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

• ChemBase ID: 386
• Molecular Formular: C37H48N6O5S2
• Molecular Mass: 720.94422
• Monoisotopic Mass: 720.31276067
• 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
• Canonical 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
• 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

NAMES AND DATABASE IDS

Names

• 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
• 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
• Brand Name: Norvir; Norvir Sec
• Synonyms: Abbott 84538; ritonavir; Ritonavir; Norvir; 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-yl]carbamate; Ritonavir; (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 Ester; A 84538; ABT 538

Database IDs

• CAS Number: 155213-67-5
• MDL Number: MFCD00927142
• PubChem SID: 46505050; 160963849
• PubChem CID: 392622

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.678454
• H Acceptors: 6
• H Donor: 4
• LogD (pH = 5.5): 5.221135
• LogD (pH = 7.4): 5.2217736
• Log P: 5.221782
• Molar Refractivity: 194.5924 cm^3
• Polarizability: 75.68044 Å^3
• Polar Surface Area: 145.78 Å^2
• Rotatable Bonds: 18
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.24
• LOG S: -5.76
• Solubility (Water): 1.26e-03 g/l

PROPERTIES

Physical Property

• Solubility: Methanol (Slightly); Practically insoluble
• Apperance: White Powder
• Melting Point: 120-122°C
• Hydrophobicity(logP): 3.9; 4.937

Safety Information

• Storage Condition: -20°C; -20°C Freezer

Pharmacology Properties

• Target: HIV protease
• Mechanism of Action: HIV-1 protease inhibitor

Product Information

• Purity: 95%
• Salt Data: Free Base
• Application(s): Antiviral agent; Used to treat HIV infection and AIDS

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]

Toronto Research Chemicals - R535000

A selective HIV protease inhibitor.

REFERENCES

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