325850-28-0

Upstream product

• 2227-64-7 3'-nitro-2-bromoacetophenone 
• 103-85-5 monophenylthiourea 
• 92554-40-0 α-tosyloxy-m-nitroacetophenone 
• 121-89-1 3-Nitroacetophenone 
• 103-72-0 phenyl isothiocyanate 
• 62-53-3 aniline 

Relevant academic research and scientific papers

2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 2. Structure-Based Optimization and Investigation of Effects Specific to the Allosteric Mode of Action

Protein CK2 has gained much interest as an anticancer drug target in the past decade. We had previously described the identification of a new allosteric site on the catalytic α-subunit, along with first small molecule ligands based on the 4-(4-phenylthiazol-2-ylamino)benzoic acid scaffold. In the present work, structure optimizations guided by a binding model led to the identification of the lead compound 2-hydroxy-4-((4-(naphthalen-2-yl)thiazol-2-yl)amino)benzoic acid (27), showing a submicromolar potency against purified CK2α (IC50 = 0.6 μM). Furthermore, 27 induced apoptosis and cell death in 786-O renal cell carcinoma cells (EC50 = 5 μM) and inhibited STAT3 activation even more potently than the ATP-competitive drug candidate CX-4945 (EC50 of 1.6 μM vs 5.3 μM). Notably, the potencies of our allosteric ligands to inhibit CK2 varied depending on the individual substrate. Altogether, the novel allosteric pocket was proved a druggable site, offering an excellent perspective to develop efficient and selective allosteric CK2 inhibitors.

2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 1. Identification of an Allosteric Binding Site

CK2 is a ubiquitous Ser/Thr protein kinase involved in the control of various signaling pathways and is known to be constitutively active. In the present study, we identified aryl 2-aminothiazoles as a novel class of CK2 inhibitors, which displayed a non-ATP-competitive mode of action and stabilized an inactive conformation of CK2 in solution. Enzyme kinetics studies, STD NMR, circular dichroism spectroscopy, and native mass spectrometry experiments demonstrated that the compounds bind in an allosteric pocket outside the ATP-binding site. Our data, combined with molecular docking studies, strongly suggested that this new binding site was located at the interface between the αC helix and the flexible glycine-rich loop. A first hit optimization led to compound 7, exhibiting an IC50 of 3.4 μM against purified CK2α in combination with a favorable selectivity profile. Thus, we identified a novel class of CK2 inhibitors targeting an allosteric pocket, offering great potential for further optimization into anticancer drugs.

SUBSTITUTED HYDROPHOBIC BENZENE SULFONAMIDE THIAZOLE COMPOUNDS FOR USE IN TREATING CANCER

The present invention relates to compound of general formula (I) R1 is selected from H, aryl and alkyl, R2 is selected from H, alkyl, aryl and CO-R6; R3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR7, NR7R8, OR7 and SR7; R4 is selected from(C6-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl and (C6-C10) aryl, R5 represents H, R6, aryl, OH, OR6, O-aryl, SH, SR6, S-aryl, CN, NO2, CF3, COOR6, SO2NR6R7, CONR6R7, NH2, NHR6, NH-aryl, NR6R7, NHCOR6 or aminoacyl; R6 is alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH- alkyl or NH-di(alkyl); R7 and R8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.

Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells

We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates.

Effect of substituents on the regioselectivity of the reaction of α-tosyloxyketones with thioureas in acidic medium: Access to 2-aminothiazoles and 2-imino-2,3-dihydrothiazoles

Regioselective condensation of α-tosyloxyacetophenones 1 and N-substituted thioureas 2 in acidic medium to give regioisomers 2-aminothiazoles I and 2-imino-2,3-dihydrothiazoles II is largely influenced by the substituents present on 1 and 2. A mechanism,

Catalyst-free efficient synthesis of 2-aminothiazoles in water at ambient temperature

A highly efficient and facile method has been described for the synthesis of substituted 2-aminothiazoles in water without any added catalyst or co-organic solvent. The reaction was carried out at ambient temperature and the products were obtained in excellent isolated yields. The developed protocol is successfully applied for the preparation of an anti-inflammatory drug, fanetizole.