632333-33-6

Basic information

• Product Name: 2-Oxazolidinone, 3-[(2R)-2-(hydroxymethyl)-4-methyl-1-oxopentyl]-4-(phenylmethyl)-, (4S)-
• CAS NO: 632333-33-6
• Molecular Formula: C17H23NO4
• Molecular Weight: 305.374
• Mol File: 632333-33-6.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 2-Oxazolidinone, 3-[(2R)-2-(hydroxymethyl)-4-methyl-1-oxopentyl]-4-(phenylmethyl)-, (4S)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Oxazolidinone, 3-[(2R)-2-(hydroxymethyl)-4-methyl-1-oxopentyl]-4-(phenylmethyl)-, (4S)-(632333-33-6)
• EPA Substance Registry System: 2-Oxazolidinone, 3-[(2R)-2-(hydroxymethyl)-4-methyl-1-oxopentyl]-4-(phenylmethyl)-, (4S)-(632333-33-6)

Safety Data

• Hazardous Substances Data: 632333-33-6(Hazardous Substances Data)

Upstream product

• 38136-29-7 4-methylvaleroyl chloride 
• 646-07-1 4-Methylpentanoic acid 
• 110-88-3 1,3,5-Trioxan 
• 113543-30-9 (S)-4-benzyl-3-(4-methylpentanoyl)oxazolidin-2-one 

Relevant articles and documents

Discovery of TD-0212, an Orally Active Dual Pharmacology AT1 Antagonist and Neprilysin Inhibitor (ARNI)

Dual inhibition of angiotensin-converting enzyme (ACE) and neprilysin (NEP) by drugs such as omapatrilat produces superior antihypertensive efficacy relative to ACE inhibitors but is associated with a higher risk of life-threatening angioedema due to bradykinin elevations. We hypothesized that dual AT1 (angiotensin II type 1 receptor) blockade and NEP inhibition with a single molecule would produce similar antihypertensive efficacy to omapatrilat without the risk of angioedema since ACE (the rate limiting enzyme in bradykinin metabolism) would remain uninhibited. Merging the structures of losartan (an AT1 antagonist) and thiorphan (a NEP inhibitor) led to the discovery of a novel series of orally active, dual AT1 antagonist/NEP inhibitors (ARNIs) exemplified by compound 35 (TD-0212). In models of renin-dependent and -independent hypertension, 35 produced blood pressure reductions similar to omapatrilat and combinations of AT1 receptor antagonists and NEP inhibitors. Upper airway angioedema risk was assessed in a rat tracheal plasma extravasation (TPE) model. Unlike omapatrilat, 35 did not increase TPE at antihypertensive doses. Compound 35 therefore provides the enhanced activity of dual AT1/NEP inhibition with a potentially lower risk of angioedema relative to dual ACE/NEP inhibition.

Dual-acting antihypertensive agents

The invention is directed to compounds having the formula: wherein: Ar, r, Y, Z, Q, W, X, and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.