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Danoprevir

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Medication

Pharmaceutical compound

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
PubChemCID	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

Danoprevir (INN)^[1] is an orally available^[2] 15-membered macrocyclic peptidomimetic inhibitor ofNS3/4A HCV protease.^[3] It containsacylsulfonamide, fluoroisoindole andtert-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 has been evaluated in an open-label, single arm clinical trial in combination withritonavir for treatingCOVID-19^[5] and favourably compared tolopinavir/ritonavir in a second trial.^[6]

History

[edit]

Danoprevir was initially developed byArray BioPharma then licensed to Roche for further development and commercialization. In 2013, Danoprevir was licensed to Ascletis byRoche for development and production in China under the tradename Ganovo.^[7]^[8]

References

[edit]

^"International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 64"(PDF). World Health Organization. p. 265. Retrieved25 February 2017.
^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.
^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.
^Levin J, ed. (2015). "7.4.1 Danoprevir (ITMN-191)".Macrocycles in Drug Discovery. The Royal Society of Chemistry.doi:10.1039/9781782623113.ISBN 978-1-84973-701-2.
^Chen H, Zhang Z, Wang L, Huang Z, Gong F, Li X; et al. (2020)."First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients".Medicine (Baltimore).99 (48): e23357.doi:10.1097/MD.0000000000023357.PMC 7710192.PMID 33235105.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Zhang Z, Wang S, Tu X, Peng X, Huang Y, Wang L; et al. (2020)."A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19".J Med Virol.92 (11):2631–2636.doi:10.1002/jmv.26141.PMC 7300667.PMID 32501538.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^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. Retrieved10 Aug 2018.
^Speights K (21 February 2017)."How High Can Array BioPharma Inc. Stock Go?".The Motley Fool. Retrieved13 August 2018.

NS3/4A protease inhibitors (–previr)	Asunaprevir Boceprevir^‡ Ciluprevir^§ Danoprevir^† Faldaprevir^‡ Glecaprevir Grazoprevir Narlaprevir Paritaprevir Simeprevir Sovaprevir^† Telaprevir^‡ Vaniprevir Vedroprevir^§ Voxilaprevir
NS5A inhibitors (–asvir)	Coblopasvir Daclatasvir^# Elbasvir Ledipasvir Odalasvir^† Ombitasvir Pibrentasvir Ravidasvir^† Ruzasvir^† Samatasvir^† Velpatasvir
NS5B RNA polymerase inhibitors (–buvir)	Beclabuvir^† Bemnifosbuvir^† Dasabuvir^# Deleobuvir^§ Filibuvir^§ GS-6620^§ IDX-184^§ Setrobuvir^§ Sofosbuvir^# Tegobuvir^§ TMC-647055^§ Radalbuvir^† Uprifosbuvir^†
Combination drugs	Elbasvir/grazoprevir Glecaprevir/pibrentasvir Ledipasvir/sofosbuvir^# Ombitasvir/paritaprevir/ritonavir^# Sofosbuvir/daclatasvir Sofosbuvir/velpatasvir^# Sofosbuvir/velpatasvir/voxilaprevir

Hepatitis D

Bulevirtide

Picornavirus

viral entry:Pleconaril^†

Anti-influenza agents

neuraminidase inhibitors/release phase (Oseltamivir^#
Zanamivir
Peramivir,Laninamivir^†)

Multiple/general

Interferon	Interferon alfa 2b Peginterferon alfa-2a^# Peginterferon alfa-2b^#
3CL protease inhibitors (–trelvir)	Atilotrelvir Ensitrelvir^† Ibuzatrelvir Leritrelvir Lufotrelvir Nirmatrelvir^† (+ritonavir)^† Rupintrivir Simnotrelvir (+ritonavir^†)
RNA pol inhibitors	CMX521^§ Deuremidevir^† Favipiravir Galidesivir^† GS-441524^§ Remdesivir MK-608^§ Mericitabine^† Molnupiravir NITD008^§ Ribavirin^# Taribavirin^† Triazavirin Valopicitabine^†
Multiple/Unknown/Other	EICAR^§ Merimepodib^§ Moroxydine Presatovir^†