Selective alpha-7 nicotinic receptor agonists and methods for making and using them

US10308638B2 · kind B2 · utility

Assignee

• The Regents of the University of California · US

Inventors

• Palmer Taylor · Village of La Jolla, US
• Gisela-Andrea Camacho-Hernandez · Village of La Jolla, US
• Karl B. Sharpless · Brookline, US
• M. G. Finn · Atlanta, US
• Valery Fokin · Oceanside, US

Key dates

• Filing date: Mar 24, 2016
• Grant date: Jun 4, 2019
• Expiry date: Mar 24, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D473/34
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided her…