Delving into the Latest Updates on Emivirine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-(ethoxymethyl)-5-(1-methylethyl)-6-(phenylmethyl)pyrimidine-2,4(1H,3H)-dione, 6-benzyl-1-(ethoxymethyl)-5-(1-methylethyl)uracil, Emivirine (USAN/INN)

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Target

RT

Action

inhibitors

Mechanism

RT inhibitors(Viral reverse transcriptase inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication

Brain Cancer

Originator Organization

Tanabe Pharma Corp.

Active Organization

University of Southern Denmark

Inactive Organization

Triangle Pharmaceuticals, Inc.

Abbott Laboratories

Tanabe Pharma Corp.

+ [1]

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC17H22N2O3

InChIKeyMLILORUFDVLTSP-UHFFFAOYSA-N

CAS Registry149950-60-7

A Phase II, 24-Week, Open-Label Study Designed to Evaluate the Pharmacokinetics, Safety, Tolerability, and Efficacy of Novel Combination Therapy With Videx (Didanosine), Zerit (Stavudine), Rescriptor (Delavirdine Mesylate), and MKC-442 (With or Without Hydroxyurea) for the Treatment of HIV-1- Infected Patients Who Failed Previous Protease Inhibitor Treatment

The purpose of this study is to see if it is safe and effective to give MKC-442, didanosine (ddI), stavudine (d4T), and delavirdine (DLV) to HIV-positive patients.

Start Date-

Sponsor / Collaborator

Bristol Myers Squibb Co.

[+2]

NCT00002413

/ CompletedPhase 2

An Open Label Study of MKC-442 in at Least Triple Drug Combination in Patients Previously Treated With Nucleoside Reverse Transcriptase and Protease Inhibitors and Who Are Naive to Non-Nucleoside Reverse Transcriptase Inhibitors

The purpose of this study is to see if it is safe and effective to give MKC-442 plus at least two other anti-HIV drugs to patients who have never been treated with nonnucleoside reverse transcriptase inhibitors but who have been treated with nucleoside reverse transcriptase inhibitors and protease inhibitors. This study also determines how long a drug combination including MKC-442 is effective.

Start Date-

Sponsor / Collaborator

Triangle Pharmaceuticals, Inc.

NCT00002418

/ TerminatedPhase 2

A Phase II, 24-Week, Open-Label Study Designed to Evaluate the Pharmacokinetics, Safety, Tolerability, and Efficacy of Novel Combination Therapy With Videx (Didanosine), Zerit (Stavudine), Viramune (Nevirapine), and MKC-442 (With or Without Hydroxyurea) for the Treatment of HIV-1 Infection in Non-Nucleoside Reverse Transcriptase Inhibitor Naive Patients Who Failed Previous Protease Inhibitor Treatment

The purpose of this study is to see if it is safe and effective to give a new anti-HIV drug combination to HIV-infected patients who have never taken nonnucleoside reverse transcriptase inhibitors (NNRTIs) and who have failed to respond to protease inhibitors (PIs). The drug combination will contain didanosine (ddI) plus stavudine (d4T) plus nevirapine (NVP) plus MKC-442. Hydroxyurea (HU) may be added.

Start Date-

Sponsor / Collaborator

Bristol Myers Squibb Co.

[+2]

100 Clinical Results associated with Emivirine

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100 Translational Medicine associated with Emivirine

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100 Patents (Medical) associated with Emivirine

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126

Literatures (Medical) associated with Emivirine

01 Oct 2017·MONATSHEFTE FUR CHEMIE

A prediction approach for anti-HIV activity of HEPT compounds using random forest technique

Author: Lawtrakul, Luckhana ; Nattee, Cholwich ; Inthajak, Krit ; Toochinda, Pisanu ; Khamsemanan, Nirattaya

The human immunodeficiency virus type 1 (HIV-1) is one of the deadliest viruses that affect public health worldwide.Joint United Nations Program on HIV/AIDS (UNAIDS) and World Health Organization estimate that there are more than 15 million people infected with this HIV-1 around the world.The cure of HIV-1 and a better understanding of effective drugs are urgently needed.In this work, we study the structure-activity relationship and predict the potency of HIV-1 drug compoundsWe employ the random forest technique to select relevant mol. descriptors of 132 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) compounds toward the inhibition of HIV-1 reverse transcriptase (RT).The best model yields 5 relevant descriptors with a coefficient of determination (R²) of 0.83.Our prediction model suggests that a potent HEPT compound must be a lipophilic mol. with a high value of fractional hydrophobic van der Waals surface areas.

01 Feb 2015·Antiviral chemistry & chemotherapy

Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives

Article

Author: Demizu, Yosuke ; Okamoto, Mika ; Toyama, Masaaki ; Kato, Yoshihisa ; Maruyama, Tokumi ; Baba, Masanori ; Kurihara, Masaaki ; Irie, Kohji ; Sakakibara, Norikazu ; Misawa, Takashi

Background:

A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors.

Methods:

A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells.

Results:

Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure–activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents.

Conclusion:

The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 ± 0.006 µM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants.

26 Jun 2014·Journal of medicinal chemistryQ1 · MEDICINE

Synthesis of Novel Fluoro Analogues of MKC442 as Microbicides

Q1 · MEDICINE

Article

Author: Giliberti, Gabriele ; Sanna, Giuseppina ; Loksha, Yasser M. ; Collu, Gabriella ; Colla, Paolo La ; Loddo, Roberta ; Pedersen, Erik B.

Novel analogues of MKC442 (6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione) were synthesized by reaction of 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyluracil (5) with ethoxymethyl chloride and formaldehyde acetals. The Sonogashira reaction was carried out on the N1-(p-iodobenzyl)oxy]methyl derivative of compound 5 using propagyl alcohol to afford compound 12 (YML220). The latter compound was selected for further studies since it showed the most potent and selective activity in vitro against wild-type HIV-1 and non-nucleoside reverse transcriptase inhibitor-, nucleoside reverse transcriptase inhibitor-, and protease inhibitor-resistant mutants and a wide range of HIV-1 clinical isolates. 12 also showed microbicidal activity in long-term assays with heavily infected MT-4 cells.

100 Deals associated with Emivirine

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External Link

KEGG	Wiki	ATC	Drug Bank
D01055	Emivirine	-	DB08188

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 3	European Union	-	-
HIV Infections	Phase 3	Mexico	-	-
HIV Infections	Phase 3	South Africa	-	-
HIV Infections	Phase 3	-	Gilead Sciences, Inc.	-
HIV Infections	Phase 3	-	Tanabe Pharma Corp.	-
HIV Infections	Phase 3	-	Abbott Laboratories	-
Brain Cancer	Phase 2	United States	-	-
Brain Cancer	Phase 2	-	Gilead Sciences, Inc.	-
Brain Cancer	Phase 2	-	Abbott Laboratories	-
Brain Cancer	Phase 2	-	Tanabe Pharma Corp.	-