N-{3-[(1R)-1-[(2R)-6-hydroxy-4-oxo-2-(2-phenylethyl)-2-propyl-3,4-dihydro-2H-pyran-5-yl]propyl]phenyl}-5-(trifluoromethyl)pyridine-2-sulfonamide

• ChemBase ID: 808
• Molecular Formular: C31H33F3N2O5S
• Molecular Mass: 602.6643296
• Monoisotopic Mass: 602.20622783
• SMILES: S(=O)(=O)(Nc1cc([C@H](C2=C(O[C@@](CC2=O)(CCc2ccccc2)CCC)O)CC)ccc1)c1ncc(cc1)C(F)(F)F
• Canonical SMILES: CCC[C@@]1(CCc2ccccc2)CC(=O)C(=C(O1)O)[C@@H](c1cccc(c1)NS(=O)(=O)c1ccc(cn1)C(F)(F)F)CC
• InChI: InChI=1S/C31H33F3N2O5S/c1-3-16-30(17-15-21-9-6-5-7-10-21)19-26(37)28(29(38)41-30)25(4-2)22-11-8-12-24(18-22)36-42(39,40)27-14-13-23(20-35-27)31(32,33)34/h5-14,18,20,25,36,38H,3-4,15-17,19H2,1-2H3/t25-,30-/m1/s1
• InChIKey: NZPXPXAGXYTROM-FYBSXPHGSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{3-[(1R)-1-[(2R)-6-hydroxy-4-oxo-2-(2-phenylethyl)-2-propyl-3,4-dihydro-2H-pyran-5-yl]propyl]phenyl}-5-(trifluoromethyl)pyridine-2-sulfonamide
• IUPAC Traditional name: tipranavir
• Brand Name: Aptivus (Boehringer Ingelheim); Aptivus
• Synonyms: TPV; tipranavir; Tipranavir

Database IDs

• CAS Number: 174484-41-4
• PubChem SID: 46506257; 160964271
• PubChem CID: 65027; 54682461

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.956316
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 7.7004013
• LogD (pH = 7.4): 6.8403435
• Log P: 7.8143587
• Molar Refractivity: 163.5574 cm^3
• Polarizability: 59.20148 Å^3
• Polar Surface Area: 105.59 Å^2
• Rotatable Bonds: 11
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.71
• LOG S: -6.46
• Solubility (Water): 2.07e-04 g/l

PROPERTIES

Physical Property

• Solubility: Insoluble
• Hydrophobicity(logP): 6.9

DETAILS

DrugBank - DB00932

• Drug Groups: approved; investigational
• Description: Tipranavir is a sulfonamide-containing dyhydropyrone and a nonpeptidic protease inhibitor that targets the HIV protease. It is administered with ritonavir in combination therapy to treat HIV infections.
• Indication: For combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors.
• Pharmacology: Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. 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. Nelfinavir 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: Oral LD₅₀ in rat is over 5,000 mg/kg. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
• Affected Organisms: Human Immunodeficiency Virus
• Biotransformation: Hepatic. In vitro metabolism studies with human liver microsomes indicated that CYP 3A4 is the predominant CYP enzyme involved in tipranavir metabolism.
• Absorption: Absorption is limited, although no absolute quantification of absorption is available.
• Half Life: 5-6 hours
• Protein Binding: Extensive (> 99.9%), to both human serum albumin and α-1-acid glycoprotein.
• References: Doyon L, Tremblay S, Bourgon L, Wardrop E, Cordingley MG: Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res. 2005 Oct;68(1):27-35. [Pubmed] ; Tipranavir: PNU 140690, tipranivir. Drugs R D. 2006;7(1):55-62. [Pubmed] ; Temesgen Z, Feinberg J: Tipranavir: a new option for the treatment of drug-resistant HIV infection. Clin Infect Dis. 2007 Sep 15;45(6):761-9. Epub 2007 Aug 7. [Pubmed] ; Luna B, Townsend MU: Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance. Clin Ther. 2007 Nov;29(11):2309-18. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Doyon L, Tremblay S, Bourgon L, Wardrop E, Cordingley MG: Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res. 2005 Oct;68(1):27-35. Pubmed
• Tipranavir: PNU 140690, tipranivir. Drugs R D. 2006;7(1):55-62. Pubmed
• Temesgen Z, Feinberg J: Tipranavir: a new option for the treatment of drug-resistant HIV infection. Clin Infect Dis. 2007 Sep 15;45(6):761-9. Epub 2007 Aug 7. Pubmed
• Luna B, Townsend MU: Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance. Clin Ther. 2007 Nov;29(11):2309-18. Pubmed