Danoprevir

Danoprevir (INN)[1] is an orally available[2] 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease.[3] It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC₅₀ = 0.2–0.4 nM; replicon GT1b, EC₅₀ = 1.6 nM).[4]

Danoprevir

Clinical data
Other names	ITMN-191, RG-7227
ATC code	None
Legal status
Legal status	Investigational
Identifiers
IUPAC name (2R,6S,12Z,13aS,14aR,16aS)-6-[(tert-Butoxycarbonyl)amino]-14a-[N-(cyclopropanesulfonyl)carbamoyl]-5,16-dioxo- 1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl 4-fluoro-1,3-dihydro-2H-isoindole-2-carboxylate
CAS Number	850876-88-9
PubChem CID	56841889
ChemSpider	9460579
UNII	911Z9PCQ5F
KEGG	D09884
ChEMBL	ChEMBL2311191
NIAID ChemDB	488730
PDB ligand	TSV (PDBe, RCSB PDB)
Chemical and physical data
Formula	C35H46FN5O9S
Molar mass	731.84 g·mol^−1
3D model (JSmol)
SMILES CC(C)(C)OC(=O)N[C@@H]1CCCCC\C=C/[C@@H]2C[C@]2(NC(=O)[C@@H]3C[C@H](CN3C1=O)OC(=O)N4Cc5cccc(F)c5C4)C(=O)NS(=O)(=O)C6CC6
InChI InChI=1S/C35H46FN5O9S/c1-34(2,3)50-32(45)37-27-13-8-6-4-5-7-11-22-17-35(22,31(44)39-51(47,48)24-14-15-24)38-29(42)28-16-23(19-41(28)30(27)43)49-33(46)40-18-21-10-9-12-26(36)25(21)20-40/h7,9-12,22-24,27-28H,4-6,8,13-20H2,1-3H3,(H,37,45)(H,38,42)(H,39,44)/b11-7-/t22-,23-,27-,28+,35-/m1/s1 Key:ZVTDLPBHTSMEJZ-UPZRXNBOSA-N

History

Danaoprevir was initially developed by Array BioPharma then licensed to Roche for further development and commercialization. In 2013, Danoprevir was licensed to Ascletis by Roche for development and production in China under the tradename Ganovo.[5][6]

References

1. "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 64" (PDF). World Health Organization. p. 265. Retrieved 25 February 2017.
2. Deutsch M, Papatheodoridis GV (August 2010). "Danoprevir, a small-molecule NS3/4A protease inhibitor for the potential oral treatment of HCV infection". Current Opinion in Investigational Drugs. 11 (8): 951–63. PMID 20721837.
3. Jiang Y, Andrews SW, Condroski KR, Buckman B, Serebryany V, Wenglowsky S, et al. (March 2014). "Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease". Journal of Medicinal Chemistry. 57 (5): 1753–69. doi:10.1021/jm400164c. PMID 23672640.
4. Levin J, ed. (2015). "7.4.1 Danoprevir (ITMN-191)". Macrocycles in Drug Discovery. Drug Discovery. The Royal Society of Chemistry. doi:10.1039/9781782623113. ISBN 978-1-84973-701-2.
5. Ng E (17 July 2018). "Singapore sovereign wealth fund GIC to invest US$75 million in Chinese drug maker Ascletis' Hong Kong IPO". South China Morning Post. Retrieved 10 Aug 2018.
6. Speights K (21 February 2017). "How High Can Array BioPharma Inc. Stock Go?". The Motley Fool. Retrieved 13 August 2018.

Further reading

Seiwert SD, Andrews SW, Jiang Y, Serebryany V, Tan H, Kossen K, et al. (December 2008). "Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227)". Antimicrobial Agents and Chemotherapy. 52 (12): 4432–41. doi:10.1128/AAC.00699-08. PMC 2592891. PMID 18824605.