Vicriviroc maleate

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206617

CAS#: 599179-03-0 (maleate)

Description: Vicriviroc, also known as SCH 417690 and SCH-D, is a potent, orally active and selective CCR5 entry inhibitor of HIV-1. Vicriviroc is effective at nanomolar concentrations, it can be administered once daily. Vicriviroc binds to a small hydrophobic pocket between the transmembrane helices near the extracellular surface of the CCR5 receptor. Binding to this pocket induces a conformational change of the extracellular segment of CCR5 and prevents binding of gp120 to the target cell, consequently preventing the virus from entering the target cell at all.


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Vicriviroc maleate is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206617
Name: Vicriviroc maleate
CAS#: 599179-03-0 (maleate)
Chemical Formula: C32H42F3N5O6
Exact Mass:
Molecular Weight: 649.7122
Elemental Analysis: C, 59.16; H, 6.52; F, 8.77; N, 10.78; O, 14.77


Related CAS #: 599179-03-0 (maleate)   541503-48-4 (HCl)   306296-47-9 (free base)    

Synonym: SCH 417690; SCH-417690; SCH417690; SCH-D; Vicriviroc maleate

IUPAC/Chemical Name: (4,6-dimethylpyrimidin-5-yl)(4-((S)-4-((R)-2-methoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-3-methylpiperazin-1-yl)-4-methylpiperidin-1-yl)methanone maleate

InChi Key: GXINKQQWHLIBJA-UCIBKFKQSA-N

InChi Code: InChI=1S/C28H38F3N5O2.C4H4O4/c1-19-16-35(14-15-36(19)24(17-38-5)22-6-8-23(9-7-22)28(29,30)31)27(4)10-12-34(13-11-27)26(37)25-20(2)32-18-33-21(25)3;5-3(6)1-2-4(7)8/h6-9,18-19,24H,10-17H2,1-5H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,24-;/m0./s1

SMILES Code: CC1(N2C[C@H](C)N([C@H](C3=CC=C(C(F)(F)F)C=C3)COC)CC2)CCN(C(C4=C(C)N=CN=C4C)=O)CC1.O=C(O)/C=C\C(O)=O


Technical Data

Appearance:
White to beige solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
2934.99.90.01


Additional Information

Related CAS#
CAS#599179-03-0 (Vicriviroc maleate)
CAS#541503-48-4 (Vicriviroc HCl)
CAS#306296-47-9 (Vicriviroc free base)

It was developed by the pharmaceutical company Schering-Plough. Merck decided to not pursue regulatory approval for use in treatment-experienced patients because the drug did not meet primary efficacy endpoints in late stage trials. Clinical trials continue in patients previously untreated for HIV.


References

1: Hesk D, Borges S, Hendershot S, Koharski D, McNamara P, Ren S, Saluja S, Truong V, Voronin K. Synthesis of (3) H, (2) H4 and (14) C-SCH 417690 (Vicriviroc). J Labelled Comp Radiopharm. 2016 May 15;59(5):190-6. doi: 10.1002/jlcr.3387. Epub 2016 Mar 14. PubMed PMID: 26991320.

2: Asin-Milan O, Chamberland A, Wei Y, Haidara A, Sylla M, Tremblay CL. Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance. AIDS Res Ther. 2013 Jun 7;10(1):15. doi: 10.1186/1742-6405-10-15. PubMed PMID: 23758814; PubMed Central PMCID: PMC3700831.

3: McNicholas P, Vilchez RA, Greaves W, Kumar S, Onyebuchi C, Black T, Strizki JM. Detection of HIV-1 CXCR4 tropism and resistance in treatment experienced subjects receiving CCR5 antagonist-Vicriviroc. J Clin Virol. 2012 Oct;55(2):134-9. doi: 10.1016/j.jcv.2012.06.021. Epub 2012 Jul 21. PubMed PMID: 22824230.

4: Caseiro MM, Nelson M, Diaz RS, Gathe J, de Andrade Neto JL, Slim J, Solano A, Netto EM, Mak C, Shen J, Greaves W, Dunkle LM, Vilchez RA, Zeinecker J. Vicriviroc plus optimized background therapy for treatment-experienced subjects with CCR5 HIV-1 infection: final results of two randomized phase III trials. J Infect. 2012 Oct;65(4):326-35. doi: 10.1016/j.jinf.2012.05.008. Epub 2012 May 24. PubMed PMID: 22634184.

5: Tsibris AM, Hu Z, Paredes R, Leopold KE, Putcharoen O, Schure AL, Mazur N, Coakley E, Su Z, Gulick RM, Kuritzkes DR. Vicriviroc resistance decay and relative replicative fitness in HIV-1 clinical isolates under sequential drug selection pressures. J Virol. 2012 Jun;86(12):6416-26. doi: 10.1128/JVI.00286-12. Epub 2012 Apr 4. PubMed PMID: 22491471; PubMed Central PMCID: PMC3393533.

6: Berro R, Klasse PJ, Jakobsen MR, Gorry PR, Moore JP, Sanders RW. V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc. Virology. 2012 Jun 5;427(2):158-65. doi: 10.1016/j.virol.2012.02.006. Epub 2012 Mar 16. Erratum in: Virology. 2012 Jun 20;428(1):76. Jakobsen, Martin R [added]; Gorry, Paul R [added]. PubMed PMID: 22424737; PubMed Central PMCID: PMC3320651.

7: Kasserra C, Li J, March B, O'Mara E. Effect of vicriviroc with or without ritonavir on oral contraceptive pharmacokinetics: a randomized, open-label, parallel-group, fixed-sequence crossover trial in healthy women. Clin Ther. 2011 Oct;33(10):1503-14. doi: 10.1016/j.clinthera.2011.08.012. Epub 2011 Oct 19. PubMed PMID: 22015327.

8: Kasserra C, O'Mara E. Pharmacokinetic interaction of vicriviroc with other antiretroviral agents: results from a series of fixed-sequence and parallel-group clinical trials. Clin Pharmacokinet. 2011 Apr;50(4):267-80. doi: 10.2165/11584560-000000000-00000. PubMed PMID: 21348539.

9: McNicholas PM, Mann PA, Wojcik L, Phd PQ, Lee E, McCarthy M, Shen J, Black TA, Strizki JM. Mapping and characterization of vicriviroc resistance mutations from HIV-1 isolated from treatment-experienced subjects enrolled in a phase II study (VICTOR-E1). J Acquir Immune Defic Syndr. 2011 Mar 1;56(3):222-9. doi: 10.1097/QAI.0b013e3181ff63ee. PubMed PMID: 21209592.

10: Lenz JC, Rockstroh JK. Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges. Expert Opin Drug Metab Toxicol. 2010 Sep;6(9):1139-50. doi: 10.1517/17425255.2010.510833. Review. PubMed PMID: 20712521.

11: Wilkin TJ, Su Z, Krambrink A, Long J, Greaves W, Gross R, Hughes MD, Flexner C, Skolnik PR, Coakley E, Godfrey C, Hirsch M, Kuritzkes DR, Gulick RM. Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr. 2010 Aug;54(5):470-6. PubMed PMID: 20672447; PubMed Central PMCID: PMC2917795.

12: Kasserra C, Sansone-Parsons A, Keung A, Tetteh E, Assaf M, O'Mara E, Marbury T. Renal insufficiency has no effect on the pharmacokinetics of vicriviroc in a ritonavir-containing regimen. Clin Pharmacokinet. 2010 Jun;49(6):397-406. doi: 10.2165/11319470-000000000-00000. PubMed PMID: 20481650.

13: Yeh TM, Evans SR, Gulick RM, Clifford DB. Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211. HIV Clin Trials. 2010 Jan-Feb;11(1):51-8. doi: 10.1310/hct1101-51. PubMed PMID: 20400411; PubMed Central PMCID: PMC2958041.

14: McNicholas P, Wei Y, Whitcomb J, Greaves W, Black TA, Tremblay CL, Strizki JM. Characterization of emergent HIV resistance in treatment-naive subjects enrolled in a vicriviroc phase 2 trial. J Infect Dis. 2010 May 15;201(10):1470-80. doi: 10.1086/652189. PubMed PMID: 20373959.

15: O'Mara E, Kasserra C, Huddlestone JR, Wan Y, Soni P, Caceres M, Medlock M, Morrison R, Devinsky O. Effect of vicriviroc on the QT/corrected QT interval and central nervous system in healthy subjects. Antimicrob Agents Chemother. 2010 Jun;54(6):2448-54. doi: 10.1128/AAC.01447-09. Epub 2010 Mar 29. PubMed PMID: 20350942; PubMed Central PMCID: PMC2876383.

16: Disappointing results for vicriviroc. AIDS Patient Care STDS. 2010 Mar;24(3):197-8. PubMed PMID: 20238442.

17: Ogert RA, Hou Y, Ba L, Wojcik L, Qiu P, Murgolo N, Duca J, Dunkle LM, Ralston R, Howe JA. Clinical resistance to vicriviroc through adaptive V3 loop mutations in HIV-1 subtype D gp120 that alter interactions with the N-terminus and ECL2 of CCR5. Virology. 2010 Apr 25;400(1):145-55. doi: 10.1016/j.virol.2010.01.037. Epub 2010 Feb 21. PubMed PMID: 20172579.

18: Crawford KW, Li C, Keung A, Su Z, Hughes MD, Greaves W, Kuritzkes D, Gulick R, Flexner C; ACTG A5211 Study Team. Pharmacokinetic/pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist Vicriviroc in treatment experienced HIV-infected subjects (ACTG protocol 5211). J Acquir Immune Defic Syndr. 2010 Apr;53(5):598-605. doi: 10.1097/QAI.0b013e3181c9caac. PubMed PMID: 20071999; PubMed Central PMCID: PMC2862681.

19: Suleiman J, Zingman BS, Diaz RS, Madruga JV, DeJesus E, Slim J, Mak C, Lee E, McCarthy MC, Dunkle LM, Walmsley S. Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial. J Infect Dis. 2010 Feb 15;201(4):590-9. doi: 10.1086/650342. PubMed PMID: 20064072.

20: Long-term data on vicriviroc released. AIDS Patient Care STDS. 2009 Nov;23(11):989. PubMed PMID: 19938348.