| Synonyms |
VX-787; VX 787; VX787; JNJ-872; JNJ 872; JNJ872; VRT-0928787; VRT 0928787; VRT0928787;pimodivir; (2S,3S)-3-((5-Fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic Acid |
| IUPAC Name |
(2S,3S)-3-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]bicyclo[2.2.2]octane-2-carboxylic acid |
| Molecular Weight |
399.40 |
| Molecular Formula |
C20H19F2N5O2 |
| Canonical SMILES |
C1CC2CCC1C(C2NC3=NC(=NC=C3F)C4=CNC5=NC=C(C=C45)F)C(=O)O |
| InChI |
InChI=1S/C20H19F2N5O2/c21-11-5-12-13(7-24-17(12)23-6-11)18-25-8-14(22)19(27-18)26-16-10-3-1-9(2-4-10)15(16)20(28)29/h5-10,15-16H,1-4H2,(H,23,24)(H,28,29)(H,25,26,27)/t9?,10?,15-,16-/m0/s1 |
| InChIKey |
JGPXDNKSIXAZEQ-SBBZOCNPSA-N |
| Boiling Point |
574.1±50.0 °C at 760 mmHg |
| Flash Point |
301.0±30.1 °C |
| Purity |
98% |
| Density |
1.5±0.1 g/cm3 |
| Solubility |
In vitro:
10 mM in DMSO |
| Appearance |
Powder |
| Storage |
Store in a cool and dry place and at 0 - 4 °C for short term (days to weeks) or -20 °C for long term (months to years). |
| Animal Admin |
The mice are anesthetized by intraperitoneal injection of ketamine/xylazine (50/5 mg/kg), and the animals are infected intranasally with a 90-μL suspension of influenza virus. The virus challenge is approximately four 50% mouse lethal infectious doses. Treatments are given twice a day (at 12 h intervals) for 10 days starting 2 h before virus challenge. Parameters for assessing the infection are survival, mean day of death, body weight changes, and lung infection parameters (hemorrhage score, weight, and virus titer). Animals are weighed individually every other day through day 21 of the infection. Initially, there are 15 mice per group treated with compound and 25 placebos. Five mice in each group are subsequently sacrificed for determination of lung infection parameters. A larger number of placebos are used than compound-treated mice to achieve greater statistical power, especially if some animals in that group survive the infection. One mouse that dies during the treatment period is presumed to have died from treatment trauma because its death occurs well before other mice die from influenza. |
| Complexity |
620 |
| Exact Mass |
399.15068119 |
| Index Of Refraction |
1.688 |
| In Vitro |
Pimodivir rescues macrophages from virus-mediated death at non-cytotoxic concentrations 24 hpi. The EC50 value for Pimodivir are 8 and 12 nM for A(H1N1) and A(H3N2) strains, respectively, whereas the CC50 values are >1 μM, giving selectivity indexes (SI) > 125 and > 83 for A(H1N1) and A(H3N2) strains, respectively. Pimodivir significantly attenuates the transcription of viral M1 RNA in macrophages, which are infected with A(H1N1) or A(H3N2) strains for 8 h. Pimodivir inhibits the transcription of viral but not cellular genes. Pimodivir allows some activation of IAV-mediated expression of several cellular genes, which are involved in tryptophan and nucleotide metabolism. Pimodivir possesses excellent anti-IAV but not immuno/metabolo-modulating effect. Pimodivir (VX-787) is very potent against influenza A strains, including pandemic 2009 H1N1 and avian H5N1. Pimodivir (VX-787) shows potent activity against all influenza A virus strains tested, with an 50 range of 0.13 to 3.2 nM. Pimodivir-selected PB2 variant viruses maintain susceptibility to neuraminidase inhibitors in vitro. |
| In Vivo |
Pimodivir (2, 6, and 20 mg/kg/day, p.o.) and oseltamivir (20 mg/kg/day) completely prevent death in the H1N1pdm virus infection in mice. Pimodivir (20 mg/kg/day) is more effective than oseltamivir (20 mg/kg/day) in improving body weight and reducing the severity of lung infection. Moreover, Pimodivir (VX-787) shows 100% survival in a +48 h delay to treatment mouse influenza model at 10, 3 and 1 mpk (BID × 10 days) whereas the SOC, oseltamivir, provide no survival benefit in this model at 10 mpk. Pimodivir (VX-787; 1, 3, or 10 mg/kg, bid) provided complete survival, with a dose-dependent reduction in BW loss of the mice. |
| Target |
Influenza Virus |
| Vapor Pressure |
0.0±1.7 mmHg at 25°C |
| XLogP3-AA |
3.8 |
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