1-Hydroxyacridone

SAR of a series of anti-HSV-1 acridone derivatives, and a rational acridone-based design of a new anti-HSV-1 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine series.[Pubmed:17937990]

Bioorg Med Chem. 2008 Jan 1;16(1):313-21.

Herpes Simplex Virus (HSV) infections are among the most common human diseases. In this work, we assess the structural features and electronic properties of a series of ten 1-Hydroxyacridone derivatives (1a-j) recently described as a new class of non-nucleoside inhibitors of Herpes Simplex Virus-1 (HSV-1). Based on these molecules, we applied rigid analogue and isosteric replacement approaches to design and synthesize nine new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine derivatives (2a-i). The biological and computational results of these new molecules were compared with 1-Hydroxyacridones. An inhibitory profile was observed in 10-Cl substituted 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine derivative (2f), which presents the same substituent at the analogous position of 1-Hydroxyacridone derivative (1b). The structure-activity relationship (SAR) studies pointed out the 10-position next to nitrogen atom as important for the anti-HSV-1 profile in the pyrazolo-naphthyridine derivatives tested, which reinforced the promising profile for further experimental investigation. The most potent acridone and pyrazolo-naphthridine derivatives were also submitted to an in silico ADMET screening in order to determine their overall drug-score, which confirmed their potential antiviral profile.