GS-6620

GS-6620 is an antiviral drug which is a nucleotide analogue. It was developed for the treatment of Hepatitis C but while it showed potent antiviral effects in early testing,[1][2] it could not be successfully formulated into an oral dosage form due to low and variable absorption in the intestines which made blood levels unpredictable.[3][4] It has however continued to be researched as a potential treatment for other viral diseases such as Ebola virus disease.[5][6]

GS-6620
Clinical data
Trade namesGS-6620
Legal status
Legal status
Identifiers
IUPAC name
  • [(2R,3R,4R,5R)-5-(4-Aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-4-hydroxy-4-methyl-2-[[[[(2S)-1-oxo-1-propan-2-yloxypropan-2-yl]amino]-phenoxyphosphoryl]oxymethyl]oxolan-3-yl] 2-methylpropanoate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC29H37N6O9P
Molar mass644.6 g·mol−1
3D model (JSmol)
SMILES
  • C[C@@H](C(=O)OC(C)C)NP(=O)(OC[C@@H]1[C@H]([C@@]([C@](O1)(C#N)C2=CC=C3N2N=CN=C3N)(C)O)OC(=O)C(C)C)OC4=CC=CC=C4
InChI
  • InChI=1S/C29H37N6O9P/c1-17(2)26(36)42-24-22(43-29(15-30,28(24,6)38)23-13-12-21-25(31)32-16-33-35(21)23)14-40-45(39,44-20-10-8-7-9-11-20)34-19(5)27(37)41-18(3)4/h7-13,16-19,22,24,38H,14H2,1-6H3,(H,34,39)(H2,31,32,33)/t19-,22+,24+,28+,29-,45?/m0/s1
  • Key:YAAQYJCOIFNMKX-CVANIGNKSA-N

References
  1. Cho A, Zhang L, Xu J, Lee R, Butler T, Metobo S, et al. (March 2014). "Discovery of the first C-nucleoside HCV polymerase inhibitor (GS-6620) with demonstrated antiviral response in HCV infected patients". Journal of Medicinal Chemistry. 57 (5): 1812–25. doi:10.1021/jm400201a. PMID 23547794.
  2. Feng JY, Cheng G, Perry J, Barauskas O, Xu Y, Fenaux M, et al. (2014). "Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug". Antimicrobial Agents and Chemotherapy. 58 (4): 1930–42. doi:10.1128/AAC.02351-13. PMC 4023746. PMID 24419349.
  3. Murakami E, Wang T, Babusis D, Lepist EI, Sauer D, Park Y, et al. (2014). "Metabolism and pharmacokinetics of the anti-hepatitis C virus nucleotide prodrug GS-6620". Antimicrobial Agents and Chemotherapy. 58 (4): 1943–51. doi:10.1128/AAC.02350-13. PMC 4023801. PMID 24419340.
  4. Gentile I, Coppola N, Buonomo AR, Zappulo E, Borgia G (September 2014). "Investigational nucleoside and nucleotide polymerase inhibitors and their use in treating hepatitis C virus". Expert Opinion on Investigational Drugs. 23 (9): 1211–23. doi:10.1517/13543784.2014.921680. PMID 24848437. S2CID 12115460.
  5. De Clercq E (March 2016). "C-Nucleosides To Be Revisited". Journal of Medicinal Chemistry. 59 (6): 2301–11. doi:10.1021/acs.jmedchem.5b01157. PMID 26513594.
  6. De Clercq E (November 2019). "New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections". Chemistry: An Asian Journal. 14 (22): 3962–3968. doi:10.1002/asia.201900841. PMC 7159701. PMID 31389664.


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