BRECANAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H41N3O10S2
Molecular Weight	703.823
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12OCC[C@@]1([H])[C@H](CO2)OC(=O)N[C@@H](CC3=CC=C(OCC4=CSC(C)=N4)C=C3)[C@H](O)CN(CC(C)C)S(=O)(=O)C5=CC=C6OCOC6=C5

InChI

InChIKey=JORVRJNILJXMMG-OLNQLETPSA-N

InChI=1S/C33H41N3O10S2/c1-20(2)14-36(48(39,40)25-8-9-29-30(13-25)45-19-44-29)15-28(37)27(35-33(38)46-31-17-43-32-26(31)10-11-41-32)12-22-4-6-24(7-5-22)42-16-23-18-47-21(3)34-23/h4-9,13,18,20,26-28,31-32,37H,10-12,14-17,19H2,1-3H3,(H,35,38)/t26-,27-,28+,31-,32+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16723584 | https://web.archive.org/web/20081203151032/http://www.gsk.com/media/pressreleases/2006/2006_12_18_GSK945.htm

Brecanavir (previously known as VX-385), a HIV aspartyl protease inhibitor was developed for the treatment of HIV. The inhibition of HIV viral proteinase enzyme prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles. Brecanavir reached Phase II development. However, GlaxoSmithKline announced to discontinue development brecanavir. Because of the inability to develop a viable oral dosage formulation capable of delivering the desired brecanavir levels in patients with multi-drug resistant HIV.

Originator

Approval Year

PubMed

Title	Date	PubMed
Inhibition of wild-type and mutant human immunodeficiency virus type 1 proteases by GW0385 and other arylsulfonamides.	2004 Nov 16	15533054
Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.	2006 Apr 1	16458505
Single-dose safety and pharmacokinetics of brecanavir, a novel human immunodeficiency virus protease inhibitor.	2006 Jun	16723584
In vitro development of resistance to human immunodeficiency virus protease inhibitor GW640385.	2006 Mar	16495277
Safety and pharmacokinetics of brecanavir, a novel human immunodeficiency virus type 1 protease inhibitor, following repeat administration with and without ritonavir in healthy adult subjects.	2007 Apr	17261626
Preliminary safety and efficacy data of brecanavir, a novel HIV-1 protease inhibitor: 24 week data from study HPR10006.	2007 Jul	17491001
In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV.	2007 Sep	17620375
Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization.	2007 Sep 28	17635930
Recent developments of peptidomimetic HIV-1 protease inhibitors.	2011	21864279
GS-8374, a prototype phosphonate-containing inhibitor of HIV-1 protease, effectively inhibits protease mutants with amino acid insertions.	2014 Mar	24371077

Sample Use Guides

In Vivo Use Guide

In part 1 of the study, single oral doses of Brecanavir (BCV) ranged from 25 mg to 800 mg. In part 2, single oral doses of BCV ranged from 10 mg to 300 mg and were coadministered with 100-mg oral ritonavir (RTV) soft gel capsules. Single doses of BCV and BCV/RTV were generally well tolerated. There were no severe adverse events (SAEs), and no subject was withdrawn due to BCV.

Route of Administration: Oral

Name

Type

Language

BRECANAVIR

Official Name

English

GW64085X

Code

English

BRECANAVIR [USAN]

Common Name

English

GW-640385

Code

English

GW-640385X

Code

English

GW640385

Code

English

Brecanavir [WHO-DD]

Common Name

English

brecanavir [INN]

Common Name

English

(3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL((1S,2R)-3-((1,3,BENZODIOXOL-5-YLSULFONYL)2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(4-((2-METHYLTHIOZOL-5-YL)METHOXY)BENZYL)PROPYL)CARBAMATE

Common Name

English

CARBAMIC ACID, ((1S,2R)-3-((1,3-BENZODIOXOL-5-YLSULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-((4-((2-METHYL-4-THIAZOLYL)METHOXY)PHENYL)METHYL)PROPYL)-, (3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ESTER

Common Name

English

GW-64085X

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C97366