1. 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid with inbuilt β-N-hydroxy-γ-keto-acid pharmacophore as HCV NS5B polymerase inhibitors
R R Deore, G S Chen, C-S Chen, P-T Chang, M-H Chuang, T-R Chern, H-C Wang, J-W Chern Curr Med Chem. 2012;19(4):613-24. doi: 10.2174/092986712798918833.
The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC₅₀ = 9.5 μM) and based on NTP incorporation by NS5B enzyme (IC₅₀ = 5.9 μM). Compound 11c demonstrated antiviral activity (EC₅₀ = 15.7 μM) and good selectivity in HCV genotype 1b replicon Ava.5 cells. Compound 11c reduced the interaction of NTP to NS5B polymerase. Docking model showed that 11c situated in similar orientation to the bound uridine triphosphate in the active site of NS5B polymerase. As a result, 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid was disclosed as a novel inbuilt β-N-Hydroxy-γ-keto-acid pharmacophore for HCV NS5B polymerase inhibitors.
2. 1-(o-tolylmethyl)naphthalene-2-carboxylic acid
R E Gerkin Acta Crystallogr C. 1998 Dec 15;54 ( Pt 12):1885-7. doi: 10.1107/s0108270198009214.
The title acid, C19H16O2, crystallized in space group P1. In this structure, a hydrogen bond of the 'cyclic dimer' type is formed about a center of symmetry. The O(donor)...O(acceptor) distance is 2.647 (1) A. The carboxylic H and O atoms are ordered. The dihedral angle between the best-fit naphthalene plane and the carboxylic acid group plane is 11.1 (2) degrees.
3. Anthracene-1-carboxylic acid
L J Fitzgerald, R E Gerkin Acta Crystallogr C. 1997 Aug 15;53 ( Pt 8):1080-2. doi: 10.1107/s0108270197004927.
The title compound, C15H10O2, was found to crystallize in the centrosymmetric space group P2(1)/n. The hydrogen bonding is of the cyclic dimer type about a center of symmetry. The carboxyl O atoms are ordered as is the carboxyl H atom. The anthracene core, while less nearly planar, shows good agreement with the anthracene cores of anthracene-9-carboxylic acid and anthracene-1,6-dicarboxylic acid. The carboxyl group plane makes a dihedral angle of 12.4 (2) degrees with the best-fit anthracene core plane.
