Diphenyl ethers (DPE) and its analogs have exhibited excellent potential for therapeutic and industrial applications. Since the 19th century, intensive research is perpetuating on the synthetic routes and biological properties of DPEs. Few well-known DPEs are Nimesulide, Fenclofenac, Triclosan, Sorafenib, MK-4965, and MK-1439 which have shown the potential of this moiety as a lead scaffold for different pharmacological properties. In this review, we recapitulate the diverse synthetic route of DPE moiety inclusive of merits and demerits over the classical synthetic route and how this moiety sparked an interest in researchers to discern the SAR (Structure Activity Relationship) for the development of diversified biological properties of DPEs such as antimicrobial, antifungal, antiinflammatory & antiviral activities.

01 Mar 2013·Current Pharmaceutical DesignQ4 · MEDICINE

Recent Advances of Diaryl Ether Family as HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

Q4 · MEDICINE

Review

Author: Chen, Xuwang ; Liu, Xinyong ; Ding, Shufang ; Zhan, Peng

Diaryl ether family as one of the promising second generation HIV-1 non-nucleoside reverse transcriptase inhibitors has attracted considerable attention over the past few years, among which clinical candidate MK-4965 has been advanced into phase II clinical trials. The successful development of diaryl ether family provides valuable avenues in traditional medicinal chemistry, crystallography and computer-aided drug design fields for the design of other novel anti-HIV drug candidates. In this review, the development of diaryl ether family is present including the evolutionary history, design strategies, extensive structural modifications, structure-activity relationship studies and computer-aided molecular simulation of the binding mode in detail.

26 Apr 2012·Journal of Medicinal ChemistryQ1 · MEDICINE

Strategies for the Design of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Lessons from the Development of Seven Representative Paradigms

Q1 · MEDICINE

Article

Author: De Clercq, Erik ; Li, Dongyue ; Zhan, Peng ; Liu, Xinyong

A review.Non-nucleoside reverse transcriptase inhibitors (NNRTIs) in clin. use, such as nevirapine, delavirdine, efavirenz, etravirine and rilpivirine, a new drug approved by FDA recently, are key components of standard highly active antiretroviral therapy (HAART) against HIV infection.Despite great improvements in NNRTI efficacy and resistance profiles, there is still an urgent need for novel drugs possessing high potency with overcoming drug resistance, less toxicity with good patient adherence, and better pharmacokinetic properties.Currently, the 3-dimensional structure of HIV reverse transcriptase (RT) has been elucidated, but the inherent flexibility and mutability of the NNRTI binding pocket (NNIBP) still limit the structure-based NNRTI design.With the continued efforts in the development of computational tools and increased structural information on reverse transcriptase, coordinated multidisciplinary efforts involving medicinal chem. (bioisosterism, mol. hybridization, scaffold hopping and fragment-based drug discovery), structural biol. (crystallog.), and computational chem. (mol. modeling), have proven to be powerful strategies to handle the flexibility and mutability of the NNIBP for identifying new generation of NNRTIs.In this review, we took a look at the convoluted development routes of seven representative drugs and candidates (i.e., etravirine, rilpivirine, IDX-899, RDEA806, UK-453061, MK-4965 and BILR 355) that entered into clin. trials in the past 5 years, to highlight various drug design strategies implemented with a multidisciplinary approach so as to offer useful references to medicinal chemists for the discovery and development of novel NNRTIs.Furthermore, an elaborate pharmacophore model with same pharmacophoric features, and ubiquitous motifs of the halogenphenyl and nitrile groups that served as "privileged scaffolds" in fragment-based NNRTIs discovery strategy, are also specifically addressed.

100 Deals associated with MK-4965

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 1	US	Merck GmbH	-
HIV Infections	Phase 1	-	Merck Sharp & Dohme Corp.	-

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