149267-90-3

Upstream product

• 105-07-7 4-cyanobenzaldehyde 
• 870-46-2 t-butoxycarbonylhydrazine 
• 149267-91-4 tert-butyl-2-(4-cyanobenzylidene)hydrazinecarboxylate 

Downstream Products

• 386768-83-8 tert-butyl 2-(4-cyanobenzyl)-2-[(4-methyl-1-piperidinyl)carbonyl]hydrazine carboxylate 

Relevant academic research and scientific papers

Thrombin inhibitors built on an azaphenylalanine scaffold

A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin i

Novel thrombin inhibitors with azaphenylalanine scaffold

In this paper the synthesis and antithrombotic activity of a series of novel thrombin inhibitors with azaphenylalanine scaffold are described. By systematic structural modifications for this series we have identified optimal groups for achieving nanomolar potency, that led to potent inhibitors of thrombin with Ki values up to 11 nM.

Design and structure-activity relationship of thrombin inhibitors with an azaphenylalanine scaffold: Potency and selectivity enhancements via P2 optimization

Theoretical and structural studies followed by the directed synthesis and in vitro biological tests lead us to novel noncovalent thrombin pseudopeptide inhibitors. We have incorporated an azapeptide scaffold into the central part of the classical tripeptide D-Phe-Pro-Arg inhibitor structure thus eliminating one stereogenic center from the molecule. A series of compounds has been designed to optimize the occupancy of the S2 pocket of thrombin. Increased hydrophobicity at P2 provides an enhanced fit into this active site S2 pocket. In the present paper, we also report on the structure of these inhibitors in solution and conformational analysis of inhibitors in the active site in order to asses the consequences of the replacement of the central α-CH by a nitrogen functionality. In vitro biological testing of the designed inhibitors shows that elimination of R, S stereoisomerism and restriction of conformational freedom influences the binding of inhibitors in a favorable fashion.

Antiretroviral hydrazine derivatives

The invention relates to compounds of formula STR1 and salts, pharmaceutical compositions, intermediates and processes of preparation thereof.

Aza-peptide analogs as potent human immunodeficiency virus type-1 protease inhibitors with oral bioavailability

A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition- state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P2'P3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P3 and an ethyl carbamate in P3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED50 values 150-fold following oral application in mice.