EMIVIRINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H22N2O3
Molecular Weight	302.3682
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOCN1C(=O)NC(=O)C(C(C)C)=C1CC2=CC=CC=C2

InChI

InChIKey=MLILORUFDVLTSP-UHFFFAOYSA-N

InChI=1S/C17H22N2O3/c1-4-22-11-19-14(10-13-8-6-5-7-9-13)15(12(2)3)16(20)18-17(19)21/h5-9,12H,4,10-11H2,1-3H3,(H,18,20,21)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7694070 | https://www.ncbi.nlm.nih.gov/pubmed/11367264 | https://adisinsight.springer.com/drugs/800002827

MKC-442 (6-benzyl-1-(ethoxymethyl)-5-isopropyl-uracil) is a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Emivirine structurally is a nucleoside analog (NRTI) molecule, but it functions as a non-nucleoside reverse transcriptase inhibitor (NNRTI). Emivirine had reached phase 3 clinical trials for the treatment of HIV-1 infections before its further development was stopped.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7694070	Inhibitor 8297		8.0 nM [IC50]

PubMed

Title	Date	PubMed
Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of human immunodeficiency virus type 1 in vitro.	1994 Apr	7518216
Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives).	1995 Jun 6	7539917
Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors.	1996 Apr 12	8648598
Marked inhibitory activity of non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus type 1 when combined with (-)2',3'-dideoxy-3'-thiacytidine.	1996 May	8622638
Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase.	1998 Dec	9835518
Synthesis and anti-HIV-1 activity of novel 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones.	1998 Jan 15	9457243
Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an omega-functionalized acyclic structure.	1998 Jul	9875411
Preclinical studies on thiocarboxanilide UC-781 as a virucidal agent.	1998 Jul 9	9677161
Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus.	1999 Jun 7	10386942
Inhibition of human immunodeficiency virus type 1 replication in acutely and chronically infected cells by EM2487, a novel substance produced by a Streptomyces species.	1999 Oct	10508005
Structure-based design of non-nucleoside reverse transcriptase inhibitors of drug-resistant human immunodeficiency virus.	1999 Sep	10574178
N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea and N'-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-chloropyridyl)]-thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1.	1999 Sep 20	10509923
Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors.	2000 Apr 10	10777142
Structure-activity relationship studies on potential non-nucleoside DABO-like inhibitors of HIV-1 reverse transcriptase.	2000 Mar	10819436
Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138.	2001 Feb 1	11162823
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
Synthesis of novel N-1 (allyloxymethyl) analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine) with improved activity against HIV-1 and its mutants.	2002 Dec 19	12477355
New anti-HIV agents and targets.	2002 Nov	12369088
Multiple pathways in the synthesis of new annelated analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (emivirine).	2003 Aug 21	12968341
Gateways to clinical trials.	2003 Jan-Feb	12690708
Gateways to clinical trials.	2003 Oct	14671684
Gateways to clinical trials.	2004 May	15319808
The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase.	2006 Sep 7	17036113
Functionalization of unprotected uracil derivatives using the halogen-magnesium exchange.	2007 Apr 26	17388601
Synthesis of novel uracil non-nucleoside derivatives as potential reverse transcriptase inhibitors of HIV-1.	2009 Nov	19856332

Patents

Name

Type

Language

EMIVIRINE

Official Name

English

COACTINON

Brand Name

English

Emivirine [WHO-DD]

Common Name

English

EMIVIRINE [MART.]

Common Name

English

2,4(1H,3H)-PYRIMIDINEDIONE, 1-(ETHOXYMETHYL)-5-(1-METHYLETHYL)-6-(PHENYLMETHYL)-

Systematic Name

English

MKC-442

Code

English

emivirine [INN]

Common Name

English

EMIVIRINE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C97453