N-(2/'-C-Methyl-6-O-Methyl-P-1-naphthalenyl-5/'-guanylyl)-L-alanine 2,2-diMethylpropyl ester

• CAT Number: M073485
• CAS Number: 1234490-83-5
• Molecular Formula: C30H39N6O9P
• Molecular Weight: 658.649
• Purity: ≥95%
• Target: RNA-directed RNA polymerase (NS5B) inhibitor
• Storage: Store at -20C
• IUPAC Name: 2,2-dimethylpropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
• InChI: InChI=1S/C30H39N6O9P/c1-17(26(38)42-15-29(2,3)4)35-46(40,45-20-13-9-11-18-10-7-8-12-19(18)20)43-14-21-23(37)30(5,39)27(44-21)36-16-32-22-24(36)33-28(31)34-25(22)41-6/h7-13,16-17,21,23,27,37,39H,14-15H2,1-6H3,(H,35,40)(H2,31,33,34)/t17-,21+,23+,27+,30+,46?/m0/s1
• InChIKey: YFXGICNMLCGLHJ-RSKRLRQZSA-N
• SMILES: CC(C(=O)OCC(C)(C)C)NP(=O)(OCC1C(C(C(O1)N2C=NC3=C2N=C(N=C3OC)N)(C)O)O)OC4=CC=CC5=CC=CC=C54

INX 08189 is an RNA-directed RNA polymerase (NS5B) inhibitor potentially for the treatment of HCV infection.

Reference

1: McGuigan C, Madela K, Aljarah M, Gilles A, Brancale A, Zonta N, Chamberlain S, Vernachio J, Hutchins J, Hall A, Ames B, Gorovits E, Ganguly B, Kolykhalov A, Wang J, Muhammad J, Patti JM, Henson G. Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4850-4. doi: 10.1016/j.bmcl.2010.06.094. PubMed PMID: 20637609.2: Vernachio JH, Bleiman B, Bryant KD, Chamberlain S, Hunley D, Hutchins J, Ames B, Gorovits E, Ganguly B, Hall A, Kolykhalov A, Liu Y, Muhammad J, Raja N, Walters CR, Wang J, Williams K, Patti JM, Henson G, Madela K, Aljarah M, Gilles A, McGuigan C. INX-08189, a phosphoramidate prodrug of 6-O-methyl-2/’-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob Agents Chemother. 2011 May;55(5):1843-51. doi: 10.1128/AAC.01335-10. PubMed PMID: 21357300; PubMed Central PMCID: PMC3088254.3: Yeo KL, Chen YL, Xu HY, Dong H, Wang QY, Yokokawa F, Shi PY. Synergistic suppression of dengue virus replication using a combination of nucleoside analogs and nucleoside synthesis inhibitors. Antimicrob Agents Chemother. 2015 Apr;59(4):2086-93. doi: 10.1128/AAC.04779-14. PubMed PMID: 25624323; PubMed Central PMCID: PMC4356831.4: Gentile I, Buonomo AR, Zappulo E, Borgia G. Discontinued drugs in 2012 – 2013: hepatitis C virus infection. Expert Opin Investig Drugs. 2015 Feb;24(2):239-51. doi: 10.1517/13543784.2015.982274. PubMed PMID: 25384989.5: Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Zennou V, Otto MJ, Furman PA. Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA. J Virol. 2011 Dec;85(23):12334-42. doi: 10.1128/JVI.05639-11. PubMed PMID: 21957306; PubMed Central PMCID: PMC3209386.6: Feng JY, Xu Y, Barauskas O, Perry JK, Ahmadyar S, Stepan G, Yu H, Babusis D, Park Y, McCutcheon K, Perron M, Schultz BE, Sakowicz R, Ray AS. Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus. Antimicrob Agents Chemother. 2015 Nov 23;60(2):806-17. doi: 10.1128/AAC.01922-15. PubMed PMID: 26596942; PubMed Central PMCID: PMC4750701.7: Liu A, Lute J, Gu H, Wang B, Trouba KJ, Arnold ME, Aubry AF, Wang J. Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites including a highly polar, active nucleoside triphosphate in plasma and tissues using LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Sep 1;1000:29-40. doi: 10.1016/j.jchromb.2015.07.006. PubMed PMID: 26209768.8: Ahmad T, Yin P, Saffitz J, Pockros PJ, Lalezari J, Shiffman M, Freilich B, Zamparo J, Brown K, Dimitrova D, Kumar M, Manion D, Heath-Chiozzi M, Wolf R, Hughes E, Muir AJ, Hernandez AF. Cardiac dysfunction associated with a nucleotide polymerase inhibitor for treatment of hepatitis C. Hepatology. 2015 Aug;62(2):409-16. doi: 10.1002/hep.27488. PubMed PMID: 25251156.9: Furman PA, Murakami E, Niu C, Lam AM, Espiritu C, Bansal S, Bao H, Tolstykh T, Micolochick Steuer H, Keilman M, Zennou V, Bourne N, Veselenak RL, Chang W, Ross BS, Du J, Otto MJ, Sofia MJ. Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661. Antiviral Res. 2011 Aug;91(2):120-32. doi: 10.1016/j.antiviral.2011.05.003. PubMed PMID: 21600932; PubMed Central PMCID: PMC3135787.