408365-95-7

Upstream product

• 82548-78-5 ethyl {2-[(tert-butoxycarbonyl)amino]-1,3-thiazol-4-yl}acetate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 53266-94-7 ethyl 2-amino-1,3-thiazol-4-acetate 
• 147284-02-4 tert-butyl 4-(2-hydroxyethyl)-1,3-thiazol-2-ylcarbamate 
• 98-59-9 p-toluenesulfonyl chloride 

Downstream Products

• 408365-96-8 tert-butyl 4-{2-(4-({[4'-(trifluoromethyl)-1,1'-biphenyl-2-yl]carbonyl}amino)phenoxy]ethyl}-1,3-thiazol-2-ylcarbamate 
• 1357621-27-2 N-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-N'-{4-[2-(3-pyridinylmethoxy)ethyl]-1,3-thiazol-2-yl}urea 
• 215099-32-4 tert-butyl 4-(2-aminoethyl)-1,3-thiazol-2-ylcarbamate 

Relevant academic research and scientific papers

Synthesis and Evaluation of Bifunctional Aminothiazoles as Antiretrovirals Targeting the HIV-1 Nucleocapsid Protein

Small molecule inhibitors of the HIV-1 nucleocapsid protein (NC) are considered as promising agents in the treatment of HIV/AIDS. In an effort to exploit the privileged 2-amino-4-phenylthiazole moiety in NC inhibition, here we conceived, synthesized, and tested in vitro 18 NC inhibitors (NCIs) bearing a double functionalization. In these NCIs, one part of the molecule is deputed to interact noncovalently with the NC hydrophobic pocket, while the second portion is designed to interact with the N-terminal domain of NC. This binding hypothesis was verified by molecular dynamics simulations, while the linkage between these two pharmacophores was found to enhance antiretroviral activity both on the wild-type virus and on HIV-1 strains with resistance to currently licensed drugs. The two most interesting compounds 6 and 13 showed no cytotoxicity, thus becoming valuable leads for further investigations.

Structure-based design, synthesis and biological evaluation of N-pyrazole, N′-thiazole urea inhibitors of MAP kinase p38α

In this paper, we present the structure-based design, synthesis and biological activity of N-pyrazole, N′-thiazole-ureas as potent inhibitors of p38α mitogen-activated protein kinase (p38α MAPK). Guided by complex crystal structures, we employed the initially identified N-aryl, N′-thiazole urea scaffold and introduced key structural elements that allowed the formation of novel hydrogen bonding interactions within the allosteric site of p38α, resulting in potent type III inhibitors. [4-(3-tert-Butyl-5-{[(1,3-thiazol-2-ylamino)carbonyl]amino}-1H-pyrazol-1-yl) -phenyl]acetic acid 18c was found to be the most potent compound within this series and inhibited p38α activity with an IC50 of 135 ± 21 nM. Its closest analog, ethyl [4-(3-tert-butyl-5-{[(1,3-thiazol-2-ylamino) carbonyl]amino}-1H-pyrazol-1-yl)phenyl]acetate 18b, effectively inhibited p38α mediated phosphorylation of the mitogen activated protein kinase activated protein kinase 2 (MK2) in HeLa cells.