NARLAPREVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C36H61N5O7S
Molecular Weight	707.964
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CN([C@H](C(=O)N[C@@H](CCCC)C(=O)C(=O)NC3CC3)[C@@]1([H])C2(C)C)C(=O)[C@@H](NC(=O)NC4(CS(=O)(=O)C(C)(C)C)CCCCC4)C(C)(C)C

InChI

InChIKey=RICZEKWVNZFTNZ-LFGITCQGSA-N

InChI=1S/C36H61N5O7S/c1-10-11-15-24(27(42)30(44)37-22-16-17-22)38-29(43)26-25-23(35(25,8)9)20-41(26)31(45)28(33(2,3)4)39-32(46)40-36(18-13-12-14-19-36)21-49(47,48)34(5,6)7/h22-26,28H,10-21H2,1-9H3,(H,37,44)(H,38,43)(H2,39,40,46)/t23-,24-,25-,26-,28+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C36H61N5O7S
Molecular Weight	707.964
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.r-pharm.com/en/press-center/news/290 | https://adisinsight.springer.com/drugs/800029288 | https://www.ncbi.nlm.nih.gov/pubmed/27645244

Narlaprevir (formerly SCH 900518), a NS3 protease inhibitor is being developed by R-Pharm for the treatment of a chronic hepatitis C (genotype 1). Narlaprevir is a potent inhibitor of hepatitis C virus (HCV) NS3 protease with a Ki of 7 ± 1 nM and a 90% inhibitory concentration (IC90) of ∼28 ng/ml for HCV genotype 1 replicon in vitro. Narlaprevir successfully passed extensive pre-clinical and clinical trials in Schering-Plough Research Institute (USA) and in a variety of clinical centers of Europe, USA and Russia. Based on clinical findings R-Pharm obtained a registration certificate for Arlansa (Narlaprevir) ЛП-003622 dd 12.05.2016 issued by Ministry of Healthcare of the Russian Federation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatitis C virus NS3 protease/helicase 5 Target ID: CHEMBL4893 Sources: https://pubs.acs.org/doi/abs/10.1021/ml9000276	Inhibitor 8297		6.0 nM [Ki]

PubMed

Title	Date	PubMed
Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease.	2010 Jun	20308381
Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients.	2010 Nov	20938912
Insight into the structural requirements of narlaprevir-type inhibitors of NS3/NS4A protease based on HQSAR and molecular field analyses.	2012 Jul	22263860
Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor.	2013 Nov	24168257

Sample Use Guides

In Vivo Use Guide

Narlaprevir at 200 mg was administered to 8 healthy and 8 cirrhotic subjects, and Narlaprevir at 100 mg with RTV at 100 mg was administered to 8 healthy and 8 cirrhotic subjects. In part 1 of the study, 8 patients with compensated cirrhosis and 8 matched healthy adult subjects received single doses of NVR at 200 mg with 240 ml of water after a standard breakfast. The 200-mg NVR dose was chosen since this is the intended therapeutic dose. This dose is the approved marketed dose of NVR for the treatment of CHC genotype 1 in the Russian Federation. In part 2 of the study, 8 patients with compensated cirrhosis and 8 healthy subjects received NVR at 100 mg in combination with RTV at 100 mg with 240 ml of water after a standard breakfast.

Route of Administration: Oral

In Vitro Use Guide

Narlaprevir is a potent inhibitor of hepatitis C virus (HCV) NS3 protease with a Ki of 7 ± 1 nM and a 90% inhibitory concentration (IC90) of ∼28 ng/ml for HCV genotype 1 replicon in vitro.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:53:25 UTC 2023` Edited by `admin` on `Fri Dec 15 16:53:25 UTC 2023`
Record UNII	2857LA2O07
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NARLAPREVIR

Official Name

English

(1R,2S,5S)-3-(N-(((1-((TERT-BUTYLSULFONYL)METHYL)CYCLOHEXYL)AMINO)CARBONYL)-3-METHYL-L- VALYL)-N-((1S)-1-((CYCLOPROPYLAMINO)(OXO)ACETYL)PENTYL)-6,6-DIMETHYL-3- AZABICYCLO(3.1.0)HEXANE-2-CARBOXAMIDE

Common Name

English

(1R,2S,5S)-N-((1S)-1-(2-(CYCLOPROPYLAMINO)-2-OXOACETYL)PENTYL)-3-((2S)-2-(((1-(((1,1- DIMETHYLETHYL)SULFONYL)METHYL)CYCLOHEXYL)CARBAMOYL)AMINO)-3,3-DIMETHYLBUTANOYL)-6,6- DIMETHYL-3-AZABICYCLO(3.1.0)HEXANE-2-CARBOXAMIDE

Common Name

English

SCH-900518

Code

English

NARLAPREVIR [USAN]

Common Name

English

3-AZABICYCLO(3.1.0)HEXANE-2-CARBOXAMIDE, N-((1S)-1-(2-(CYCLOPROPYLAMINO)-2- OXOACETYL)PENTYL)-3-((2S)-2-((((1-(((1,1-DIMETHYLETHYL)SULFONYL)METHYL)CYCLOHEXYL) AMINO)CARBONYL)AMINO)-3,3-DIMETHYL-1-OXOBUTYL)-6,6-DIMETHYL-, (1R,2S,5S)-

Common Name

English

narlaprevir [INN]

Common Name

English

SCH 900518

Code

English

Narlaprevir [WHO-DD]

Common Name

English

Code System Code Type Description

CAS

865466-24-6