# US 12,600,726 B2 · Antagonists of the muscarinic acetylcholine receptor M4

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- Number: US 12,600,726 B2
- Document ID: US12600726B2
- Status: Granted
- Kind: B2
- Application number: 16/629,491
- Filed: 2018-07-12
- Published: 2022-02-17
- Granted: 2026-04-14
- Earliest claimed: 2017-07-12
- Assignees: Vanderbilt University
- Applicants: Vanderbilt University
- Inventors: Craig W. Lindsley; Thomas M. Bridges; P. Jeffrey Conn; Aaron M. Bender; Darren W. Engers
- Web page: https://patentgrep.com/patent/US12600726B2

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D 487/04: Ortho-condensed systems
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 493/08: Bridged systems
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Disclosed herein are cyclopropylpiperidine compounds, which may be useful as antagonists of the muscarinic acetylcholine receptor M4 (niAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

## Claims

### Claim 1

A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
A is a thiazol-2,5-diyl, pyridazin-3,6-diyl, pyrazin-2,5-diyl, pyridin-2,5-diyl, or phthalazin-1,4-diyl, wherein A is optionally substituted with 1-4 substituents independently selected from halo, C1-C4 alkyl, and C1-C4 haloalkyl;
Q is selected from NRa, O, and CRbRc;
R1 is selected from —CH═CH—C1-C4 alkyl, —CH═CH-G, C5-C8cycloalkenyl, a 4- to 8-membered monocyclic heterocyclyl, a 6- to 12-membered aryl, and a 5- to 6-membered monocyclic heteroaryl having 1, 2, or 3 heteroatoms independently selected from N, O, and S; wherein the cycloalkenyl, heterocyclyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, cyano, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and —NHCOR′;
G is a 6- to 12-membered aryl optionally substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, cyano, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and —NHCOR′;
R′, at each occurrence, is independently C1-C4 alkyl:
R2 and R3 are independently selected from hydrogen, C1-C4 alkyl, and halo, or R2 and R3 are taken together to form an oxo group;
R6 is selected from C1-C8 alkyl and —(CRfRg)n—Y1;
Rf is hydrogen:
Rg is selected from hydrogen, C1-C4 alkyl and phenyl:
Y1 is selected from: C3-C10-cycloalkyl; C5-C10-cycloalkenyl; phenyl; a 5- to 6-membered heteroaryl having 1, 2 or 3 heteroatoms independently selected from N, O and S; and a 5- to 8-membered heterocyclyl having 1 or 2 heteroatoms independently selected from N, O and S; wherein the cycloalkyl, cycloalkenyl, phenyl, heteroaryl and heterocyclyl are unsubstituted or substituted with 1 or 2 substituents independently selected from C1-C4 alkyl, halo, and C1-C4 haloalkyl;
each Ra, Rb, and Rc is independently selected from hydrogen and C1-C4 alkyl;
m is 0; and
n is 0 or 1.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
Q is NRa; and
Ra is hydrogen.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from phenyl, naphthyl, benzodioxolyl, pyrazolyl, isoxazolyl, thienyl, pyridinyl, quinolinyl, isoquinolinyl, piperidinyl, pyrrolidinyl, morpholinyl, cyclopentenyl, or —CH═CH-G, wherein the phenyl, naphthyl, benzodioxolyl, pyrazolyl, isoxazolyl, thienyl, pyridinyl, quinolinyl, isoquinolinyl, piperidinyl, pyrrolidinyl, morpholinyl, and cyclopentenyl are unsubstituted or substituted with 1, 2 or 3 substituents independently selected from methyl, fluoro, chloro, trifluoromethyl, trifluoromethoxy, methoxy, and cyano; and
G is phenyl optionally substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, cyano, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and —NHCOR′.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R2 is hydrogen; and
R3 is hydrogen.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R2 and R3 are taken together to form an oxo group.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
Rg is hydrogen; and
Y1 is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl, bicyclo[2.2.1]hept-5-en-2-yl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, 7-oxabicyclo[2.2.1]heptanyl, and pyridyl, each unsubstituted or substituted with 1 or 2 substituents independently selected from C1-C4 alkyl, halo, and C1-C4 haloalkyl.

### Claim 8 (depends on 3)

The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein:
Rg is hydrogen; and
Y1 is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl, bicyclo[2.2.1]hept-5-en-2-yl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, 7-oxabicyclo[2.2.1]heptanyl, and pyridyl, each unsubstituted or substituted with 1 or 2 substituents independently selected from C1-C4 alkyl, halo, and C1-C4 haloalkyl.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof,
wherein
A is selected from

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein A is

### Claim 11 (depends on 1)

The compound of claim 1, wherein the compound is selected from:
6-(2-chloro-5-fluorophenyl)-N-[[6-[[3-(trifluoromethyl)-2-pyridyl]methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(4-fluorophenyl)pyridazin-3-amine;
N-((6-(((1R,2R,4S)-7-oxabicyclo[2.2.1]heptan-2-yl)methyl)-6-azaspiro[2.5]octan-1-yl)methyl)-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyridazin-3-amine;
N-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]-6-(2,3,3-trimethylbutyl)-6-azaspiro[2.5]octane-2-carboxamide;
N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)pyridazin-3-yl)-6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octane-1-carboxamide;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-(1,3-dimethylpyrazol-4-yl)pyridin-2-amine;
6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-N-[6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-yl]-6-azaspiro[2.5]octane-2-carboxamide;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-(2,3,3-trimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-chloro-5-fluoro-phenyl)pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-(2,3,3-trimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-(tetrahydropyran-3-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(1-adamantylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-chloro-5-fluoro-phenyl)pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-(2,2-diphenylethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-N-[6-(2-chloro-5-fluoro-phenyl)pyridazin-3-yl]-6-azaspiro[2.5]octane-2-carboxamide;
N-[6-(2-chloro-5-fluoro-phenyl)pyridazin-3-yl]-6-(2,3,3-trimethylbutyl)-6-azaspiro[2.5]octane-2-carboxamide;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-(1,3-dimethylpyrazol-4-yl)pyrazin-2-amine;
5-(1,3-dimethylpyrazol-4-yl)-N-[[6-(2,3,3-trimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyrazin-2-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-(1,3-dimethylpyrazol-4-yl)pyrazin-2-amine;
6-(2-chloro-4-fluoro-phenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(4-methyl-3-pyridyl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-fluorophenyl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(3-fluorophenyl)pyridazin-3-amine;
6-(2,4-difluorophenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(5-fluoro-2-methyl-phenyl)pyridazin-3-amine;
6-(2,5-difluorophenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(5-fluoro-2-methoxy-phenyl)pyridazin-3-amine;
6-(3,4-difluorophenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(3,5-difluorophenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-phenyl-pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2,4-dimethylpyrazol-3-yl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1,3,5-trimethylpyrazol-4-yl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(3,5-dimethylisoxazol-4-yl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-methylpyrazol-3-yl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]pyridazin-3-amine;
N-[4-[6-[[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]amino]pyridazin-3-yl]phenyl]acetamide:
6-(2-chloro-3-fluoro-phenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(3-methyl-2-thienyl)pyridazin-3-amine;
2-[6-[[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]amino]pyridazin-3-yl]-4-fluoro-benzonitrile:
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(7-isoquinolyl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(6-quinolyl)pyridazin-3-amine;
6-(1,3-benzodioxol-5-yl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-naphthyl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-[2-(trifluoromethoxy)phenyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-[4-(trifluoromethyl)-3-pyridyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-(2-methylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-(2-methylpentyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[(6-ethyl-6-azaspiro[2.5]octan-2-yl)methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[(6-propyl-6-azaspiro[2.5]octan-2-yl)methyl]pyridazin-3-amine;
N-[[6-(cyclopropylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-amine;
N-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-amine;
N-[[6-(1-adamantylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-amine;
N-[(6-benzyl-6-azaspiro[2.5]octan-2-yl)methyl]-6-(1,3-dimethylpyrazol-4-yl)pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-(2,2-diphenylethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-(tetrahydropyran-3-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-[(3-methyl-2-pyridyl)methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(1,3-dimethylpyrazol-4-yl)-N-[[6-[[3-(trifluoromethyl)-2-pyridyl]methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine:
(R)-6-(2-chloro-5-fluoro-phenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine:
(R)-6-(2-chloro-5-fluoro-phenyl)-N-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine:
(S)-6-(2-chloro-5-fluoro-phenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine:
(S)-6-(2-chloro-5-fluoro-phenyl)-N-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-(2-chloro-5-fluoro-phenyl)pyridin-2-amine;
5-(2-chloro-5-fluoro-phenyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridin-2-amine;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-(1,3-dimethylpyrazol-4-yl)pyridin-2-amine;
6-(2,4-dimethylpyrazol-3-yl)-N-[[6-(2-tetrahydrofuran-2-ylethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-phenyl-thiazol-2-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-5-phenyl-thiazol-2-amine;
5-phenyl-N-[[6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]thiazol-2-amine;
6-(2,4-dimethylpyrazol-3-yl)-N-[[6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(3,3-difluoropyrrolidin-1-yl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2,4-dimethylpyrazol-3-yl)-N-methyl-pyridazin-3-amine;
2-[[6-(2-chloro-5-fluoro-phenyl)pyridazin-3-yl]oxymethyl]-6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octane;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(1-piperidyl)pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-morpholino-pyridazin-3-amine;
6-(4,4-difluoro-1-piperidyl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-pyrrolidin-1-yl-pyridazin-3-amine;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-morpholino-pyridazin-3-amine;
N-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-morpholino-pyridazin-3-amine;
N-[[6-(1-adamantylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-morpholino-pyridazin-3-amine;
6-morpholino-N-[[6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-2-[[6-(2-chloro-5-fluoro-phenyl)pyridazin-3-yl]oxymethyl]-6-azaspiro[2.5]octane;
2-[[6-(2-chloro-5-fluoro-phenyl)pyridazin-3-yl]oxymethyl]-6-(cyclohexylmethyl)-6-azaspiro[2.5]octane;
N-[(6-benzyl-6-azaspiro[2.5]octan-2-yl)methyl]-4-(1,3-dimethylpyrazol-4-yl)phthalazin-1-amine;
N-[[6-(1-adamantylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-4-(1,3-dimethylpyrazol-4-yl)phthalazin-1-amine;
6-(cyclopenten-1-yl)-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-[(E)-3,3-dimethylbut-1-enyl]-N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-[(E)-2-(p-tolyl)vinyl]pyridazin-3-amine;
4-(1,3-dimethylpyrazol-4-yl)-N-[[6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]phthalazin-1-amine;
N-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-4-(1,3-dimethylpyrazol-4-yl)phthalazin-1-amine;
N-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methyl]-4-(1,3-dimethylpyrazol-4-yl)phthalazin-1-amine;
N-[[6-(5-bicyclo[2.2.1]hept-2-enylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-4-(1,3-dimethylpyrazol-4-yl)phthalazin-1-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-[(3-fluorophenyl)methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-[(4-fluorophenyl)methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[6-[(2-fluorophenyl)methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[(6-benzyl-6-azaspiro[2.5]octan-2-yl)methyl]-6-(2-chloro-5-fluoro-phenyl)pyridazin-3-amine:
(R)-6-(2-chloro-5-fluoro-phenyl)-N-[[6-(tetrahydropyran-3-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine:
(R)-6-(2-chloro-5-fluoro-phenyl)-N-[[6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-(((1R)-6-(bicyclo[2.2.1]hept-5-en-2-ylmethyl)-6-azaspiro[2.5]octan-1-yl)methyl)-6-(2-chloro-5-fluorophenyl)pyridazin-3-amine:
(R)-6-(2-chloro-5-fluorophenyl)-N-((6-(cycloheptylmethyl)-6-azaspiro[2.5]octan-1-yl)methyl)pyridazin-3-amine;
N-(((1R)-6-((7-oxabicyclo[2.2.1]heptan-2-yl)methyl)-6-azaspiro[2.5]octan-1-yl)methyl)-6-(2-chloro-5-fluorophenyl)pyridazin-3-amine;
N-[4-[6-[[(2R)-6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[[(2R)-6-benzyl-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-chloro-5-fluoro-phenyl)pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[(2R)-6-(2-pyridylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
6-(2-chloro-5-fluoro-phenyl)-N-[[(2R)-6-[(3-methyl-2-pyridyl)methyl]-6-azaspiro[2.5]octan-2-yl]methyl]pyridazin-3-amine;
N-[[(2R)-6-(1-adamantylmethyl)-6-azaspiro[2.5]octan-2-yl]methyl]-6-(2-chloro-5-fluoro-phenyl)pyridazin-3-amine;
N-[4-[6-[[6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methylamino]-4,5-dimethyl-pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]-4,5-dimethyl-pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2R)-6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2R)-6-(cycloheptylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2R)-6-(1-adamantylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2R)-6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide;
N-[4-[6-[[(2R)-6-[(3-methyl-2-pyridyl)methyl]-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2R)-6-[(4-fluorophenyl)methyl]-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2S)-6-(3,3-dimethylbutyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide:
N-[4-[6-[[(2S)-6-(cyclohexylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide; and
N-[4-[6-[[(2S)-6-(tetrahydropyran-4-ylmethyl)-6-azaspiro[2.5]octan-2-yl]methylamino]pyridazin-3-yl]phenyl]acetamide;
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 13 (depends on 1)

A method for antagonizing mAChR M4 in a subject, comprising a step of administering to the subject a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

A method for treating motor symptoms of a neurodegenerative disorder in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the neurodegenerative disorder is selected from Parkinson's disease, drug-induced Parkinsonism, dystonia, Tourette's syndrome, dyskinesias, schizophrenia, cognitive deficits associated with schizophrenia, excessive daytime sleepiness, attention deficit hyperactivity disorder (ADHD), Huntington's disease, chorea, cerebral palsy, and progressive supranuclear palsy.