Substituted benzylspiroindolin-2-one analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M1

摘要

In one aspect, the invention relates to substituted benzylspiroindolin-2-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

主权项

1. A compound having a structure represented by a formula: wherein m is 0 or 1; wherein n is 1, 2, or 3; wherein q is 0, 1, or 2; wherein Q1 is CR1a; Q2 is CR1b; Q3 is CR1c; and Q4 is CR1d;
wherein each of R1a, R1b, R1c and R1d is hydrogen; wherein Q5, when present, is O; wherein Q6 is selected from O or NR3;
wherein R3 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 polyhaloalkyl, C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, C3-C8 cycloalkyl-(C1-C3 alkyl), aryl, heteroaryl, aryl-(C1-C3 alkyl), —(C═O)—C3-C6 alkyl, —(C═O)—C3-C6 cycloalkyl, —(C═O)-aryl, —(SO2)—C1-C3 alky; and wherein R3 is substituted with 0-2 groups independently selected from fluoro and C1-C3 alkyl; wherein each of R4a and R4b is hydrogen; wherein each of R5a and R5b, when present, is hydrogen; wherein each of R6a and R6b is hydrogen; wherein Q7 is CR7a; Q8 is CR7b; Q9 is CR7c; and Q10 is CR7d;
wherein each of R7a, R7b, R7c, and R7d, when present, is independently selected from hydrogen and —F; wherein R8 is a pyrazolyl or indazolyl substituted with 0-2 groups selected from methyl, ethyl, propyl, and isopropyl; or a pharmaceutically acceptable salt thereof.