Delving into the Latest Updates on Brecanavir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Brecanavir (USAN), GW 0385, GW 640385

+ [6]

Target

HIV-1 protease

Mechanism

HIV-1 protease inhibitors(HIV protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

HIV Infections

Originator Organization

Vertex Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

ViiV Healthcare Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC33H41N3O10S2

InChIKeyJORVRJNILJXMMG-OLNQLETPSA-N

CAS Registry313682-08-5

Phase IIB, Randomized, Multicenter, Parallel Group, Study to Evaluate the Safety, Pharmacokinetics and Antiviral Effect of Four Blinded Dosing Regimens of GW640385X/Ritonavir Compared to Open-label Current PI Therapy in HIV-1 Infected, Protease Inhibitor Experienced Adults for 2 Weeks With Long-term Assessment (>48 Weeks) of Safety, Pharmacokinetic and Antiviral Activity of Selected 385/RTV Dosing Regimen(s) vs. a Ritonavir-boosted, Protease Inhibitor Containing Regimen

This is a two phase study (randomised and non-randomised phase). The randomised phase will initially examine 4 blinded doses of GW640385 boosted with rtv (with continuation of current background therapy) in comparison to an ongoing, open-labeled rtv-boosted protease inhibitor (PI) regimen for 15 days. At the Day 15 visit, all subjects will optimize background therapy. Additionally, subjects receiving the lowest dose of GW640385 will be re-randomised to one of the higher doses and subjects in the control arm will receive a new rtv-boosted PI based on resistance testing at screening. Subjects will remain in the randomized phase on one of these 4 continuing treatment arms for at least 48 weeks. An interim analysis will occur during the randomised phase to select for a dose of GW640385 to evaluate further in Phase III studies. After dose selection subjects will move to the non-randomised phase of the study. In the non-randomised phase subjects who are receiving GW640385 will be assigned to final selected dose for assessment of long term safety, tolerability, pharmacokinetics, and antiviral activity.

Start Date01 Aug 2005

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT00257621 / CompletedPhase 2

A Pilot, Phase II, Open-label, Single Arm Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of GW640385 When Administered With Ritonavir in Combination With NRTIs for 48 Weeks in HIV-1 Infected Adults

This is a proof of concept (POC) single arm study of GW640385, a protease inhibitor, in combination with RTV and 2 or more nucleoside reverse transcriptase inhibitors (NRTI) backbone. This study has a 48 week duration and is open to both treatment naive and experienced patients who are HIV positive. There are 3 intensive pharmacokinetic (PK) visits.

Start Date01 Oct 2004

Sponsor / Collaborator

ViiV Healthcare Ltd.

100 Clinical Results associated with Brecanavir

Login to view more data

100 Translational Medicine associated with Brecanavir

Login to view more data

100 Patents (Medical) associated with Brecanavir

Login to view more data

12

Literatures (Medical) associated with Brecanavir

01 Dec 2018·Chemistry Central journal

Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents

Article

Author: Mabkhot, Yahia N ; Al-Showiman, Salim S ; Ghabbour, Hazem A ; Kheder, Nabila A ; Alharbi, Mohammed M ; Soliman, Saied M ; Frey, Wolfgang

BACKGROUND:

The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen.

RESULTS:

Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity.

CONCLUSIONS:

Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

01 May 2013·European journal of medicinal chemistryQ1 · MEDICINE

Synthesis and pharmacokinetic profile of highly deuterated brecanavir analogs

Q1 · MEDICINE

Article

Author: Weatherhead, Jason G. ; Johns, Brian A. ; Temelkoff, David P. ; Velthuisen, Emile J. ; Baughman, Todd M.

Several highly deuterated analogs of the HIV-1 protease inhibitor brecanavir have been prepared to study the effect of deuterium upon metabolic stability. The sites for deuterium incorporation were initially chosen to maximize the potential for a kinetic isotope effect; locations where C-H bond breaking is the rate limiting step. The analogs have been profiled in both in vitro and in vivo pharmacokinetic studies and the result will be described herein.

01 Nov 2008·Current opinion in HIV and AIDSQ3 · MEDICINE

Approaches to the design of HIV protease inhibitors with improved resistance profiles

Q3 · MEDICINE

Article

Author: Gulnik, Sergei V ; Eissenstat, Michael

PURPOSE OF REVIEW:

This review describes current approaches to HIV protease inhibitor design, with a focus on improving their profile against drug-resistant mutants. Potential explanations for the flat resistance profile of some potent protease inhibitors and discrepancies between the apparent fold change of potency at the enzyme level and in cell-based assays are discussed.

RECENT FINDINGS:

Despite new ideas and a clear rationale for designing inhibitors that bind outside the enzyme active site, all current protease inhibitors with potent antiviral activity target this site. Several bis-tetrahydrofuran-containing compounds including darunavir, brecanavir, GS-8374, and Sequoia protease inhibitors exhibit excellent potency against mutant HIV strains that are resistant to clinically used protease inhibitors. The apparently flat resistance profiles of these and some other protease inhibitors may, at least in part, be explained by their high potency against wild-type enzyme. The substrate envelope and solvent-anchoring hypotheses have been used to design and/or rationalize improved resistance profiles. Traditional approaches yielded a lysine sulfonamide PL-100 with a unique resistance profile.

SUMMARY:

Several theories on how to design HIV protease inhibitors with improved resistance profiles have been proposed during the review period. The general concepts that are incorporated into most design strategies include maximizing the interactions with the backbone and conserved side chains of the enzyme while minimizing inhibitor size and maintaining conformational flexibility to allow for modified binding modes.

100 Deals associated with Brecanavir

Login to view more data