# US 2014/0194415 A1 · Fatty acid synthase inhibitors

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- Number: US 2014/0194415 A1
- Document ID: US20140194415A1
- Status: Published application
- Kind: A1
- Application number: 14/238,418
- Filed: 2012-08-16
- Published: 2014-07-10
- Earliest claimed: 2011-08-19
- Assignees: Glaxosmithkline Intellectual Property (No.2) Limited
- Inventors: Jonathan Michael Ghergurovich; Michael Lee Moore; Cynthia Ann Parrish; Lance Howard Ridgers; Hongyi Lu
- Web page: https://patentgrep.com/patent/US20140194415A1

## CPC

- A61K 31/5386: spiro-condensed or forming part of bridged ring systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 498/10: Spiro-condensed systems
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

This invention relates to spirocyclic piperidines according to Formula (I) and the use of spirocyclic piperidines for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of spirocyclic piperidines in the treatment of cancer.

## Claims

### Claim 1

A compound according to Formula (I),
wherein
R1 is phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl; wherein said phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl, is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C2-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, C3-C7cycloalkylC1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9;
R5 is selected from the group consisting of hydrogen, C1-C4alkyl, C3-C7cycloalkyl, —C1-C3alkylC3-C7cycloalkyl, phenyl, and —C1-C3alkylphenyl;
R6 is hydrogen, C1-C4alkyl, C3-C7cycloalkyl, or —C1-C3alkylC3-C7cycloalkyl;
or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which is optionally substituted 1 or 2 times independently by oxo or C1-C4alkyl;
R7 is hydrogen or methyl;
R9 is a 5- or 6-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted with 1 or 2 substituents selected from halogen, C1-C4alkyl, CF3, C1-C4alkoxy, and —NR5R6;
each R2 is selected from the group consisting of halogen, C1-C6alkyl, hydroxyl, and C1-C4alkoxy;
R3 is selected from the group consisting of: C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl, wherein said C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl is optionally substituted with from 1 to 4 substituents independently selected from the group consisting of: halogen, C1-C6alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OH, —C(═O)OC1-C4alkyl, —C(═O)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, hydroxyC1-C6alky-, C1-C4alkoxy, C3-C7cycloalkoxy, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NHC(O)C1-C4alkyl, —NHCONR5R6, —NHSO2C1-C4alkyl, and —NHSO2NR5R6;
each R4 and R4a is independently selected from hydrogen, halogen, C1-C6alkyl, hydroxyl, or C1-C6alkoxy;
wherein R8 and R8a are independently selected from hydrogen, deuterium, cyano, optionally substituted C1-C4alkyl, —C1-C4alkylhydroxy, C1-C6alkoxy, —C1-C4alkyl(═O)OH, —C1-C4alkyl(═O)OC1-C4alkyl, —C1-C4alkyl(═O)NR5R6, —C1-C4alkyl(═O)C1-C4alkyl, —C1-C4alkylSO2C1-C4alkyl, —SO2C1-C4alkyl, —C1-C4alkylSO2NR5R6, —SO2NR5R6, —C1-C4alkylNR5R6, —C1-C4alkylNR5SO2C1-C4alkyl, —C1-C4alkylNR5SO2NR5R6, —C1-C4alkylNR5C(═O)C1-C4alkyl, —C1-C4alkylNR5C(═O)NR5R6, C1-C4alkyl(═O)NR5OR6, triazolyl, and R9 wherein any C1-C4alkyl and C1-C6alkoxy moiety is optionally substituted with from 1 to 6 substituents independently selected from the group of: halogen, C1-C4alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)phenyl, —C1-C4alkylC(═O)OH, C(═O)OH, —C(═O)OC1-C4alkyl, —CONR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(O)C1-C4alkyl, —NR7CONR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6, and R9, wherein when R8 is hydrogen R8a is not hydrogen or deuterium and wherein when R8 is deuterium R8a is not hydrogen or deuterium;
or R8 and R8a taken together with the carbon to which they are attached represent a 3- to 6-membered saturated ring optionally containing one or two heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted 1 to 3 times by oxo, C1-C4alkyl, halogen, C1-C4alkylhydroxy, C1-C4alkoxy, or —NR5R6;
m is 0, 1, 2 or 3;
Y is C or N;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A compound of claim 1 according to Formula (I)(A),
wherein
R1 is phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl; wherein said phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl, is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C2-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9;
R5 is selected from the group consisting of hydrogen, C1-C4alkyl, C3-C7cycloalkyl, —C1-C3alkylC3-C7cycloalkyl, phenyl, and —C1-C3alkylphenyl;
R6 is hydrogen, C1-C4alkyl, C3-C7cycloalkyl, or —C1-C3alkylC3-C7cycloalkyl;
or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which is optionally substituted 1 or 2 times independently by oxo or C1-C4alkyl;
R7 is hydrogen or methyl;
R9 is a 5- or 6-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted with 1 or 2 substituents selected from halogen, C1-C4alkyl, CF3, C1-C4alkoxy, and —NR5R6;
each R2 is selected from the group consisting of halogen, C1-C6alkyl, hydroxyl, and C1-C4alkoxy;
R3 is selected from the group consisting of: C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl, wherein said C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl is optionally substituted with from 1 to 4 substituents independently selected from the group consisting of: halogen, C1-C6alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OH, —C(═O)OC1-C4alkyl, —C(═O)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NHC(O)C1-C4alkyl, —NHCONR5R6, —NHSO2C1-C4alkyl, and —NHSO2NR5R6;
each R4 and R4a is independently selected from hydrogen, halogen, C1-C6alkyl, hydroxyl, or C1-C6alkoxy;
wherein R8 and R8a are independently selected from hydrogen, deuterium, cyano, optionally substituted C1-C4alkyl, —C1-C4alkylhydroxy, C1-C6alkoxy, —C1-C4alkyl(═O)OH, —C1-C4alkyl(═O)OC1-C4alkyl, —C1-C4alkyl(═O)NR5R6, —C1-C4alkyl(═O)C1-C4alkyl, —C1-C4alkylSO2C1-C4alkyl, —SO2C1-C4alkyl, —C1-C4alkylSO2NR5R6, —SO2NR5R6, —C1-C4alkylNR5R6, —C1-C4alkylNR5SO2C1-C4alkyl, —C1-C4alkylNR5SO2NR5R6, —C1-C4alkylNR5C(═O)C1-C4alkyl, —C1-C4alkylNR5C(═O)NR5R6, C1-C4alkyl(═O)NR5OR6, triazolyl, and R9 wherein any C1-C4alkyl and C1-C6alkoxy moiety is optionally substituted with from 1 to 6 substituents independently selected from the group of: halogen, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)phenyl, —C1-C4alkyl(═O)OH, —C(═O)OC1-C4alkyl, —CONR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(O)C1-C4alkyl, —NR7CONR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6, triazolyl, and R9, wherein when R8 is hydrogen R8a is not hydrogen or deuterium and wherein when R8 is deuterium R8a is not hydrogen or deuterium;
or R8 and R8a taken together with the carbon to which they are attached represent a 3- to 6-membered saturated ring optionally containing one or two heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted 1 to 3 times by oxo, C1-C4alkyl, halogen, C1-C4alkylhydroxy, C1-C4alkoxy, or —NR5R6;
m is 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

A compound of claim 1 according to Formula (I)(B),
wherein
R1 is phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl; wherein said phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl, is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C2-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, hydroxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9;
R5 is selected from the group consisting of hydrogen, C1-C4alkyl, C3-C7cycloalkyl, —C1-C3alkylC3-C7cycloalkyl, phenyl, and —C1-C3alkylphenyl;
R6 is hydrogen, C1-C4alkyl, C3-C7cycloalkyl, or —C1-C3alkylC3-C7cycloalkyl;
or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which is optionally substituted 1 or 2 times independently by oxo or C1-C4alkyl;
R7 is hydrogen or methyl;
R9 is a 5- or 6-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted with 1 or 2 substituents selected from halogen, C1-C4alkyl, CF3, C1-C4alkoxy, and —NR5R6;
each R2 is selected from the group consisting of halogen, C1-C6alkyl, hydroxyl, and C1-C4alkoxy;
R3 is selected from the group consisting of: C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl, wherein said C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl is optionally substituted with from 1 to 4 substituents independently selected from the group consisting of: halogen, C1-C6alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OH, —C(═O)OC1-C4alkyl, —C(═O)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NHC(O)C1-C4alkyl, —NHCONR5R6, —NHSO2C1-C4alkyl, and —NHSO2NR5R6;
each R4 and R4a is independently selected from hydrogen, halogen, C1-C6alkyl, hydroxyl, or C1-C6alkoxy;
wherein R8 and R8a are independently selected from hydrogen, deuterium, cyano, optionally substituted C1-C4alkyl, —C1-C4alkylhydroxy, C1-C6alkoxy, —C1-C4alkyl(═O)OH, —C1-C4alkyl(═O)OC1-C4alkyl, —C1-C4alkyl(═O)NR5R6, —C1-C4alkyl(═O)C1-C4alkyl, —C1-C4alkylSO2C1-C4alkyl, —SO2C1-C4alkyl, —C1-C4alkylSO2NR5R6, —SO2NR5R6, —C1-C4alkylNR5R6, —C1-C4alkylNR5SO2C1-C4alkyl, —C1-C4alkylNR5SO2NR5R6, —C1-C4alkylNR5C(═O)C1-C4alkyl, —C1-C4alkylNR5C(═O)NR5R6, C1-C4alkyl(═O)NR5OR6, triazolyl, and R9 wherein any C1-C4alkyl and C1-C6alkoxy moiety is optionally substituted with from 1 to 6 substituents independently selected from the group of: halogen, C1-C4alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)phenyl, —C1-C4alkyl(═O)OH, —C(═O)OC1-C4alkyl, —CONR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7 cycloalkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(O)C1-C4alkyl, —NR7CONR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6, triazolyl, and R9, wherein when when R8 is hydrogen R8a is not hydrogen or deuterium and wherein when R8 is deuterium R8a is not hydrogen or deuterium;
or R8 and R8a taken together with the carbon to which they are attached represent a 3- to 6-membered saturated ring optionally containing one or two heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted 1 to 3 times by oxo, C1-C4alkyl, halogen, C1-C4alkylhydroxy, C1-C4alkoxy, or —NR5R6;
m is 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

A compound of claim 1 according to Formula (I)(C),
wherein
R1 is phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl; wherein said phenyl, 5- or 6-membered heteroaryl, naphthyl, 9- or 10-membered heterocyclyl, is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C2-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, hydroxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9;
R5 is selected from the group consisting of hydrogen, C1-C4alkyl, C3-C7cycloalkyl, —C1-C3alkylC3-C7cycloalkyl, phenyl, and —C1-C3alkylphenyl;
R6 is hydrogen, C1-C4alkyl, C3-C7cycloalkyl, or —C1-C3alkylC3-C7cycloalkyl;
or R5 and R6 taken together with the nitrogen to which they are attached represent a 3- to 7-membered saturated ring optionally containing one other heteroatom which is oxygen, nitrogen, or sulfur, which is optionally substituted 1 or 2 times independently by oxo or C1-C4alkyl;
R7 is hydrogen or methyl;
R9 is a 5- or 6-membered heteroaryl ring containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted with 1 or 2 substituents selected from halogen, C1-C4alkyl, CF3, C1-C4alkoxy, and —NR5R6;
each R2 is selected from the group consisting of halogen, C1-C6alkyl, hydroxyl, and C1-C4alkoxy;
R3 is selected from the group consisting of: C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl, wherein said C1-C6alkyl, C3-C7cycloalkyl, hydroxyC1-C6alky-, and C4-C6heterocycloalkyl is optionally substituted with from 1 to 4 substituents independently selected from the group consisting of: halogen, C1-C6alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OH, —C(═O)OC1-C4alkyl, —C(═O)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NHC(O)C1-C4alkyl, —NHCONR5R6, —NHSO2C1-C4alkyl, and —NHSO2NR5R6;
each R4 and R4a is independently selected from hydrogen, halogen, C1-C6alkyl, hydroxyl, or C1-C6alkoxy;
wherein R8 and R8a are independently selected from hydrogen, deuterium, cyano, optionally substituted C1-C4alkyl, —C1-C4alkylhydroxy, C1-C6alkoxy, —C1-C4alkyl(═O)OH, —C1-C4alkyl(═O)OC1-C4alkyl, —C1-C4alkyl(═O)NR5R6, —C1-C4alkyl(═O)C1-C4alkyl, —C1-C4alkylSO2C1-C4alkyl, —SO2C1-C4alkyl, —C1-C4alkylSO2NR5R6, —SO2NR5R6, —C1-C4alkylNR5R6, —C1-C4alkylNR5SO2C1-C4alkyl, —C1-C4alkylNR5SO2NR5R6, —C1-C4alkylNR5C(═O)C1-C4alkyl, —C1-C4alkylNR5C(═O)NR5R6, C1-C4alkyl(═O)NR5OR6, triazolyl, and R9 wherein any C1-C4alkyl and C1-C6alkoxy moiety is optionally substituted with from 1 to 6 substituents independently selected from the group of: halogen, C1-C4alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)phenyl, —C1-C4alkyl(═O)OH, —C(═O)OC1-C4alkyl, —CONR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(O)C1-C4alkyl, —NR7CONR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6, triazolyl, and R9, wherein when R8 is hydrogen R8a is not hydrogen or deuterium and wherein when R8 is deuterium R8a is not hydrogen or deuterium;
or R8 and R8a taken together with the carbon to which they are attached represent a 3- to 6-membered saturated ring optionally containing one or two heteroatoms selected from oxygen, nitrogen, and sulfur, which is optionally substituted 1 to 3 times by oxo, C1-C4alkyl, halogen, C1-C4alkylhydroxy, C1-C4alkoxy, or —NR5R6;
m is 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

A compound of claim 1 according to Formula (I)(D),
wherein
R1 is phenyl, naphthyl, quinolyl, isoquinolyl, wherein said phenyl, naphthyl, quinolyl isoquinolyl, is optionally substituted with from 1 to 3 substituents independently selected from:
optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, -cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, and —OCF3;
each R2 is selected from the group consisting of halogen, C1-C6alkyl, hydroxyl, cyano, and C1-C4alkoxy;
R3 is selected from the group consisting of: C1-C6alkyl and C3-C7cycloalkyl,
wherein R8 and R8a are independently selected from hydrogen, deuterium, cyano, C1-C4alkyl, —C1-C4alkylhydroxy, C1-C6alkoxy, —C1-C4alkyl(═O)OH, —C1-C4alkyl(═O)OC1-C4alkyl, —C1-C4alkyl(═O)NR5R6, —C1-C4alkylNR5R6, —C1-C4alkylNR5C(═O)C1-C4alkyl, —C1-C4alkylNR5C(═O)NR5R6, C1-C4alkyl(═O)NR5OR6, and triazolyl wherein when when R8 is hydrogen R8a is not hydrogen or deuterium and wherein when R8 is deuterium R8a is not hydrogen or deuterium;
R5 is selected from the group consisting of hydrogen and C1-C4alkyl;
R6 is hydrogen and C1-C4alkyl,
m is 0, 1, 2 or 3;
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is phenyl optionally substituted with from 1 to 3 substituents independently selected from: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C1-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, C3-C7cycloalkylC1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9.

### Claim 7 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is selected from furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, or triazinyl, wherein said furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, and triazinyl all of which are optionally substituted with from 1 to 3 substituents independently selected from: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C1-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, C3-C7cycloalkylC1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9.

### Claim 8 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is naphthyl optionally substituted with from 1 to 3 substituents independently selected from: optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C1-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, C3-C7cycloalkylC1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9.

### Claim 9 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is selected from benzofuranyl, isobenzofuryl, 2,3-dihydrobenzofuryl, 1,3-benzodioxolyl, dihydrobenzodioxinyl, benzothienyl, indolizinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1-H-indazolyl, benzimidazolyl, dihydrobenzimidazolyl, benzoxazolyl, dihydrobenzoxazolyl, benzthiazolyl, benzoisothiazolyl, dihydrobenzoisothiazolyl, indazolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, imidazopyridinyl, imidazopyrimidinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, benzoxadiazolyl, benzthiadiazolyl, benzotriazolyl, triazolopyridinyl, purinyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, quinazolinyl, 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl, or pteridinyl, wherein said benzofuranyl, isobenzofuryl, 2,3-dihydrobenzofuryl, 1,3-benzodioxolyl, dihydrobenzodioxinyl, benzothienyl, indolizinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1-H-indazolyl, benzimidazolyl, dihydrobenzimidazolyl, benzoxazolyl, dihydrobenzoxazolyl, benzthiazolyl, benzoisothiazolyl, dihydrobenzoisothiazolyl, indazolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, imidazopyridinyl, imidazopyrimidinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, benzoxadiazolyl, benzthiadiazolyl, benzotriazolyl, triazolopyridinyl, purinyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, quinazolinyl, 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl, and pteridinyl all of which are optionally substituted with from 1 to 3 substituents independently selected from optionally substituted C1-C6alkyl; —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C1-C6alkylC3-C7cycloalkyl, —C(═O)C3-C7cycloalkyl, —C(═O)(phenyl), —C(═O)OC1-C4alkyl, —C(═O)OH, —C(═O)NR5R6, —O(C1-C4alkyl)NR5R6, phenyl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, halogen, C1-C4alkoxy, C3-C7cycloalkylC1-C4alkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NR7C(═O)C1-C4alkyl, —NR7C(═O)NR5R6, —NR7SO2C1-C4alkyl, —NR7SO2NR5R6 and R9.

### Claim 10 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R1 is selected from phenyl and optionally substituted quinolinyl.

### Claim 11 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R2 is absent or is fluoro, hydroxyl, methyl, or methoxy.

### Claim 12 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1, wherein R3 is selected from ethyl, isopropyl, 1-methylcyclopropyl, 1-hydroxymethylcyclopropyl, and cyclopropyl.

### Claim 13 (depends on 1)

A compound or pharmaceutically acceptable salt according claim 1, wherein:
R1 is selected from the group of: phenyl, indolyl, benzofuranyl, indazolyl, benzoimidazolinyl, naphthalyl, quinolyl, and wherein said phenyl, indolyl, benzofuranyl, indazolyl, benzoimidazolinyl, naphthalyl, quinolyl is optionally substituted with from 1 to 3 substituents independently selected from: C1-C4, methyloxy, cyano, NR5R6 and halogen,
each R2 is selected from the group consisting of halogen, C1-C6alkyl, hydroxyl, and C1-C4alkoxy;
R3 is selected from the group consisting of C1-C6alkyl and cyclopropyl; and
each R4 and R4a is independently selected from hydrogen, oxo, halogen or C1-C6alkyl;
each R8 and R8a is independently selected from hydrogen, deuterium, cyano, optionally substituted C1-C4alkyl, —C1-C4hydroxy, C1-C6alkoxy-C1-C4(═O)OH, —C1-C4(═O)OC1-C4, —C1-C4(═O)NR5R6—C1-C4NR5R6, triazolyl, and R9 wherein any optionally substituted C1-C4alkyl and C1-C6alkoxy moiety is optionally substituted with from 1 to 4 substituents independently selected from the group of: halogen, C1-C4alkyl, —CF3, C3-C7cycloalkyl, —C(═O)C1-C4alkyl, —C(═O)C3-C7cycloalkyl, —C(═O)phenyl, carboxyl, —C(═O)OC1-C4alkyl, —CONR5R6, phenyl, 5- or 6-membered heteroaryl, —SO2C1-C4alkyl, —SO2NR5R6, cyano, oxo, hydroxyl, C1-C4alkoxy, C3-C7cycloalkoxy, hydroxyC1-C4alkyl-, C1-C4alkoxyC1-C4alkyl-, —OCF3, —NR5R6, R5R6NC1-C4alkyl-, —NHC(O)C1-C4alkyl, —NR6CONR5R6, —NR6SO2C1-C4alkyl, —NR6SO2NR5R6, and R9, wherein when one R8 is hydrogen or deuterium, the other R8 is not hydrogen or deuterium;
m is 0, 1, 2 or 3;
Y is C or N;
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

A compound or pharmaceutically acceptable salt according to claim 1 selected from:
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetic acid;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N,N-dimethyl-2-(4-(quinolin-7-yl)phenyl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-methyl-2-(4-(quinolin-7-yl)phenyl)acetamide;
methyl 3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3-(4-(quinolin-7-yl)phenyl)propanoate;
3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3-(4-(quinolin-7-yl)phenyl)propanoic acid;
(−)-3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3-(4-(quinolin-7-yl)phenyl)propanamide;
(+)-3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3-(4-(quinolin-7-yl)phenyl)propanamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undec-9-yl)-2-[2-fluoro-4-(7-quinolinyl)phenyl]acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undec-9-yl)-2-[2-fluoro-4-(7-quinolinyl)phenyl]acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide;
4-cyclopropyl-9-(1-(4-(quinolin-7-yl)phenyl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
4-cyclopropyl-9-(1-(3-fluoro-4′-methoxy-[1,1′-biphenyl]-4-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(+)-4-cyclopropyl-9-(1-(2-fluoro-4-(quinolin-7-yl)phenyl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(−)-4-cyclopropyl-9-(1-(2-fluoro-4-(quinolin-7-yl)phenyl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetonitrile;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetic acid;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetamide;
4-cyclopropyl-9-(2-hydroxy-1-(4-(quinolin-7-yl)phenyl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
methyl 3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-3-(2-fluoro-4-(quinolin-7-yl)phenyl)propanoate;
4-cyclopropyl-9-(2-oxo-1-(4-(quinolin-7-yl)phenyl)propyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(+)-4-cyclopropyl-9-(1-(2-fluoro-4-(quinolin-7-yl)phenyl)-2-hydroxyethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(−)-4-cyclopropyl-9-(1-(2-fluoro-4-(quinolin-7-yl)phenyl)-2-hydroxyethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N-methylacetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N-methylacetamide;
(+)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-2-(4-(1-(hydroxymethyl)cyclopropyl)-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(−)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-2-(4-(1-(hydroxymethyl)cyclopropyl)-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-methylquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-methylquinolin-7-yl)phenyl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(3-fluoro-4′-methoxy-[1,1′-biphenyl]-4-yl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-hydroxyquinolin-7-yl)phenyl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(3,4′-difluoro-[1,1′-biphenyl]-4-yl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N-hydroxyacetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N-hydroxyacetamide;
(+)-4-cyclopropyl-9-(1-(2,6-difluoro-4-(quinolin-7-yl)phenyl)-2-hydroxyethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(−)-4-cyclopropyl-9-(1-(2,6-difluoro-4-(quinolin-7-yl)phenyl)-2-hydroxyethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-5-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-5-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N,N-dimethylacetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N,N-dimethylacetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-methylquinolin-5-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-methylquinolin-5-yl)phenyl)acetamide;
(+)-methyl 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methoxyquinolin-7-yl)phenyl)acetate;
(−)-methyl 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methoxyquinolin-7-yl)phenyl)acetate;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-hydroxyquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(2-hydroxyquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N-methoxyacetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-N-methoxyacetamide;
(+)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-fluoroquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-fluoroquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-methoxyquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-methoxyquinolin-7-yl)phenyl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2,6-difluoro-4-(quinolin-7-yl)phenyl)acetamide;
ethyl 2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetate;
(+)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetamide;
(−)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-fluoroquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-fluoroquinolin-7-yl)phenyl)acetamide;
2-(4-(3-cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(4-(3-cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(−)-2-(4-(3-cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(4-(3-chloroquinolin-7-yl)-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(−)-2-(4-(3-chloroquinolin-7-yl)-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-fluoroquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-fluoroquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-fluoroquinolin-7-yl)phenyl)acetamide;
2-(2,6-difluoro-4-(quinolin-7-yl)phenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(2,6-difluoro-4-(quinolin-7-yl)phenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(−)-2-(2,6-difluoro-4-(quinolin-7-yl)phenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2,6-difluoro-4-(quinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2,6-difluoro-4-(quinolin-7-yl)phenyl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methoxyquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methoxyquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-methoxyquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-methoxyquinolin-7-yl)phenyl)acetamide;
4-cyclopropyl-9-((2-fluoro-4-(quinolin-7-yl)phenyl)(4H-1,2,4-triazol-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(+)-4-cyclopropyl-9-((2-fluoro-4-(quinolin-7-yl)phenyl)(4H-1,2,4-triazol-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
(−)-4-cyclopropyl-9-((2-fluoro-4-(quinolin-7-yl)phenyl)(4H-1,2,4-triazol-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;
2-(4-(3-cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(4-(3-cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(−)-2-(4-(3-cyanoquinolin-7-yl)-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methylquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-(3-chloroquinolin-7-yl)-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(−)-2-(4-(3-chloroquinolin-7-yl)-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide;
(+)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-fluoroquinolin-7-yl)phenyl)acetamide;
(−)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-fluoroquinolin-7-yl)phenyl)acetamide;
(+)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methoxyquinolin-7-yl)phenyl)acetamide; and
(−)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-methoxyquinolin-7-yl)phenyl)acetamide.

### Claim 15 (depends on 1)

A compound or pharmaceutically acceptable salt thereof according to claim 1 wherein the compound has an enantiomeric excess of one enantiomer over the other.

### Claim 16 (depends on 1)

A compound or pharmaceutically acceptable salt thereof according to claim 1 wherein the compound is an enantiomerically pure R isomer.

### Claim 17 (depends on 1)

A compound or pharmaceutically acceptable salt thereof according to claim 1 wherein the compound is an enantiomerically pure S isomer.

### Claim 18 (depends on 1)

A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 19 (depends on 1)

A method of treating cancer comprising administering to a human in need thereof an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1.

### Claim 20 (depends on 19)

The method of claim 19 wherein the cancer is selected from the group consisting of: gastric, brain (gliomas), glioblastomas, leukemias, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, breast, inflammatory breast cancer, Wilm's tumor, Ewing's sarcoma, Rhabdomyosarcoma, ependymoma, medulloblastoma, colon, head and neck, kidney, lung, liver, melanoma, renal, ovarian, pancreatic, prostate, sarcoma, osteosarcoma, bladder, stomach, and giant cell tumor of bone and thyroid.

### Claim 21 (depends on 1)

A method of treating cancer in a mammal in need thereof, which comprises: administering to such mammal a therapeutically effective amount of
a) a compound of Formula (I), as described in claim 1 or a pharmaceutically acceptable salt thereof; and
b) at least one anti-neoplastic agent.