For research use only. Not for therapeutic Use.
Reverse transcriptase-IN-1 (Compound 12z), a diarylbenzopyrimidine (DABP) analogue, is a potent, orally active HIV-1 nonnucleoside reverse transcriptase inhibitor. Reverse transcriptase-IN-1 has antiviral activity with EC50 values of 3.4 nM, 4.3 nM and 3.6 nM for HIV-1 IIIB, E138K and K103N mutants, respectively. Reverse transcriptase-IN-1 also has an IC50of 13.7 nM against HIV-1 reverse transcriptase enzyme[1].
The oral bioavailability of Reverse transcriptase-IN-1 (Compound 12z) is significantly improved to 16.5% at a dose of 5 mg/kg in rats. The intrinsic rat microsome clearance of Reverse transcriptase-IN-1 is 33.2 μL/min/mg proteins. The PK study and safety assessment of Reverse transcriptase-IN-1 shows that it is absorbed with mean residence times (MRTs) of 11.8 hours (5 mg/kg, p.o.) and 11.4 hours (1 mg/kg, i.v.) at these two doses. The Cmax of Reverse transcriptase-IN-1 is 39.9 ng/mL at a dose of 5 mg/kg. A single-dose toxicity test of Reverse transcriptase-IN-1 in rats shows no mortality, and there is no abnormal body weight decrease in the animals in the week following an intragastrical dose at 293 mg/kg body weigh. The above results indicate that Reverse transcriptase-IN-1 could be an orally bioavailable candidate for human HIV-1 infection research[1].
Catalog Number | I017735 |
CAS Number | 2380001-43-2 |
Synonyms | 4-[[4-[4-[(E)-2-cyanoethenyl]-2-methyl-6-nitroanilino]quinazolin-2-yl]amino]benzonitrile |
Molecular Formula | C25H17N7O2 |
Purity | ≥95% |
InChI | InChI=1S/C25H17N7O2/c1-16-13-18(5-4-12-26)14-22(32(33)34)23(16)30-24-20-6-2-3-7-21(20)29-25(31-24)28-19-10-8-17(15-27)9-11-19/h2-11,13-14H,1H3,(H2,28,29,30,31)/b5-4+ |
InChIKey | MNZKGXAFXCQSCG-SNAWJCMRSA-N |
SMILES | CC1=CC(=CC(=C1NC2=NC(=NC3=CC=CC=C32)NC4=CC=C(C=C4)C#N)[N+](=O)[O-])C=CC#N |
Reference | [1]. Han S, et al. Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. ACS Infect Dis. 2019 Oct 24. |