| Identification | Back Directory | [Name]
N-(2'-C-Methyl-6-O-Methyl-P-1-naphthalenyl-5'-guanylyl)-L-alanine 2,2-diMethylpropyl ester | [CAS]
1234490-83-5 | [Synonyms]
INX-189
INX 08189
BMS-986094
INX-08189 BMS 986094
BMS986094,BMS 986094
N-(2'-C-Methyl-6-O-Methyl-P-1-naphthalenyl-5'-guanylyl)-L-alanine 2,2-diMethylpropyl ester
L-Alanine, N-(2'-C-methyl-6-O-methyl-P-1-naphthalenyl-5'-guanylyl)-, 2,2-dimethylpropyl ester
(2S)-Neopentyl 2-(((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yl)phosphoryl)amino)propanoate
(2S)-neopentyl 2-(((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphoryl)amino)propanoate
(2S)-neopentyl 2-(((((2R,3R,4R,5R)-3,4-dihydroxy-5-(2-imino-6-methoxy-2H-purin-9(3H)-yl)-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphoryl)amino)propanoate | [Molecular Formula]
C30H39N6O9P | [MDL Number]
MFCD22124897 | [MOL File]
1234490-83-5.mol | [Molecular Weight]
658.639 |
| Chemical Properties | Back Directory | [Boiling point ]
848.7±75.0 °C(Predicted) | [density ]
1.47 | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
Solid | [pka]
13.01±0.70(Predicted) | [color ]
White to off-white | [InChIKey]
YFXGICNMLCGLHJ-RSKRLRQZSA-N | [SMILES]
[P](=O)(N[C@@H](C)C(=O)OCC(C)(C)C)(OC[C@H]3O[C@H]([C@@]([C@@H]3O)(O)C)[n]4c5[nH][c](nc(c5nc4)OC)=N)Oc1c2c(ccc1)cccc2 |
| Hazard Information | Back Directory | [Uses]
BMS-986094 (INX-08189) is a potent inhibitor of hepatitis C virus (HCV) replication, with an EC50 of 35 nM at 24 h in Huh-7 cells. BMS-986094 is a phosphoramidate proagent of 6-O-methyl-2’-C-methyl guanosine. BMS-986094 can be used for the research of chronic HCV infection[1][2]. | [Biological Activity]
BMS-986094 is an orally available prodrug of nucleotide analogue 2′-C-methylguanosine th at potently inhibits Hepatitis C virus (HCV) replication. It is a guanosine nucleotide inhibitor of HCV RNA-dependent RNA polymerase NS5b. | [in vivo]
BMS-986094 (3-300 mg/kg; p.o.) converts to 2′-C-Me-GTP after oral administration, and 2’-C-MeG in the plasma is proportional to the production of 2’-C-MeGTP in the liver[1].
BMS-986094 (25 mg/kg; p.o.) is efficiently extracts from the portal circulation by the liver following oral administration in cynomolgus monkeys[1].
BMS-986094 (15 or 30 mg/kg/d; p.o. for 3 weeks) administers cynomolgus monkeys, the nucleoside metabolite M2 was the major plasma analyte, and INX-09114 was the highest drug-related species in the heart and kidney[3]. | Animal Model: | Male Sprague-Dawley rats[1] | | Dosage: | 3, 5, 10, 25 mg/kg | | Administration: | A single p.o. administration | | Result: | At doses of ≥5 mg/kg, the concentrations of 2′-C-MeGTP in the liver exceeded the EC90 soon after dosing and remained at or above this level for 72 h. |
| [storage]
Store at -20°C | [References]
[1] Vernachio JH, et, al. 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
[2] McGuigan C, et, al. 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
[3] Li W, et, al. In Vitro Metabolite Formation in Human Hepatocytes and Cardiomyocytes and Metabolism and Tissue Distribution in Monkeys of the 2'-C-Methylguanosine Prodrug BMS-986094. Int J Toxicol. 2017 Jan 1; 1091581816683642. DOI:10.1177/1091581816683642 |
|
|