Modulators of pharmacokinetic properties of therapeutics

• US 8,148,374 B2
• Filed: 02/22/2008
• Issued: 04/03/2012
• Est. Priority Date: 02/23/2007
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Desai, Manoj C., Liu, Hongtao, Xu, Lianhong
• Primary Examiner(s): Anderson, Rebecca
• Assistant Examiner(s): Otton, Alicia L
• Application Number:
  US12/036,124
• Publication Number:
  US 20080207620A1
• Time in Patent Office: 1,502 Days
• Field of Search: None
• US Class Current: 514/236.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07D 277/28 Radicals substituted by nitrogen atoms
• CPC Class Codes: C07D 277/30 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: G01N 33/94 involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors

Abstract

The present application provides for a compound of Formula IV,

or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

Claims

1. A compound which is

2. A pharmaceutical composition comprising the compound or salt of claim 1, and a pharmaceutically acceptable carrier or excipient.

3. The pharmaceutical composition of claim 2, further comprising at least one therapeutic agent which is metabolized by cytochrome P450.

4. The pharmaceutical composition of claim 3, wherein the at least one therapeutic agent is selected from the group consisting of HIV protease inhibitors, HIV non-nucleoside inhibitors of reverse transcriptase, HIV nucleoside inhibitors of reverse transcriptase, HIV nucleotide inhibitors of reverse transcriptase, HIV integrase inhibitors, gp41 inhibitors, CXCR4 inhibitors, gp120 inhibitors, G6PD inhibitors, NADH-oxidase inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, other drugs for treating HIV, interferons, ribavirin, NS3 protease inhibitors, alpha-glucosidase 1 inhibitors, hepatoprotectants, non-nucleoside inhibitors of HCV, NS5a inhibitors, NS5b polymerase inhibitors, other drugs for treating HCV, and combinations thereof.

5. A compound which is:

6. A method for inhibiting cytochrome P450 monooxygenase in a patient in need thereof, comprising administering to the patient an amount of the compound

7. The method of claim 6, wherein the cytochrome P450 monooxygenase enzyme that is inhibited is 3A isoenzyme.

8. The method of claim 7, wherein the cytochrome P450 monooxygenase enzyme that is inhibited is 3A4 isoenzyme.

9. The method of claim 8, wherein cytochrome P450 monooxygenase isoenzyme 2C9 is not inhibited or is inhibited substantially less than the 3A4 isoenzyme.

10. The method of claim 7, wherein the compound