645394-47-4

Usage

Chemical Properties

Red Oil

Uses

N-Arylaminonitriles as bioavailable peptidomimetic inhibitors of cathepsin B.

Upstream product

• 244778-26-5 N-tert-butyloxycarbonyl-O-benzyl serine nitrile 
• 23680-31-1 BOC-O-benzyl-L-serine 
• 66866-45-3 C₂₀H₂₉NO₇ 
• 620-05-3 iodomethylbenzene 
• 60656-87-3 benzyloxyacetoaldehyde 
• 143-33-9 sodium cyanide 
• 773837-37-9 sodium cyanide 
• 78331-03-0 N-(t-butoxycarbonyl)-L-(O-benzyl)serinamide 

Downstream Products

• 1093261-68-7 N-(2-(benzyloxy)-1-cyanoethyl)acetamide 
• 1093261-74-5 N-{1-cyano-2-[(phenylmethyl)oxy]ethyl}propanamide 
• 1093261-82-5 N-{1-cyano-2-[(phenylmethyl)oxy]ethyl}butanamide 

Relevant academic research and scientific papers

Rational design of potent non-nucleoside inhibitors of HIV-1 reverse transcriptase

A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50 1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.

New method for the synthesis of diversely functionalized imidazoles from N-acylated α-aminonitriles

(Equation presented) A new general method for the synthesis of medicinally important diversely functionalized imidazoles from N-acylated α-aminonitriles has been developed. N-Acylated α-aminonitriles were reacted with triphenylphosphine and carbon tetrahalide to afford 2,4-disubstituted 5-halo-1H-imidazoles in good yield. This new methodology was applied for the synthesis of 2-butyl-4-chloro-5-hydroxymethylimidazole. These halo-imidazoles can be directly converted to 2,4,5-trisubstituted imidazoles through palladium-catalyzed coupling reactions.

Process for preparing 2,4,5-trisubstituted imidazoles from N-acylated alpha-amino nitriles

The invention is a process for preparing an imidazole of formula I which comprises treating an N-acylated α-amino nitrile with a phosphine and a carbon tetrahalide of the formula CX4, wherein X is Cl or Br, to form a haloimidazole of the formula wherein R1 is selected from the group consisting of hydrogen, C1-6alkyl, —CH2-aryl, and aryl; and R2 is selected from the group consisting of hydrogen, C1-6alkyl, —CH2—O-aryl and aryl; and X is selected from the group consisting of Cl and Br.

Identification of dipeptidyl nitriles as potent and selective inhibitors of cathepsin B through structure-based drug design

Cathepsin B is a member of the papain superfamily of cysteine proteases and has been implicated in the pathology of numerous diseases, including arthritis and cancer. As part of an effort to identify potent, reversible inhibitors of this protease, we examined a series of dipeptidyl nitriles, starting with the previously reported Cbz-Phe-NH-CH2CN (19, IC50 = 62 μM). High-resolution X-ray crystallographic data and molecular modeling were used to optimize the P1, P2, and P3 substituents of this template. Cathepsin B is unique in its class in that it contains a carboxylate recognition site in the S2′ pocket of the active site. Inhibitor potency and selectivity were enhanced by tethering a carboxylate functionality from the carbon α to the nitrile to interact with this region of the enzyme. This resulted in the identification of compound 10, a 7 nM inhibitor of cathepsin B, with excellent selectivity over other cysteine cathepsins.