Barn, D. R.; Caulfield, W. L.; Cottney, J.; McGurk, K.; Morphy, J. R.; Rankovic, Z.; Roberts, B. published the artcile< Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand>, Computed Properties of 42413-03-6, the main research area is tetrahydroisoquinoline sulfonamide based delta opioid ligand preparation.
A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogs of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimizing a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulfonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physicochem. properties, notably aqueous solubility The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over μ and κ opioid receptors. However the most active and selective compounds had poor aqueous solubility Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test. In the case of compound II, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, III, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, resp., at a dose of 10 mmol/kg i.v.).
Bioorganic & Medicinal Chemistry published new progress about Analgesics. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Computed Properties of 42413-03-6.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics