154248-99-4

Basic information

• Product Name: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester
• Synonyms: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester;N-[[Methyl[[2-(1-methylethyl)-4-thiazolyl]methyl]amino]carbonyl]-L-valine methyl ester
• CAS NO: 154248-99-4
• Molecular Formula: C₁₅H₂₅N₃O₃S
• Molecular Weight: 327.44
• Product Categories: Amino Acids 13C, 2H, 15N;Amino Acids & Derivatives;Heterocycles;Intermediates
• Mol File: 154248-99-4.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 490.86 °C at 760 mmHg
• Flash Point: 250.664 °C
• Appearance: /
• Density: 1.136
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.523
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 12.22±0.46(Predicted)
• CAS DataBase Reference: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester(154248-99-4)
• EPA Substance Registry System: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester(154248-99-4)

Safety Data

• Hazardous Substances Data: 154248-99-4(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

Different sources of media describe the Uses of 154248-99-4 differently. You can refer to the following data:
1. An intermediate in the synthesis of Ritonavir.
2. An intermediate in the synthesis of Ritonavir

InChI:InChI=1/C15H25N3O3S/c1-9(2)12(14(19)21-6)17-15(20)18(5)7-11-8-22-13(16-11)10(3)4/h8-10,12H,7H2,1-6H3,(H,17,20)/t12-/m0/s1

Upstream product

• 154212-60-9 N-methyl-N-<(2-isopropyl-4-thiazolyl)methyl>amine 
• 162537-10-2 N-<<(4-nitrophenyl)oxy>carbonyl>-L-valine methyl ester 
• 908591-25-3 2-isopropyl-4-(((N-methyl)amino)methyl)thiazole hydrochloride 
• 4070-48-8 L-Valine methyl ester 
• 6306-52-1 L-valine methylester hydrochloride 
• 126147-70-4 (2S)-3-Methyl-2-(phenoxycarbonyl)aminobutyric acid 
• 65386-28-9 4-(Chloromethyl)-2-isopropylthiazole Hydrochloride 

Downstream Products

• 154212-61-0 N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valine 
• 1551453-85-0 C₃₇H₄₈N₆O₄S₂ 
• 1551453-99-6 C₂₉H₄₁N₇O₄S₂ 
• 1551454-03-5 C₃₆H₄₇N₇O₄S₂ 
• 1551455-44-7 C₂₅H₃₆N₄O₄S 
• 1551455-46-9 C₂₄H₃₄N₄O₃S 
• 155213-67-5 ritonavir 

Relevant articles and documents

Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350)

The HIV protease inhibitor (PI) ritonavir (RTV) has been widely used as a pharmacoenhancer for other PIs, which are substrates of cytochrome P450 3A (CYP3A). However the potent anti-HIV activity of ritonavir may limit its use as a pharmacoenhancer with other classes of anti-HIV agents. Ritonavir is also associated with limitations such as poor physicochemical properties. To address these issues a series of compounds with replacements at the P2 and/or P3 region was designed and evaluated as novel CYP3A inhibitors. Through these efforts, a potent and selective inhibitor of CYP3A, GS-9350 (cobicistat) with improved physiochemical properties was discovered.

MODULATORS OF PHARMACOKINETIC PROPERTIES OF THERAPEUTICS

The present application provides for a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy

The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption. Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 μM) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.