Extensive 1D, 2D NMR spectra of some [7.0]metacyclophanes and X-ray analysis of (±)-myricanol

From the hexane extract of the bark of Myrica cerifera, the pentacyclic triterpenes taraxerol and myricadiol were isolated. The EtOH extract afforded the [7.0]metacyclophanes, (±)-myricanol (4), and myricanone (7). Accurate 1H- and 13C-NMR spectral assignments have been made for (±)-myricanol (4), 5,11,17-tri-O-acetyl-(±)-myricanol (5), 11-O-methyl-(±)-myricanol (6), and myricanone (7) by a study of the 1H-1H-COSY, 1H-13C-COSY (HETCOR), selective INEPT, and 1D NOE experiments. The structure of (±)-myricanol was established by a single crystal X-ray analysis. Molecular mechanics MM-3(94) calculations have been made for (R,Sa)- and (S,Sa)-myricanol, and the bond lengths, bond angles, and the torsion angles have been calculated for the energy-minimized conformation

Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis

Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A <i>K</i>_i of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound <b>15h</b>, with PDE10A <i>K</i>_i of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing

Molecular Shape and Medicinal Chemistry: A Perspective

Molecular Shape and Medicinal Chemistry: A Perspectiv