205754-32-1

Basic information

• Product Name: rac 8-Hydroxy Efavirenz
• Synonyms: 6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-8-hydroxy-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one
• CAS NO: 205754-32-1
• Molecular Formula: C14H9ClF3NO3
• Molecular Weight: 331.67
• Product Categories: Anti-viral Compounds;Anti-virals;Inhibitors;Intermediates & Fine Chemicals;Metabolites;Non-nucleoside Reverse Transcriptase;Pharmaceuticals
• Mol File: 205754-32-1.mol
• Article Data: 7

Chemical Properties

• Melting Point: 186-188?C
• Boiling Point: 373.6°C at 760 mmHg
• Flash Point: 179.7°C
• Appearance: /
• Density: 1.64g/cm³
• Vapor Pressure: 4.13E-06mmHg at 25°C
• Refractive Index: 1.608
• Storage Temp.: -20°C Freezer
• CAS DataBase Reference: rac 8-Hydroxy Efavirenz(CAS DataBase Reference)
• NIST Chemistry Reference: rac 8-Hydroxy Efavirenz(205754-32-1)
• EPA Substance Registry System: rac 8-Hydroxy Efavirenz(205754-32-1)

Safety Data

• Hazardous Substances Data: 205754-32-1(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Solid

Uses

Different sources of media describe the Uses of 205754-32-1 differently. You can refer to the following data:
1. A metabolite of Efavirenz, a nonnucleoside HIV-1 reverse transcriptase inhibitor
2. A metabolite of Efavirenz (E425000), a nonnucleoside HIV-1 reverse transcriptase inhibitor.

InChI:InChI=1/C14H9ClF3NO3/c15-8-5-9-11(10(20)6-8)19-12(21)22-13(9,14(16,17)18)4-3-7-1-2-7/h5-7,20H,1-2H2,(H,19,21)/t13-/m0/s1

Upstream product

• 154598-52-4 efavirenz 
• 75-44-5 phosgene 
• 429-41-4 tetrabutyl ammonium fluoride 
• 205756-25-8 2-(2-Amino-5-chloro-3-(t-butyldimethylsilyloxy)-phenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol 
• 205756-24-7 2'-amino-5'-chloro-3'-(t-butyldimethylsilyloxy)-2,2,2-trifluoroacetophenone 
• 205756-23-6 2'-amino-5'-chloro-3'-hydroxy-2,2,2-trifluoroacetophenone 
• 205756-22-5 2'-amino-5'-chloro-3'-methoxy-2,2,2-trifluoroacetophenone 
• 113137-29-4 N-(4-chloro-2-methoxyphenyl)-2,2-dimethylpropanamide 
• 93-50-5 4-chloro-o-anisidine 
• 6627-53-8 1-chloro-3-methoxy-4-nitrobenzene 
• 1027042-31-4 8-(tert-butyl-dimethyl-silanyloxy)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one 

Relevant articles and documents

Characterization of marmoset CYP2B6: CDNA cloning, protein expression and enzymatic functions

The common marmoset is a promising species for evaluating the safety of drug candidates. To further understand the capacity for drug metabolism in marmosets, a cDNA encoding a CYP2B enzyme was cloned from the total RNA fraction of marmoset liver by 3′- and 5′-RACE methods. Nucleotide and deduced amino acid sequences showed 90.8 and 86.2% identity, respectively, with human CYP2B6. The marmoset CYP2B6 (marCYP2B6) protein was expressed in insect cells, and its enzymatic properties were compared with those of human (humCYP2B6) and cynomolgus monkey (cynCYP2B6) orthologs in liver and insect cell microsomes. Enzymatic functions were examined for the oxidation of 7-ethoxy-4-(trifluoromethyl)coumarin (7-ETC), bupropion (BUP) and efavirenz (EFV). The kinetic profiles for the oxidation of the three substrates by liver microsomal fractions were similar between humans and cynomolgus monkeys (biphasic for 7-ETC and monophasic for BUP and EFV), but that of marmosets was unique (monophasic for 7-ETC and biphasic for BUP and EFV). Recombinant enzymes, humCYP2B6 and cynCYP2B6, also yielded similar kinetic profiles for the oxidation of the three substrates, whereas marCYP2B6 showed activity only for 7-ETC hydroxylation. In silico docking simulations suggested that two amino acid residues, Val-114 and Leu-367, affect the activity of marCYP2B6. In fact, a marCYP2B6 mutant with substitutions V114I and L367V exhibited BUP hydroxylase activity that was 4-fold higher than that of humCYP2B6, while its EFV 8-hydroxylase activity was only 10% that of the human enzyme. These results indicate that the amino acids at positions 114 and 367 affect the enzymatic capacity of marmoset CYP2B6.

The phenolic metabolites of the anti-HIV drug efavirenz: Evidence for distinct reactivities upon oxidation with Fre?my's salt

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor administered as first line treatment against HIV-1. The major drawbacks of EFV therapy are neurotoxicity and hepatotoxicity, which may result from bioactivation to reactive metabolites capable of reacting with bionucleophiles. We investigated the in vitro oxidation of the phenolic EFV metabolites, 7-hydroxy-efavirenz (7-OH-EFV) and 8-hydroxy-efavirenz (8-OH-EFV), with Frémy's salt. A quinoline derivative, 6-chloro-2-cyclopropyl-4- (trifluoromethyl)quinolin-7-ol, presumably stemming from a radical rearrangement, was selectively obtained from 7-OH-EFV in 10% yield. In contrast, when subjected to the same oxidation conditions, 8-OH-EFV was considerably more prone to oxidative degradation and yielded multiple products. Among these, a quinone-imine derivative was tentatively identified upon LC-ESI-MS/MS analysis of the reaction mixture. These observations demonstrate a remarkable difference in the reactivities of the two phenolic EFV metabolites under oxidative conditions. Moreover, taking into consideration the toxicological significance of quinone-imine derivatives, these findings may explain earlier reports that 8-OH-EFV is a more potent toxicant than 7-OH-EFV in model test systems.

4,4-DISUBSTITUTED-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONES USEFUL AS HIV REVERSE TRANSCRIPTASE INHIBITORS AND INTERMEDIATES AND PROCESSES FOR MAKING THE SAME

The present invention relates to benzoxazinones of formula I, or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.