| Identification | Back Directory | [Name]
Benzonitrile, 4-[[4-[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenoxy]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]amino]-2-fluoro- | [CAS]
2834087-69-1 | [Synonyms]
HIV-1 inhibitor-50
Benzonitrile, 4-[[4-[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenoxy]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]amino]-2-fluoro- | [Molecular Formula]
C24H18FN5O2 | [MOL File]
2834087-69-1.mol | [Molecular Weight]
427.43 |
| Hazard Information | Back Directory | [Uses]
HIV-1 invistor-50 is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that targets HIV-1 reverse transcriptase (RT) (IC50=50 nM). HIV-1 inhibitor-50 shows significant antiviral activity, with EC50s of 2.22-53.3nM against HIV-1 IIIB and its mutant strains[1]. | [in vivo]
HIV-1 inhibitor-50 (compound 36a) (hydrochloride; 2 mg/kg; i.v.; single dose) has a high clearance (CL=103 L/h/kg) and a modest half-life (T1/2=1.43 h)[1].
HIV-1 inhibitor-50 (hydrochloride; 2000 mg/kg; p.o.; single dose) doesn’t result any abnormal behaviors or significant changes in body weight compared with the control in 7 days, indicating no acute toxicity[1].
Pharmacokinetic Analysis[1]
| Route | Dose (mg/kg) | T1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUC0-t (h·ng/mL) | AUC0-∞ (h·ng/mL) | CL (L/h/kg) | F (%) | | i.v. | 2 | 1.43 | 0 | 484 | 250 | 255 | 103 | / | | p.o. | 10 | 5.12 | 0.25 | 37.5 | 107 | 154 | / | 12.1 |
| [IC 50]
HIV-1 (WT): 3.04 nM (EC50); HIV-1 (L100I): 3.04 nM (EC50); HIV-1 (K103N): 2.87 nM (EC50); HIV-1 (Y181C): 10.2 nM (EC50); HIV-1 (Y188L): 13.2 nM (EC50); HIV-1 (E138K): 9.77 nM (EC50); HIV-1 (F227L+V106A): 19.8 nM (EC50) | [References]
[1] Sun Y, et al. Lead Optimization and Avoidance of Metabolic-perturbing Motif Developing Novel Diarylpyrimidines as Potent HIV-1 NNRTIs. J Med Chem. 2022 Dec 8;65(23):15608-15626. DOI:10.1021/acs.jmedchem.2c00576 |
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