182005-26-1

Basic information

• Product Name: (R)-2-benzyloxycarbonylamino-5-hydroxypentanoic acid methyl ester
• Synonyms: (R)-2-benzyloxycarbonylamino-5-hydroxypentanoic acid methyl ester
• CAS NO: 182005-26-1
• Molecular Weight: 281.309
• Mol File: 182005-26-1.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: (R)-2-benzyloxycarbonylamino-5-hydroxypentanoic acid methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-benzyloxycarbonylamino-5-hydroxypentanoic acid methyl ester(182005-26-1)
• EPA Substance Registry System: (R)-2-benzyloxycarbonylamino-5-hydroxypentanoic acid methyl ester(182005-26-1)

Safety Data

• Hazardous Substances Data: 182005-26-1(Hazardous Substances Data)

Upstream product

• 26566-11-0 N-(benzyloxycarbonyl)-D-glutamic acid 1-methyl ester 
• 97975-57-0 (4R)-4-(2-Carboxyethyl)-3-[(phenylmethoxy)carbonyl]oxazolidin-5-one 
• 67-56-1 methanol 
• 716349-66-5 (R)-4-(3-Hydroxy-propyl)-5-oxo-oxazolidine-3-carboxylic acid benzyl ester 

Downstream Products

• 182005-31-8 (R)-2-Benzyloxycarbonylamino-5-bromo-pentanoic acid methyl ester 
• 1159502-82-5 (R)-2-benzyloxycarbonylamino-5-iodopentanoic acid methyl ester 
• 1159502-83-6 (R)-2-benzyloxycarbonylamino-5-(diethoxy-phosphoryl)-pentanoic acid methyl ester 
• 1159502-84-7 (R)-2-benzyloxycarbonylamino-5-(diethoxy-phosphoryl)-pentanoic acid 
• 182210-00-0 methyl (2R)-(benzyloxycarbonyl)pyrrolidine-2-carboxylate 

Relevant articles and documents

4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel

Recent post hoc analyses of several clinical trials with P2Y12 antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y12 antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.

PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS

The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

Stereoselective synthesis of the cis-275B decahydroquinoline ring system

The Diels-Alder precursor was constructed from readily available D-glutamic acid utilizing a series of functional group transformations. The stereocenter of the amino acid provided the desired stereochemistry at C2 and diastereoselectively directed the in