Treatment and prevention of neuropathic pain with P2Y14 antagonists

Patent metadata

Field	Value
Publication number	US-11708346-B2
Application number	US-202016936951-A
Country	US
Kind code	B2
Filing date	Jul 23, 2020
Priority date	Jul 23, 2019
Publication date	Jul 25, 2023
Grant date	Jul 25, 2023

Abstract

Disclosed herein are methods for treating neuropathic pain in a subject in need thereof. The methods include: administering to a subject in need thereof a therapeutically effective amount of an antagonist of P2Y14.

First claim

What is claimed is:

1. A method for treating neuropathic pain in a subject in need thereof, the method comprising: administering to the subject in need thereof a therapeutically effective amount of an antagonist of P2Y14 of formula (III)

or a pharmaceutically acceptable salt thereof, wherein ring A is aryl, heteroaryl, or cycloalkyl; R 1 is —CO 2 H, —CO 2 (C 1 -C 8 alkyl), or a bioisostere of carboxylate; each R 3 is independently C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 3 -C 6 cycloalkyl, hydroxy, hydroxyalkyl, C 1 -C 8 alkoxy, C 3 -C 6 cycloalkyloxy, aryloxy, halo, C 1 -C 8 haloalkyl, C 1 -C 8 haloalkoxy, —CN, —NO 2 , —NR 5 R 6 , —C(O)R 4 , —CO 2 R 4 , —C(O)NR 5 R 6 , —NR 5 C(O)R 4 , —(CH 2 ) m aryl, —(CH 2 ) m heteroaryl, or —(CH 2 ) m heterocycloalkyl; R 4 , R 5 , and R 6 are independently H or C 1 -C 8 alkyl; X 1 is selected from the group consisting of —(CH 2 ) o —, —C(O)—, —C(O)NH—, —OC(O)NH—, —OC(O)—, —C(O)O—, —C(S)NH—, and —SO 2 —; X 2 is selected from the group consisting of

wherein R 7 is CH 2 , NH, or O; X 3 is a dendron; X 4 is selected from the group consisting of —(CH 2 )o-, —C(O)—, —C(O)NH—, —OC(O)NH—, —OC(O)—, —C(O)O—, —C(S)NH—, —SO 2 —, —NHC(O)—, and

X 5 is a reactive sulfur-containing moiety; m, n, and q are independently 0 or an integer from 1-5; o is an integer from 1-5; and p is 0 or an integer from 1-36.

2. The method of claim 1 , wherein in formula (III), the dendron is carboxyethylpolyamido (CEPAM) dendron that is optionally functionalized in at least one position to include the moiety

wherein R 8 is CH 2 , NH, or O, and R 9 is —NH 2 or —CO 2 H.

Assignees

• Univ Saint Louis
• The Us Secretary Department Of Health And Human Service

Inventors

• Salvemini Daniela
• Jacobson Kenneth Alan

Classifications

• C07D401/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• A61K31/4192

  1,2,3-Triazoles · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61P25/02 Primary

  for peripheral neuropathies · CPC title

• C07D211/34

  with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title