US 12,291,521 B2
Indazole compounds as mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
P. Jeffrey Conn, Nashville, TN (US); Craig W. Lindsley, Nashville, TN (US); Andrew S. Felts, Nashville, TN (US); Colleen M. Niswender, Nashville, TN (US); Rory A. Capstick, Nashville, TN (US); Paul K. Spearing, Nashville, TN (US); and Sean R. Bollinger, Nashville, TN (US)
Assigned to Vanderbilt University, Nashville, TN (US)
Filed by Vanderbilt University, Nashville, TN (US)
Filed on Apr. 26, 2022, as Appl. No. 17/730,112.
Application 17/730,112 is a division of application No. 16/639,539, granted, now 11,427,573, previously published as PCT/US2018/046801, filed on Aug. 16, 2018.
Claims priority of provisional application 62/546,290, filed on Aug. 16, 2017.
Prior Publication US 2022/0259190 A1, Aug. 18, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 405/14 (2006.01); A61P 25/00 (2006.01); C07D 401/12 (2006.01); C07D 407/14 (2006.01); C07D 409/14 (2006.01); C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 405/14 (2013.01) [A61P 25/00 (2018.01); C07D 401/12 (2013.01); C07D 407/14 (2013.01); C07D 409/14 (2013.01); C07D 471/04 (2013.01); C07D 519/00 (2013.01)] 20 Claims
 
1. A method for ameliorating a neurotransmission dysfunction associated with mGluR4 activity in a mammal comprising the step of administering to the mammal at least one compound in a dosage and amount effective to treat the dysfunction in the mammal, the compound having a structure represented by a compound of the following formula:

OG Complex Work Unit Chemistry
wherein:
A is chosen from

OG Complex Work Unit Chemistry
X1A: CH, CR1, or N;
X1B: CH, CR1, or N;
X1C: CH, CR1, or N;
X2A: CH, CR1, N, NH2;
X2B: CH, CR1, N, NH2;
X2C: CH, CR1, N, NH2;
X2D: CH, CR1;
each R1 is independent and chosen from H, D, OH, NH2, NR3R4, OR5, F, CHF2, CF3, halogen, F, alkyl, Me, CD3, cycloalkyl, CN, methoxy, alkoxy, alkyl-methoxy, or alkyl-alkoxy;
R2 is chosen from H, D, OH, CONH2, NH2, NR3R4, OR5, F, CHF2, CF3, halogen, F, alkyl, Me, O-Me, alkyl-O-Me, CD3, cycloalkyl, CN, methoxy, alkoxy, alkyl-methoxy, or alkyl-alkoxy;
R3 is chosen from H, alkyl, alkoxy, or OH;
R4 is chosen from H, alkyl, alkoxy, or OH;
R5 is chosen from H, or alkyl;
R6 is H, CH3 or CD3;
R7 is O or —CO—;
R8 is a bond, alkyl, —NH—, —O—, alkyl-O—;
R9 is substituted or unsubstituted and chosen from H, heteroaryl, aryl, heterocycloalkyl, oxygen-containing heterocycle, cycloalkyl, CD3, CF2, CD2-CH3, alkyl, CH3,
n is 0-6;
wherein each heteroaryl, aryl, heterocycloalkyl, cycloalkyl, when chosen, can be optionally substituted with one or more of the following: H, D, OH, CONH2, NH2, NR3R4, OR5, F, CHF2, CF3, halogen, F, alkyl, Me, O-Me, alkyl-O-Me, CD3, CN, methoxy, alkoxy, alkyl-methoxy, or alkyl-alkoxy;
or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable derivative thereof.