HIV-1 inhibitor-8

• CAT Number: I045392
• CAS Number: 2826996-78-3
• Molecular Formula: C25H21N5OS
• Molecular Weight: 439.53
• Purity: ≥95%
• Synonyms: 4-[[4-[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenoxy]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-yl]amino]benzonitrile
• InChI: InChI=1S/C25H21N5OS/c1-16-12-19(4-3-10-26)13-17(2)23(16)31-24-21-15-32-11-9-22(21)29-25(30-24)28-20-7-5-18(14-27)6-8-20/h3-8,12-13H,9,11,15H2,1-2H3,(H,28,29,30)/b4-3+
• InChIKey: GLFXFXOZHKJYEL-ONEGZZNKSA-N
• SMILES: CC1=CC(=CC(=C1OC2=NC(=NC3=C2CSCC3)NC4=CC=C(C=C4)C#N)C)C=CC#N

HIV-1 inhibitor-8 is an orally active, low-toxicity and potent HIV‑1 non-nucleoside reverse transcriptase inhibitor (NNRTI). HIV-1 inhibitor-8 yields exceptionally potent antiviral activities (EC50=4.44~54.5 nM) against various HIV‑1 strains. The IC50 of HIV-1 inhibitor-8 against WT HIV-1 reverse transcriptase is 0.081 μM[1].
HIV-1 inhibitor-8 yields exceptionally potent antiviral activities (EC50=4.44~54.5 nM) against various HIV-1 strains and improves resistance profiles (RF = 0.5~5.6). HIV-1 inhibitor-8 exhibits reduces cytotoxicity (CC50=284 μM) and higher SI values (SI = 5210~63992). HIV-1 inhibitor-8 displays better solubility (sol. =12.8 μg/mL) and no significant inhibition of the main CYP enzymes. HIV-1 inhibitor-8 displays an extremely low hERG inhibition with an IC50 value of 19.84 μM in CHO-hERG cells.
HIV-1 inhibitor-8 (2 mg/kg; i.v.) shows a favorable mean CL, volume of distribution and a long terminal half-life[1].
HIV-1 inhibitor-8 (20 mg/kg; p.o.) absorption reaches maximum at 0.25 hours with a plasma concentration value of 16.6 ng/mL and the mean residence time is 2.90 hours[1].

Reference

[1]. Wang Z, et al. Discovery of Novel Dihydrothiopyrano[4,3-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs with Significantly Reduced hERG Inhibitory Activity and Improved Resistance Profiles [published online ahead of print, 2021 Aug 25]. J Med Chem. 2021;10.1021/acs.jmedchem.1c01015.
 [Content Brief]