MedKoo Cat#: 314271
Name: Tenofovir alafenamide fumarate (1:1 salt)
CAS#: 379270-38-9 (fumarate)
Chemical Formula: C25H33N6O9P
Exact Mass:
Molecular Weight: 593.55
Elemental Analysis: C, 50.68; H, 5.61; N, 14.18; O, 24.30; P, 5.23
Related CAS #: 379270-38-9 (fumarate) 1392275-56-7 (hemifumarate) 379270-37-8 (free base)
Synonym: TAF; GS734; GS-734; GS 7340; Tenofovir alafenamide fumarate; trade name: Genvoya.
IUPAC/Chemical Name: (S)-isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate fumarate
InChi Key: MEJAFWXKUKMUIR-WIUYAKJJSA-N
InChi Code: InChI=1S/C21H29N6O5P.C4H4O4/c1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27;5-3(6)1-2-4(7)8/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24);1-2H,(H,5,6)(H,7,8)/b;2-1+/t15-,16+,33?;/m1./s1
SMILES Code: C[C@@H](C(OC(C)C)=O)N[P@@](OC1=CC=CC=C1)(CO[C@@H](CN2C=NC3=C(N=CN=C23)N)C)=O.O=C(/C=C/C(O)=O)O
Technical Data
View CoA: previous batch, Lot#TZC51228
NMR comparison of Tenofovir alafenamide derivatives: free base; hemifumarate salt and fumarate salt
View QC data: current batch, Lot#BBC70118
Additional Information
Related CAS#
CAS#379270-38-9 =Tenofovir alafenamide fumarate, 1:1
CAS#1392275-56-7= Tenofovir alafenamide hemifumarate, 2:1
CAS#379270-37-8 = Tenofovir alafenamide
References
1: Majewska A, Mlynarczyk-Bonikowska B, Malejczyk M, Mlynarczyk G, Majewski S. Antiviral Medication in Sexually Transmitted Diseases. Part II: HIV. Mini Rev Med Chem. 2015;15(2):93-103. PubMed PMID: 25751258.
2: Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, Wang H, Callebaut C, Martin H, Fordyce MW, McCallister S. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. doi: 10.1097/QAI.0000000000000225. PubMed PMID: 24872136.
3: Markowitz M, Zolopa A, Squires K, Ruane P, Coakley D, Kearney B, Zhong L, Wulfsohn M, Miller MD, Lee WA. Phase I/II study of the pharmacokinetics, safety and antiretroviral activity of tenofovir alafenamide, a new prodrug of the HIV reverse transcriptase inhibitor tenofovir, in HIV-infected adults. J Antimicrob Chemother. 2014 May;69(5):1362-9. doi: 10.1093/jac/dkt532. Epub 2014 Feb 6. PubMed PMID: 24508897.
4: Flexner C, Saag M. The antiretroviral drug pipeline: prospects and implications for future treatment research. Curr Opin HIV AIDS. 2013 Nov;8(6):572-8. doi: 10.1097/COH.0000000000000011. Review. PubMed PMID: 24100879.
5: De Clercq E. Dancing with chemical formulae of antivirals: a personal account. Biochem Pharmacol. 2013 Sep 15;86(6):711-25. doi: 10.1016/j.bcp.2013.07.012. Epub 2013 Jul 19. Review. PubMed PMID: 23876344.
6: Ruane PJ, DeJesus E, Berger D, Markowitz M, Bredeek UF, Callebaut C, Zhong L, Ramanathan S, Rhee MS, Fordyce MW, Yale K. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55. doi: 10.1097/QAI.0b013e3182965d45. PubMed PMID: 23807155.
7: De Clercq E. A Cutting-Edge View on the Current State of Antiviral Drug Development. Med Res Rev. 2013 Mar 11. doi: 10.1002/med.21281. [Epub ahead of print] PubMed PMID: 23495004.
8: Saag MS. New and investigational antiretroviral drugs for HIV infection: mechanisms of action and early research findings. Top Antivir Med. 2012 Dec;20(5):162-7. Review. PubMed PMID: 23363694.
9: Permpalung N, Putcharoen O, Avihingsanon A, Ruxrungtham K. Treatment of HIV infection with once-daily regimens. Expert Opin Pharmacother. 2012 Nov;13(16):2301-17. doi: 10.1517/14656566.2012.729040. Epub 2012 Oct 8. Review. PubMed PMID: 23043453.
10: Lepist EI, Phan TK, Roy A, Tong L, Maclennan K, Murray B, Ray AS. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob Agents Chemother. 2012 Oct;56(10):5409-13. doi: 10.1128/AAC.01089-12. Epub 2012 Jul 30. PubMed PMID: 22850510; PubMed Central PMCID: PMC3457391.
11: Llibre JM, Clotet B. Once-daily single-tablet regimens: a long and winding road to excellence in antiretroviral treatment. AIDS Rev. 2012 Jul-Sep;14(3):168-78. Review. PubMed PMID: 22833060.
12: Kersh EN, Luo W, Zheng Q, Adams DR, Hanson D, Youngpairoj AS, Cong ME, Butler K, Hendry RM, McNicholl JM, Heneine W, Garcia-Lerma JG. Reduced inflammation and CD4 loss in acute SHIV infection during oral pre-exposure prophylaxis. J Infect Dis. 2012 Sep 1;206(5):770-9. doi: 10.1093/infdis/jis422. Epub 2012 Jun 27. PubMed PMID: 22740713; PubMed Central PMCID: PMC3491742.
13: Babusis D, Phan TK, Lee WA, Watkins WJ, Ray AS. Mechanism for effective lymphoid cell and tissue loading following oral administration of nucleotide prodrug GS-7340. Mol Pharm. 2013 Feb 4;10(2):459-66. doi: 10.1021/mp3002045. Epub 2012 Jul 12. PubMed PMID: 22738467.
14: Birkus G, Kutty N, He GX, Mulato A, Lee W, McDermott M, Cihlar T. Activation of 9-[(R)-2-[[(S)-[[(S)-1-(Isopropoxycarbonyl)ethyl]amino] phenoxyphosphinyl]-methoxy]propyl]adenine (GS-7340) and other tenofovir phosphonoamidate prodrugs by human proteases. Mol Pharmacol. 2008 Jul;74(1):92-100. doi: 10.1124/mol.108.045526. Epub 2008 Apr 22. PubMed PMID: 18430788.
15: Birkus G, Wang R, Liu X, Kutty N, MacArthur H, Cihlar T, Gibbs C, Swaminathan S, Lee W, McDermott M. Cathepsin A is the major hydrolase catalyzing the intracellular hydrolysis of the antiretroviral nucleotide phosphonoamidate prodrugs GS-7340 and GS-9131. Antimicrob Agents Chemother. 2007 Feb;51(2):543-50. Epub 2006 Dec 4. PubMed PMID: 17145787; PubMed Central PMCID: PMC1797775.
16: Cihlar T. Nucleotide HIV reverse transcriptase inhibitors: tenofovir and beyond. Curr Opin HIV AIDS. 2006 Sep;1(5):373-9. doi: 10.1097/01.COH.0000239849.20828.09. PubMed PMID: 19372836.
17: Van Rompay KK, Kearney BP, Sexton JJ, Colón R, Lawson JR, Blackwood EJ, Lee WA, Bischofberger N, Marthas ML. Evaluation of oral tenofovir disoproxil fumarate and topical tenofovir GS-7340 to protect infant macaques against repeated oral challenges with virulent simian immunodeficiency virus. J Acquir Immune Defic Syndr. 2006 Sep;43(1):6-14. PubMed PMID: 16810108.
18: Lee WA, He GX, Eisenberg E, Cihlar T, Swaminathan S, Mulato A, Cundy KC. Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue. Antimicrob Agents Chemother. 2005 May;49(5):1898-906. PubMed PMID: 15855512; PubMed Central PMCID: PMC1087627.
19: Chapman H, Kernan M, Prisbe E, Rohloff J, Sparacino M, Terhorst T, Yu R. Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):621-8. PubMed PMID: 11563079.
20: Eisenberg EJ, He GX, Lee WA. Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):1091-8. PubMed PMID: 11562963.
