1259946-99-0

Upstream product

• 55696-50-9 tert-butyl 4-cyanobenzoate 
• 6068-72-0 4-cyanobenzoyl chlorIde 
• 619-65-8 4-cyanobenzoic Acid 
• 1259946-96-7 4-[(2-thiophenecarbonyl)oxyamidino]benzoic acid tert-butyl ester 
• 184576-27-0 C₁₂H₁₆N₂O₃ 

Downstream Products

• 1259945-99-7 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}-leucyl-glycine-nitrile 
• 1259946-00-3 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}-N-methylleucyl-glycine-nitrile 
• 1259947-22-2 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}-leucine 1,2-dimethylhydrazide 
• 1259947-24-4 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}-N-methylleucine 1,2-dimethylhydrazide 
• 1259946-02-5 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}-leucyl-methylazaalanine-nitrile 
• 1259946-06-9 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}-N-methylleucyl-methylazaalanine-nitrile 
• 1346933-18-3 N-{4-[5-(2-thienyl)-1,2,4-oxadiazol-3-yl]benzoyl}homocycloleucyl-glycine-nitrile 

Relevant academic research and scientific papers

Synthesis of benzoic acids containing a 1,2,4-oxadiazole ring

A new approach to the synthesis of 4and 3-(5-R-1,2,4-oxadiazol-3-yl)benzoic acids via a selective oxidation of 5-R-3-tolyl-1,2,4-oxadiazoles with air oxygen in the presence of a catalytic system based on cobalt acetate was suggested. This synthesis allowed us to obtain the products in higher yields and with shorter sequence of steps as compared to the known procedures.

Active Site Mapping of Human CathepsinF with Dipeptide Nitrile Inhibitors

Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex classII. CathepsinS is the major processing enzyme of the invariant chain, but cathepsinF acts in macrophages as its functional synergist which is as potent as cathepsinS in invariant chain cleavage. Dedicated low-molecular-weight inhibitors for cathepsinF have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent-reversible inhibitors, was performed to draw structure-activity relationships for the non-primed binding region of human cathepsinF. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsinsF, B, L, K and S. Compounds 10 (N-(4-phenylbenzoyl)-leucylglycine nitrile) and 12 (N-(4-phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsinF, with Ki values 10nM. With all dipeptide nitriles from our study, a 3D activity landscape was generated to visualize structure-activity relationships for this series of cathepsinF inhibitors. Mapping with nitriles: For human cathepsinF, low-molecular-weight inhibitors have not been developed so far. Therefore, a library of 52 dipeptide nitriles, known to interact in a covalent but reversible manner with the active site cysteine, was evaluated for cathepsinF inhibition. With the kinetic data in hand, optimized candidates were designed, synthesized, and tested to improve the activity profile as cathepsinF inhibitors.

Structural optimization of azadipeptide nitriles strongly increases association rates and allows the development of selective cathepsin inhibitors

Using the example of cathepsin K, we demonstrate the design of highly potent and selective azadipeptide nitrile inhibitors. A systematic scan with respect to P2 and P3 substituents was carried out. Structural modifications strongly affected the enzyme-inh