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

Molecular Formula	C17H22N2O3
Molecular Weight	302.3682
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Effect of human serum on the in vitro anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives as related to their lipophilicity and serum protein binding.	1993 Jun 22	8328988
Selective and synergistic inhibition of human immunodeficiency virus type 1 reverse transcriptase by a non-nucleoside inhibitor, MKC-442.	1993 Oct	7694070
Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.	1995 Jul 21	7636846
The inhibition of human immunodeficiency virus type 1 in vitro by a non-nucleoside reverse transcriptase inhibitor MKC-442, alone and in combination with other anti-HIV compounds.	1995 Mar	7541619
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
Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication.	1996 Aug	8700148
Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine.	1996 Jun 7	8691437
Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase.	1998 Dec	9835518
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
A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152.	1998 Jun	9634074
5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series.	1998 Jun 16	9873370
Activity of non-nucleoside reverse transcriptase inhibitors against HIV-2 and SIV.	1999 Aug 20	10465070
N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1.	1999 Dec 20	10617082
Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.	1999 Nov 4	10579814
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
Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors.	2000 May	10779379
Estimation of binding affinities for HEPT and nevirapine analogues with HIV-1 reverse transcriptase via Monte Carlo simulations.	2001 Jan 18	11170624
Three-drug combinations of emivirine and nucleoside reverse transcriptase inhibitors in vitro: long-term culture of HIV-1-infected cells and breakthrough viruses.	2001 May	12959324
New developments in anti-HIV chemotherapy.	2001 Nov	11562282
Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails.	2002 Jan 1	11782585
Prediction of activity for nonnucleoside inhibitors with HIV-1 reverse transcriptase based on Monte Carlo simulations.	2002 Jul 4	12086483
Synthesis of furoannelated analogues of Emivirine (MKC-442).	2004 Mar	15038059
Gateways to clinical trials.	2004 May	15319808
4-benzyl- and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones, a new family of potent anti-HIV agents: optimization and in vitro evaluation against clinically important HIV mutant strains.	2004 Oct 21	15481987
5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO family.	2005 Mar 15	15727860
Chemo- and regioselective functionalization of uracil derivatives. Applications to the synthesis of oxypurinol and emivirine.	2006 Aug 17	16898805
Synthesis and anti-HIV-1 activity of new MKC-442 analogues with an alkynyl-substituted 6-benzyl group.	2007 May	17464964

Patents

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:39:14 UTC 2023` Edited by `admin` on `Fri Dec 15 15:39:14 UTC 2023`
Record UNII	X87G8IX72O
Record Status	`Validated (UNII)`
Record Version

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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