A Phase I, Multicenter, Randomized, Parallel, Double-Blinded Dose Ranging, Placebo-Controlled Study to Compare Antiviral Effect, Safety, Tolerability and Pharmacokinetics of Four Oral Dosage Regimens of GW695634G Monotherapy Versus Placebo Over 10 Days in ART-Naive HIV-1 Infected Adults.

To investigate safety, tolerability and antiviral activity in Non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced HIV-1 infected patients

Start Date01 Apr 2004

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GW-695634

100 Translational Medicine associated with GW-695634

100 Patents (Medical) associated with GW-695634

Literatures (Medical) associated with GW-695634

05 May 2017·Medicinal ChemistryQ4 · MEDICINE

Synthesis and Biological Evaluation of Benzophenone Derivatives as Potential HIV-1 Inhibitors

Q4 · MEDICINE

Article

Author: Wang, Rui-Rui ; Liu, Kexin ; Wang, Changyuan ; Huang, Shanshan ; Ma, Xiaodong ; Yang, Liu-Meng ; Wang, Ping ; Zheng, Yong-Tang ; Song, Zhendong ; Zhen, Yuhong

BACKGROUNDAlthough a number of agents can achieve high response in acquired immunodeficiency syndrome (AIDS) patients, safer and more active HIV inhibitors are still needed for the growing number of patients infected with resistant HIV virus strains. GW678248, is one of the most potent benzophenone derivatives, exhibiting high potency against a panel of HIV-1 virus (wild-type, K103N mutant, Y181C, etc.) at 1 nM/L concentrations. However, the safety issues associated with rash and liver metabolic enzymes ultimately led to discontinue its further development. As a continuation of our structural modifications on this template, in this manuscript, a new series of benzophenones are described as potential HIV inhibitors.METHODSAll the title molecules were synthesized according to the routes in scheme 1 and scheme 2, and were tested for anti-HIV-1 activity using the MTT method. In the molecular simulation, the docking program of AutoDock 4.0.1 in parallel with the default parameters were used.RESULTSA series of novel benzophenone derivatives (BPs) with nanomolar anti-HIV-1 activity was identified. Of these inhibitors, analogue 10i (EC50 = 2.9 nmol/L), the most active inhibitor, was comparable to the lead compound in inhibiting the wild-type HIV-1 virus. Additionally, analogue 13b, which not only exhibited strong inhibitory activity against the HIV-1 virus (EC50 = 4.2 nmol/L), but also has very low cytotoxicity with a TI value of more than 219178.1 was also discovered.CONCLUSIONThis study led to the identification of a series of benzophenone derivatives with nanomolar level of anti-HIV-1 activity. Analogue 10i and analogue 13b, with low cytotoxicity along with high activity are worthy of further development.

01 Feb 2016·Chemical Biology & Drug DesignQ4 · MEDICINE

Design, Synthesis, and Biological Evaluation of Novel 2‐(Pyridin‐3‐yloxy)acetamide Derivatives as Potential Anti‐HIV‐1 Agents

Q4 · MEDICINE

Article

Author: Huang, Boshi ; De Clercq, Erik ; Pannecouque, Christophe ; Daelemans, Dirk ; Li, Xiao ; Liu, Xinyong ; Zhan, Peng

Through a structure‐based molecular hybridization and bioisosterism approach, a series of novel 2‐(pyridin‐3‐yloxy)acetamide derivatives were designed, synthesized, and evaluated for their anti‐HIV activities in MT‐4 cell cultures. Biological results showed that three compounds (Ia, Ih, and Ij) exhibited moderate inhibitory activities against wild‐type (wt) HIV‐1 strain (IIIB) with EC50 values ranging from 8.18 μm to 41.52 μm. Among them, Ij was the most active analogue possessing an EC50 value of 8.18 μm. To further confirm the binding target, four compounds were selected to implement an HIV‐1 RT inhibitory assay. In addition, preliminary structure–activity relationship (SAR) analysis and some predicted physicochemical properties of three active compounds Ia, Ih, and Ij were discussed in detail. Molecular docking studies were also carried out to investigate the binding modes of Ij and the lead compound GW678248 in the binding pocket of RT, which provided beneficial information for further rational design of non‐nucleoside reverse transcriptase inhibitors.

01 Dec 2012·European Journal of Medicinal ChemistryQ1 · MEDICINE

Synthesis, structure–activity relationships, and docking studies of N-phenylarylformamide derivatives (PAFAs) as non-nucleoside HIV reverse transcriptase inhibitors

Q1 · MEDICINE

Article

Author: Fen-Er Chen ; Liu-Meng Yang ; Shi-Qiong Yang ; Xiao-Dong Ma ; Hui-Fang Dai ; Xuan Zhang ; Yong-Tang Zheng ; Shuang-Xi Gu ; Qiu-Qin He

A series of N-phenylarylformamide derivatives (PAFAs) with anti-wild-type HIV-1 activity (EC(50) values) ranging from 0.3 nM to 5.1 nM and therapeutic index (TI) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. Among them, compound 13g (EC(50) = 0.30 nM, TI = 184 578), 13l (EC(50) = 0.37 nM, TI = 212 819), 13m (EC(50) = 0.32 nM, TI = 260 617) and 13r (EC(50) = 0.27 nM, TI = 271 000) displayed the highest activity against this type virus nearly as potent as lead compound GW678248. Moreover, all of them were also active to inhibit the double mutant strain A(17) (K103N + Y181C) with EC(50) values of 0.29 μM, 0.14 μM, 0.10 μM and 0.27 μM, respectively. In particular, compound 13m, which showed broad-spectrum anti-HIV activity, was also effective to inhibit the HIV-2 ROD replication within 4.37 μM concentration.

100 Deals associated with GW-695634

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	US	GSK Plc	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NN210005 (IAS2005)	Not Applicable	HIV Infections	46	GW695634 100mg	(acysbdxiej) = 11% gxifvltelj (xermvllwel ) View more	Positive	01 Jan 2005
				GW695634 200mg

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