CAS 473921-12-9|Lersivirine

Introduction：Basic information about CAS 473921-12-9|Lersivirine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Lersivirine BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	Lersivirine
CAS Number	473921-12-9	Molecular Weight	310.350
Density	1.2±0.1 g/cm3	Boiling Point	455.4±45.0 °C at 760 mmHg
Molecular Formula	C₁₇H₁₈N₄O₂	Melting Point	/
MSDS	/	Flash Point	229.2±28.7 °C

Names

Name	5-[3,5-diethyl-1-(2-hydroxyethyl)pyrazol-4-yl]oxybenzene-1,3-dicarbonitrile
Synonym	More Synonyms

Lersivirine BiologicalActivity

Description	Lersivirine(UK-453061) is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI, IC50=119 nM) with a unique resistance profile that exhibits potent antiretroviral activity against wild-type human immunodeficiency virus and clinically relevant NNRTI-resistant strains.IC50 value: 0.119 uM [1]Target: NNRTIUK-453061(Compound 5) demonstrated excellent activity against large panels of wild type and drug-resistant HIV consistent with the encouraging profile demonstrated against the isolated RT enzymes. Compound 5 can be readily prepared in multi-gram quantities by virtue of the efficient and concise synthetic route. The compound also has good aqueous solubility and formulation characteristics which enable further in vivo evaluation. Clinical trials evaluating the potential of 5 (UK-453,061, lersivirine) to treat HIV infection are proceeding and further progress will be reported in due course [1].At clinically relevant lersivirine doses (500-1,000 mg total daily dose), the mean plasma exposure of midazolam was reduced in a dose-dependent manner by 20-36 %. Co-administration of lersivirine 1,000 mg QD with OCs had minor PK effects, increasing ethinylestradiol exposure by 10 % and reducing levonorgestrel exposure by 13 % [2]. Mated Crl:CD1(ICR) mice were administered 0, 150, 350, and 500 mg/kg lersivirine once daily by oral gavage on gestation days 6 to 17, followed by cesarean section on gestation day 18. The first 2 days of dosing for the high-dose group were done at 250 mg/kg to allow induction of hepatic metabolizing enzymes, after which the dose was increased to 500 mg/kg/day [3].
Related Catalog	Signaling Pathways >>Anti-infection >>HIVSignaling Pathways >>Anti-infection >>Reverse TranscriptaseResearch Areas >>Infection
References	[1]. Mowbray CE, et al. Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development candidate. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5857-60. [2]. Davis J, et al. The effect of lersivirine, a next-generation NNRTI, on the pharmacokinetics of midazolam and oral contraceptives in healthy subjects. Eur J Clin Pharmacol. 2012 Nov;68(11):1567-72. [3]. Cappon GD, et al. Developmental toxicity study of lersivirine in mice. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):225-30.

Description

Lersivirine(UK-453061) is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI, IC50=119 nM) with a unique resistance profile that exhibits potent antiretroviral activity against wild-type human immunodeficiency virus and clinically relevant NNRTI-resistant strains.IC50 value: 0.119 uM [1]Target: NNRTIUK-453061(Compound 5) demonstrated excellent activity against large panels of wild type and drug-resistant HIV consistent with the encouraging profile demonstrated against the isolated RT enzymes. Compound 5 can be readily prepared in multi-gram quantities by virtue of the efficient and concise synthetic route. The compound also has good aqueous solubility and formulation characteristics which enable further in vivo evaluation. Clinical trials evaluating the potential of 5 (UK-453,061, lersivirine) to treat HIV infection are proceeding and further progress will be reported in due course [1].At clinically relevant lersivirine doses (500-1,000 mg total daily dose), the mean plasma exposure of midazolam was reduced in a dose-dependent manner by 20-36 %. Co-administration of lersivirine 1,000 mg QD with OCs had minor PK effects, increasing ethinylestradiol exposure by 10 % and reducing levonorgestrel exposure by 13 % [2]. Mated Crl:CD1(ICR) mice were administered 0, 150, 350, and 500 mg/kg lersivirine once daily by oral gavage on gestation days 6 to 17, followed by cesarean section on gestation day 18. The first 2 days of dosing for the high-dose group were done at 250 mg/kg to allow induction of hepatic metabolizing enzymes, after which the dose was increased to 500 mg/kg/day [3].

Related Catalog

Signaling Pathways >>Anti-infection >>HIVSignaling Pathways >>Anti-infection >>Reverse TranscriptaseResearch Areas >>Infection

References

[1]. Mowbray CE, et al. Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development candidate. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5857-60.

[2]. Davis J, et al. The effect of lersivirine, a next-generation NNRTI, on the pharmacokinetics of midazolam and oral contraceptives in healthy subjects. Eur J Clin Pharmacol. 2012 Nov;68(11):1567-72.

[3]. Cappon GD, et al. Developmental toxicity study of lersivirine in mice. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):225-30.

Chemical & Physical Properties

Density	1.2±0.1 g/cm3
Boiling Point	455.4±45.0 °C at 760 mmHg
Molecular Formula	C₁₇H₁₈N₄O₂
Molecular Weight	310.350
Flash Point	229.2±28.7 °C
Exact Mass	310.142975
PSA	94.86000
LogP	3.30
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.595
InChIKey	MCPUZZJBAHRIPO-UHFFFAOYSA-N
SMILES	CCc1nn(CCO)c(CC)c1Oc1cc(C#N)cc(C#N)c1
Storage condition	2-8℃

Synonyms

ZZE

Lersivirine [USAN:INN]

1,3-Benzenedicarbonitrile, 5-((3,5-diethyl-1-(2- hydroxyethyl)-1H-pyrazol-4-yl)oxy)-

3-CYANO-5-[[3,5-DIETHYL-1-(2-HYDROXYETHYL)-1H-PYRAZOL-4-YL]OXY]BENZONITRILE

Lersivirine

5-{[3,5-Diethyl-1-(2-Hydroxyethyl)-1h-Pyrazol-4-Yl]oxy}benzene-1,3-Dicarbonitrile

5-{[3,5-Diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl]oxy}isophthalonitrile

1,3-Benzenedicarbonitrile, 5-[[3,5-diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4-yl]oxy]-

2won

5-((3,5-Diethyl-1-(2-hydroxyethyl)-1H-pyrazol-4- yl)oxy)benzene-1,3-dicarbonitrile

[14C]-Lersivirine

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