazoxanide (NTZ), which has recently been reported as potent inhibitor of Mtb H37Rv (Mtb MIC = 52.12 μM) with an excellent ability to evade resistance. Among the synthesized derivatives, the two compounds 7a (MIC = 15.28 μM) and 7c (MIC = 17.03 μM) have exhibited about three times better Mtb growth inhibitory activity over NTZ and are free from any cytotoxicity (Vero CC50 of 244 and 300 μM respectively). These two compounds represent promising leads for further optimization.

Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents

A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters (F, σ or μ) having high statistical significance > 99.9% (F2,22 > 15.0; F2,22α:0.001 = 11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.