CAS 155213-67-5|Norvir Softgel|1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-y...

General Information

Structure

Molecular Formula

C₃₇H₄₈N₆O₅S₂

Molecular Mass

720.94422

Exact Mass

720.31276067

Charge

InChI

InChI=1S/C37H48N6O5S2/c1-24(2)33(42-36(46)43(5)20-29-22-49-35(40-29)25(3)4)34(45)39-28(16-26-12-8-6-9-13-26)18-32(44)31(17-27-14-10-7-11-15-27)41-37(47)48-21-30-19-38-23-50-30/h6-15,19,22-25,28,31-33,44H,16-18,20-21H2,1-5H3,(H,39,45)(H,41,47)(H,42,46)/t28-,31-,32-,33-/m0/s1

InChIKey

NCDNCNXCDXHOMX-XGKFQTDJSA-N

Canonic Smiles

O=C(N[C@H]([C@H](C[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)NC(=O)N(Cc1csc(n1)C(C)C)C)O)Cc1ccccc1)OCc1cncs1

Isomeric Smiles

s1c(nc(CN(C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@@H](NC(=O)OCc2scnc2)Cc2ccccc2)Cc2ccccc2)C)c1)C(C)C

Calculated Properties

JChem

LogD (pH = 7.4)

5.22

LogD (pH = 5.5)

5.22

Log P

5.22

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

false

Acid pKa

2.84

Polar Surface Area

145.78

Polarizability

76.92

Molar Refractivity

194.59

LOG S

-6.24

Data Source

Names and Identifiers

Synonyms

NorvirNorvir SoftgelRitonavir(3S,4S,6S,9S)-4-Hydroxy-12-methyl-9-(1-methylethyl)-13-[2-(1-methylethyl)-4-thiazolyl]-8,11-dioxo-3,6-bis(phenylmethyl)-2,7,10,12-tetraazatridecanoic Acid 5-Thiazolylmethyl EsterA 84538ABT 538ritonavirAbbott 84538Ritonavir1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamateritonavir

IUPAC Traditional name

ritonavir 1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate

IUPAC name

1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate (1,3-thiazol-5-yl)methyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate

Brand Name

NorvirNorvir Sec

API Name

Ritonavir

International Nonproprietary Name (INN)

ritonavir

Names and Identifiers

Registration numbers

CAS Number

155213-67-5

MDL Number

MFCD00927142

PubChem CID

392622

PubChem SID

46505050160963849223438476

DrugBank ID

DB00503

Protein Data Bank

1sh95veu4njv2b603nxu3ndw4eyr6xcy3ndx3q701n491rl83tne3prs5vce5vc01hxw

Reaxys Registry

768009

PubMed Citation Links

24202050119968899585800113633299278209914026511363397856829211363517113630861136330011363184

BRENDA Ligand Database

134732160172523056091333326133918

MassBank Database

EA258004EA258008EA258012EA258002EA258006EA258013EA258005EA258003EA258011EA258014EA258007EA258001EA258010EA258009

LINCS Database

LSM-5623

BKMS React Database

160172609133332613473213391852305

BRENDA Database

7.6.2.23.4.23.B13.4.23.B43.4.23.503.4.23.B33.4.23.16

MetaboLights Database

MTBLS2224MTBLS2871MTBLS1642

CHEMBL

KEGG ID

ACToR Database

SureChEMBL Database

Wikipedia Title

PDBeChem Database

KEGG DRUG Database

HMDB Database

CHEBI ID

CHEBI:8873CHEBI:45409

CompTox Database

DTXSID1048627

Drug Central Database

2,391

Registration numbers

Properties

Safety Information

-20°C

-20°C Freezer

Download link

Pharmacology Properties

HIV protease

HIV-1 protease inhibitor

Properties

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

DrugBank

DB00503

Drug Groups

approved; investigational

Description

An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [PubChem]

Indication

Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.

Pharmacology

Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Ritonavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Toxicity

Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice.

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of ritonavir, however, plasma concentrations are low. The cytochrome P450 enzymes CYP3A and CYP2D6 are primarily involved in the metabolism of ritonavir.

Absorption

The absolute bioavailability of ritonavir has not been determined.

Half Life

3-5 hours

Protein Binding

98-99%

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1185

Research Area: Immunology
Biological Activity:
Ritonavir is an inhibitor of HIV protease used to treat HIV infection and AIDS. It is now rarely used for its own antiviral activity, but remains widely used as a booster of other protease inhibitors. More specifically, ritonavir is used to inhibit a particular liver enzyme that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4). The drug’s molecular structure inhibits CYP3A4, so a low dose can be used to enhance other protease inhibitors. This discovery has drastically reduced the adverse effects and improved the efficacy of PI’s and HAART. [1]

TRC

R535000

A selective HIV protease inhibitor.

ChEBI

CHEBI:45409

An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.

Molecule Details

References

PubChem Literature

From Data Sources

• http://en.wikipedia.org/wiki/Ritonavir

• Daluge, S., et al.: Antimicrob. Agents Chemother., 38, 1590 (1994)

• Harrigan, P., et al.: J. Infect. Dis., 191, 339 (1994)

• Miller, J., et al.: Bioorg. Med. Chem. Lett., 16, 1788(2006)

• Ammaranond, P., et al.: J. Clin. Virol., 26, 153 (1994)

• Kempf, D.J. et al., Proc. Natl. Acad. Sci. U.S.A., 1995, 92, 2484, (pharmacol)

• Leonard, J.M., Adv. Exp. Med. Biol., 1996, 394, 319, (pharmacol, rev)

• Koudriakova, T. et al., Drug Metab. Dispos., 1998, 26, 552-561, (metab)

• Kempf, D.J. et al., J. Med. Chem., 1998, 41, 602-617, (rev)

• Lea, A.P. et al., Drugs, 1996, 52, 541, (rev)

• Danner, S.A. et al., N. Engl. J. Med., 1995, 333, 1528; 1534, (clin trials)

• Markowitz, M. et al., J. Virol., 1995, 69, 701, (pharmacol)

• Pat. Coop. Treaty (WIPO), 1995, Abbott, 95 07 696; CA, 122, 299083, (synth, pharmacol)

• Kumar, G.N. et al., J. Pharmacol. Exp. Ther., 1996, 277, 423, (metab)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

Synonyms

IUPAC Traditional name

ritonavir 1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate

IUPAC name

Brand Name

NorvirNorvir Sec

API Name

Ritonavir

International Nonproprietary Name (INN)

ritonavir

Registration numbers

CAS Number

155213-67-5

MDL Number

MFCD00927142

PubChem CID

392622

PubChem SID

46505050160963849223438476

DrugBank ID

DB00503

Protein Data Bank

1sh95veu4njv2b603nxu3ndw4eyr6xcy3ndx3q701n491rl83tne3prs5vce5vc01hxw

Reaxys Registry

768009

PubMed Citation Links

24202050119968899585800113633299278209914026511363397856829211363517113630861136330011363184

BRENDA Ligand Database

134732160172523056091333326133918

MassBank Database

EA258004EA258008EA258012EA258002EA258006EA258013EA258005EA258003EA258011EA258014EA258007EA258001EA258010EA258009

LINCS Database

LSM-5623

BKMS React Database

160172609133332613473213391852305

BRENDA Database

7.6.2.23.4.23.B13.4.23.B43.4.23.503.4.23.B33.4.23.16

MetaboLights Database

MTBLS2224MTBLS2871MTBLS1642

CHEMBL

KEGG ID

ACToR Database

SureChEMBL Database

Wikipedia Title

PDBeChem Database

KEGG DRUG Database

HMDB Database

CHEBI ID

CHEBI:8873CHEBI:45409

CompTox Database

DTXSID1048627

Drug Central Database

2,391

Molecule Details

DrugBank

DB00503

Drug Groups

approved; investigational

Description

An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [PubChem]

Indication

Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.

Pharmacology

Toxicity

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Absorption

The absolute bioavailability of ritonavir has not been determined.

Half Life

3-5 hours

Protein Binding

98-99%

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1185

TRC

R535000

A selective HIV protease inhibitor.

ChEBI

CHEBI:45409

References

PubChem Literature

From Data Sources

• http://en.wikipedia.org/wiki/Ritonavir

• Daluge, S., et al.: Antimicrob. Agents Chemother., 38, 1590 (1994)

• Harrigan, P., et al.: J. Infect. Dis., 191, 339 (1994)

• Miller, J., et al.: Bioorg. Med. Chem. Lett., 16, 1788(2006)

• Ammaranond, P., et al.: J. Clin. Virol., 26, 153 (1994)

• Kempf, D.J. et al., Proc. Natl. Acad. Sci. U.S.A., 1995, 92, 2484, (pharmacol)

• Leonard, J.M., Adv. Exp. Med. Biol., 1996, 394, 319, (pharmacol, rev)

• Koudriakova, T. et al., Drug Metab. Dispos., 1998, 26, 552-561, (metab)

• Kempf, D.J. et al., J. Med. Chem., 1998, 41, 602-617, (rev)

• Lea, A.P. et al., Drugs, 1996, 52, 541, (rev)

• Danner, S.A. et al., N. Engl. J. Med., 1995, 333, 1528; 1534, (clin trials)

• Markowitz, M. et al., J. Virol., 1995, 69, 701, (pharmacol)

• Pat. Coop. Treaty (WIPO), 1995, Abbott, 95 07 696; CA, 122, 299083, (synth, pharmacol)

• Kumar, G.N. et al., J. Pharmacol. Exp. Ther., 1996, 277, 423, (metab)

Bioactivity

PubChem BioAssay

Properties

Safety Information

-20°C

-20°C Freezer

Download link

Pharmacology Properties

HIV protease

HIV-1 protease inhibitor

Molecule

ID:386