775273-10-4

Basic information

• Product Name: (S)-1-((R)-2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-cyano-thiazol-2-ylmethyl)-amide
• Synonyms: (S)-1-((R)-2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-cyano-thiazol-2-ylmethyl)-amide
• CAS NO: 775273-10-4
• Molecular Weight: 459.572
• Mol File: 775273-10-4.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: (S)-1-((R)-2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-cyano-thiazol-2-ylmethyl)-amide(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1-((R)-2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-cyano-thiazol-2-ylmethyl)-amide(775273-10-4)
• EPA Substance Registry System: (S)-1-((R)-2-Amino-3,3-diphenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-cyano-thiazol-2-ylmethyl)-amide(775273-10-4)

Safety Data

• Hazardous Substances Data: 775273-10-4(Hazardous Substances Data)

Upstream product

• 71904-80-8 2-((tert-butoxycarbonylamino)methyl)thiazole-4-carboxylic acid 
• 182120-82-7 2-(tert-butoxycarbonylaminomethyl)-1,3-thiazole-4-carboxamide 
• 251294-64-1 2-[N-(tert-butoxycarbonyl)aminomethyl]thiazole-4-carbonitrile 

Relevant articles and documents

Efficacious and orally bioavailable thrombin inhibitors based on a 2,5-thienylamidine at the P1 position: Discovery of N-carboxymethyl-D-diphenylalanyl-L-prolyl[(5-amidino-2- thienyl)methyllamide

Thrombin, a crucial enzyme in the blood coagulation, has been a target for antithrombotic therapy. Orally active thrombin inhibitors would provide effective and safe prophylaxis for venous and arterial thrombosis. We conducted optimization of a highly efficacious benzamidine-based thrombin inhibitor LB30812 (3, Ki = 3 pM) to improve oral bioavailability. Of a variety of arylamidines investigated at the P1 position, 2,5-thienylamidine effectively replaced the benzamidine without compromising the thrombin inhibitory potency and oral absorption. The sulfamide and sulfonamide derivatization at the N-terminal position in general afforded highly potent thrombin inhibitors but with moderate oral absorption, while the well-absorbable N-carbamate derivatives exhibited limited metabolic stability in S9 fractions. The present work culminated in the discovery of the N-carboxymethyl- and 2,5-thienylamidine-containing compound 22 that exhibits the most favorable profiles of anticoagulant and antithrombotic activities as well as oral bioavilability (Ki = 15 pM; F = 43%, 42%, and 15% in rats, dogs, and monkeys, respectively). This compound on a gravimetric basis was shown to be more effective than a low molecular weight heparin, enoxaparin, in the venous thrombosis models of rat and rabbit. Compound 22 (LB30870) was therefore selected for further preclinical and clinical development.