# US 10,308,638 B2 · Selective alpha-7 nicotinic receptor agonists and methods for making and using them

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,308,638 B2
- Document ID: US10308638B2
- Status: Granted
- Kind: B2
- Application number: 15/558,986
- Filed: 2016-03-24
- Published: 2018-08-30
- Granted: 2019-06-04
- Earliest claimed: 2015-03-25
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California; The Scripps Research Institute
- Inventors: Palmer Taylor; Gisela-Andrea Camacho-Hernandez; Karl Barry Sharpless; M. G. Finn; Valery Fokin
- Web page: https://patentgrep.com/patent/US10308638B2

## CPC

- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- A61K 31/4192: 1,2,3-Triazoles
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 31/46: 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61P 9/06: Antiarrhythmics
- A61P 9/12: Antihypertensives
- A61P 25/16: Anti-Parkinson drugs
- C07D 249/06: with aryl radicals directly attached to ring atoms
- C07D 401/14: containing three or more hetero rings
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 451/04: with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D 451/14: containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
- C07D 453/02: containing not further condensed quinuclidine ring systems
- C07D 473/34: attached in position 6, e.g. adenine
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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 herein.

## Claims

### Claim 1

A method for:
(a) treating
a Central Nervous System (CNS) disorder involving an acetylcholine-mediated response;
comprising:
administering to a patient or an individual in need thereof, a compound, a compound having the formula:
or
(b) a stereoisomer or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered enterally.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered orally.

### Claim 4 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered parenterally.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered by inhalation spray.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered nasally.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered topically.

### Claim 8 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered intrathecally.

### Claim 9 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered intracerebrally.

### Claim 10 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered epidurally.

### Claim 11 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered intracranially.

### Claim 12 (depends on 1)

The method of claim 1, wherein the compound or formulation is administered rectally.