Alkyl and aryl derivatives of 1-oxa-4,9-diazaspiro undecane compounds having multimodal activity against pain

• US 10,703,765 B2
• Filed: 06/02/2015
• Issued: 07/07/2020
• Est. Priority Date: 06/02/2014
• Status: Active Grant

• Current Assignee: Esteve Pharmaceuticals S.A. (Corporation Quimico Farmaceutica Esteve SA)
• Original Assignee: Esteve Pharmaceuticals S.A. (Corporation Quimico Farmaceutica Esteve SA)
• Inventors: Virgili-Bernado, Marina, Alonso-Xalma, Monica, Alegret-Molina, Carlos, Almansa-Rosales, Carmen, Garcia Lopez, Monica
• Primary Examiner(s): Katakam, Sudhakar
• Application Number:
  US15/314,595
• Publication Number:
  US 20170101420A1
• Time in Patent Office: 1,862 Days
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 498/10 Spiro-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention relates to compounds of general formula (I) having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to diazaspiro undecane compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Claims

1. A compound of Formula I

2. The compound according to claim 1, wherein R₁ is —

(CH2)_r-W—

R_1′

or R₁ is substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylaryl, or substituted or unsubstituted alkylheterocyclyl.

3. The compound according to claim 1, wherein X is a bond;

—

C(R₄R_4′

)—

;

—

C(O)O—

;

—

C(O)NR₅—

;

—

C(O)—

;

or —

O—

.

4. The compound according to claim 1, wherein

m is 1 and

n is 2.

5. The compound according to claim 1, wherein

R₁ is substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, or —

(CH2)_r-W—

R_1′

, wherein

the aryl is phenyl;

and

the alkyl is C_1-6 alkyl.

6. The compound according to claim 5, wherein R₁ is substituted or unsubstituted phenyl;

substituted or unsubstituted pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyran, pyrazole, or imidazole;

substituted or unsubstituted benzyl;

or substituted or unsubstituted alkylheterocyclyl, wherein the heterocyclyl is pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyrane, pyrazole, or imidazole and the alkyl is methyl.

7. The compound according to claim 1, wherein

R_1′

is H, —

CN, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl or R₅;

wherein

the aryl is phenyl;

the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;

and

the cycloalkyl is C_3-8 cycloalkyl.

8. The compound according to claim 7, wherein R_1′

is substituted or unsubstituted phenyl;

substituted or unsubstituted morpholine or tetrahydropyran;

or substituted or unsubstituted cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

9. The compound according to claim 1, wherein

R₂ is H, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl or substituted or unsubstituted C_2-6 alkynyl;

wherein

the aryl is phenyl;

and

the cycloalkyl is Cm cycloalkyl.

10. The compound according to claim 9, wherein R₂ is substituted or unsubstituted phenyl;

substituted or unsubstituted pyridine, piperidine, thiazole, morpholine, tetrahydropyran, pyrazole, thiophene, indole, benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine, or pyrimidine;

substituted or unsubstituted cyclopropyl;

substituted or unsubstituted methyl or isopropyl;

substituted or unsubstituted ethenyl, propenyl, butenyl, pentenyl, or hexenyl;

or substituted or unsubstituted ethynyl, propynyl, butynyl, pentynyl, or hexynyl.

11. The compound according to claim 1, wherein

R₃ and R_3′

are independently selected from the group consisting of H, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylcycloalkyl, wherein

the alkyl is C_1-6 alkyl;

the cycloalkyl is C_3-8 cycloalkyl; and

the aryl is phenyl.

12. The compound according to claim 11, wherein the C_1-6 alkyl is methyl or ethyl;

the C_2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;

the C_2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;

the cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;

the aryl is phenyl; and

the heterocyclyl is imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, or quinazoline.

13. The compound according to claim 1, wherein

R₄ is H, —

OR₅, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, —

COOR₅, —

CONR₅R_5′

, —

NR₅COR_5′

, —

NR5R5′

″

, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl,

and

R_4′

is H or substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl or substituted or unsubstituted C_2-6 alkynyl), wherein

the cycloalkyl is C_3-8 cycloalkyl; and

the aryl is phenyl.

14. The compound according to claim 13, wherein the C_1-6 alkyl is methyl;

the C_2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;

the C_2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;

the heterocyclyl is tetrahydropyran;

the aryl is phenyl; and

the cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

15. The compound according to claim 1, wherein

R₅, R_5′

and R_5″

are independently H, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl or unsubstituted alkylaryl;

R<sub>5′

″</sub>

is H, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl or -Boc, wherein

the alkyl is C_1-6 alkyl;

and

the aryl is phenyl.

16. The compound according to claim 15, wherein the C_1-6 alkyl is methyl, ethyl, or isopropyl;

the C_2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;

the C_2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl; and

the aryl is phenyl.

17. The compound according to claim 1, wherein

R₈ and R_8′

are independently selected from the group consisting of H, —

OR₅, halogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl or substituted or unsubstituted C_2-6 alkynyl.

18. The compound according to claim 17, wherein R₈ and R_8′

are independently selected from the group consisting of substituted or unsubstituted methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;

substituted or unsubstituted ethenyl, propenyl, butenyl, pentenyl, or hexenyl;

or substituted or unsubstituted ethynyl, propynyl, butynyl, pentynyl, or hexynyl.

19. The compound according to claim 1, which is selected from the group consisting of:

4-(4-methoxyphenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-4-(2-methoxyphenyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-methoxyphenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-4-(3-methoxyphenyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-benzyl-9-phenyl-6-oxa-2,9-diazaspiro[4.5]decan-8-one

4-(3-methoxyphenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(R)-2-methyl-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(S)-2-methyl-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-(methoxymethyl)-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(S)-2-(methoxymethyl)-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(R)-2-(methoxymethyl)-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-ethyl-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

methyl 2-(3-oxo-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-2-yl)acetate

4-(3-methoxyphenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-isopropyl-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2,2-dimethyl-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-(benzyloxymethyl)-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-(1-methyl-1H-pyrazol-3-yl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-(5-nitropyridin-2-yl)ethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-methyl-9-(2-(5-nitropyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-methyl-9-(2-(3-nitropyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(pyrimidin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-(2-nitropyridin-3-yl)ethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(4-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(6-aminopyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(4-aminopyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-methyl-9-(2-(6-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminopyridin-4-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(3-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(4-methoxypyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

6-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)nicotinonitrile

9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(5-chloropyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-isopropyl-9-(2-(2-nitropyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(2-(trifluoromethyl)pyridin-4-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)isonicotinonitrile

9-(2-(6-aminopyridin-2-yl)ethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-(2-nitropyridin-3-yl)ethyl)-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-chloropyridin-2-yl)ethyl)-4-((5-fluoropyridin-2-yl)methyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-fluoropyridin-2-yl)ethyl)-4-((5-fluoropyridin-2-yl)methyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-4-(2-(trifluormethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((5-fluoropyridin-2-yl)methyl)-2-methyl-9-(2-(6-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-chloropyridin-4-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-fluorophenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(4-methoxyphenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(thiophen-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(3-fluorophenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(4-fluorophenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(1H-pyrazol-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-methoxyphenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-((tetrahydro-2H-pyran-4-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(3-phenylpropyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-(4-methylthiazol-5-yl)ethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(1H-indol-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(1H-benzo[d]imidazol-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

methyl 3-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propanoate

2-methyl-9-(2-morpholinoethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(4-nitrophenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(3-nitrophenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-nitrophenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

methyl 4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzoate

2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-phenylacetamide

2-methyl-9-(2-phenoxyethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzo[d]oxazol-2(3H)-one

3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5,5]undecan-9-yl)ethyl)benzonitrile

4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzonitrile

9-(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-morpholino-2-oxoethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecen-3-one

9-(2-methoxyphenethyl)-4-(pyridin-2-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-isopentyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(cyclopropylmethyl)-4-(2-fluorophenyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-(3-methoxyphenethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(pyridin-2-yl)ethyl)-4-(pyridin-2-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-(pyridin-2-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(thiazol-4-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-(2-(6-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-methyl-9-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

N-methyl-3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzenesulfonamide

9-(2-(5-fluoropyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(thiazol-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(pyridin-2-yl)ethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-oxo-2-phenylethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

N-methyl-3-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-phenylpropanamide

2-methyl-9-(2-(pyridin-2-yl)ethyl)-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(6-methoxypyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(3-nitrophenethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((6-aminopyridin-2-yl)methy)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((5-chloropyridin-2-yl)methyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

tert-butyl (4-(2-(3-oxo-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)thiazol-2-yl)carbamate

N-methyl-4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzenesulfonamide

4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzenesulfonamide

2-methyl-9-(2-(3-nitro-1H-pyrazol-1-yl)ethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(6-methoxypyridin-3-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(5-(trifluoromethyl)pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(6-chloropyridin-3-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(5-fluoropyridin-3-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(5-chloropyridin-3-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

tert-butyl (1-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)-1H-pyrazol-5-yl)carbamate

tert-butyl (4-(2-(4-(2-fluorophenyl)-2-isopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)thiazol-2-yl)carbamate

tert-butyl (4-(2-(13-oxo-12-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-8-yl)ethyl)thiazol-2-yl)carbamate

tert-butyl (4-(2-(2-methyl-3-oxo-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)thiazol-2-yl)carbamate

9-(2-isopropoxyethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

6-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)picolinonitrile

2-methyl-9-(2-morpholino-2-oxoethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-isopropoxyethyl)-2-methyl-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-fluorophenethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(S)-9-(2-fluorophenethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride

(R)-9-(2-fluorophenethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride

2-methyl-9-(2-oxo-2-(piperidin-1-yl)ethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-oxo-2-(piperidin-1-yl)ethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-fluorophenethyl)-2-methyl-4-(2-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(3-methoxyphenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-phenyl-9-(2-(pyridin-4-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-(methoxymethyl)-9-(2-(pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-(methoxymethyl)-9-(2-methoxyphenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-fluorophenethyl)-4-(2-fluorophenyl)-2-(methoxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-isopropyl-9-(2-methoxyphenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

tert-butyl (4-(2-(4-(2-fluorophenyl)-2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)thiazol-2-yl)carbamate

ethyl 3-(2-(4-(2-fluorophenyl)-2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzoate

3-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-phenylpropanamide

2-methyl-4-phenyl-9-(2-(pyridin-3-yloxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-(2-(2-oxopyrrolidin-1-yl)ethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(1H-pyrazol-4-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-phenethyl-9-phenyl-6-oxa-2,9-diazaspiro[4.5]decan-8-one

9-(2-hydroxy-2-phenylethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(R)-9-((R)-2-hydroxy-2-phenylethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(R)-9-((S)-2-hydroxy-2-phenylethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(S)-9-((S)-2-hydroxy-2-phenylethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(S)-9-((R)-2-hydroxy-2-phenylethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-benzyl-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-benzyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorobenzyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-fluorobenzyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4,9-diphenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyridin-2-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(4-fluorobenzyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyridin-3-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(thiazol-2-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(thiazol-5-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyridin-4-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-((tetrahydro-2H-pyran-4-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(thiazol-4-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-(pyridin-4-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-methoxybenzyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-(thiazol-4-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((1-benzyl-1H-imidazol-2-yl)methyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-(2-(pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-(2-morpholino-2-oxoethyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-((1-methyl-1H-pyrazol-3-yl)methyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-((1-methyl-1H-imidazol-2-yl)methyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((3-fluoropyridin-2-yl)methyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-((6-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(2-(pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((5-fluoropyridin-2-yl)methyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-phenethyl-4-(2-(pyridin-4-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-nitrobenzyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-hydroxy-2-methylpropyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-4-(4-fluorophenyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(4-fluorophenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-fluorophenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-chlorophenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyrazin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

ethyl 3-(2-methyl-3-oxo-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)benzoate

2-methyl-4-(3-nitrophenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-(1-methyl-1H-indazol-3-yl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-(1-methyl-1H-indazol-6-yl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(benzo[d][1,3]dioxol-5-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(benzo[d]thiazol-6-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(benzo[d]thiazol-2-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(pyridin-4-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-methoxyphenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(6-(trifluoromethyl)pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-fluoropyridin-2-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(thiazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-4-(1-methyl-1H-pyrazol-4-yl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(6-methoxypyridin-2-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(6-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluoropyridin-3-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(2-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(5-fluoropyridin-3-yl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(5-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-methyl-9-phenethyl-4-(3-(trifluoromethyl)pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-fluorophenethyl)-2-methyl-4-(3-(trifluoromethyl)pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

(R)-9-(2-fluorophenethyl)-2-methyl-4-(3-(trifluoromethyl)pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride

(S)-9-(2-fluorophenethyl)-2-methyl-4-(3-(trifluoromethyl)pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride

9-(3-aminophenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-aminophenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(4-aminophenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-aminophenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(5-aminopyridin-2-yl)ethyl)-4-(2-fluorophenyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-aminopyridin-2-yl)ethyl)-4-(2-fluorophenyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-aminobenzyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminopyridin-3-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(3-aminophenethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(5-aminopyridin-2-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(3-amino-1H-pyrazol-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminopyridin-3-yl)ethyl)-4-(2-fluorophenyl)-2-isopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminopyridin-3-yl)ethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

N-(4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide

N-(3-(2-methyl-3-oxo-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)phenyl)acetamide

N-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide

(S)—

N-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide

(R)—

N-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide

N-(2-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide

N-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)isobutyramide

1,1-dimethyl-3-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)urea

N-(3-((3-oxo-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methyl)phenyl)acetamide

N-(2-(2-(4-(2-fluorophenyl)-2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)pyridin-3-yl)acetamide

N-(3-(2-(3-oxo-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide

N-(6-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)pyridin-3-yl)acetamide

N-(2-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)pyridin-4-yl)acetamide

N-(6-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)pyridin-2-yl)acetamide

N-(4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)pyridin-2-yl)acetamide

N-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)methanesulfonamide

N-(2-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)methanesulfonamide

N-(4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)methanesulfonamide

N-(3-((3-oxo-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methyl)phenyl)methanesulfonamide

N-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)propane-2-sulfonamide

1-(3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)urea

1-(6-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)pyridin-2-yl)urea

N-[3-(2-{2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl}ethyl)phenyl]aminosulfonamide

3-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzamide

4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzoic acid

3-(2-methyl-3-oxo-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)benzoic acid

3-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propanoic acid

2-(3-oxo-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-2-yl)acetic acid

N, N-dimethyl-3-(2-methyl-3-oxo-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)benzamide

N, N-dimethyl-2-(3-oxo-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-2-yl)acetamide

N, N-dimethyl-4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzamide

N-methyl-4-(2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzamide

3-(2-(4-(2-fluorophenyl)-2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)-N-methylbenzamide

9-(2-hydroxy-2-phenylethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(6-aminopyridin-3-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-(2-(2-hydroxyethoxy)phenethyl)-2-isopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-(3-(2-hydroxyethoxy)phenethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

2-(hydroxymethyl)-9-phenethyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-((1H-imidazol-2-yl)methyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-4-(2-hydroxyphenyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-hydroxyphenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-benzyl-4-(3-hydroxyphenyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-hydroxyphenyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-hydroxyphenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(4-hydroxyphenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(3-hydroxyphenethyl)-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(4-hydroxyphenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(3-hydroxyphenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-hydroxyphenethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-hydroxyphenyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-(2-hydroxyphenethyl)-2-isopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-(3-hydroxyphenethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-hydroxyphenethyl)-4-(pyridin-2-ylmethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-(hydroxymethyl)-9-(2-hydroxyphenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-(3-hydroxypropyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminothiazol-4-yl)ethyl)-4-(2-fluorophenyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminothiazol-4-yl)ethyl)-4-((5-(trifluoromethyl)pyridin-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(5-amino-1H-pyrazol-1-yl)ethyl)-2-methyl-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminothiazol-4-yl)ethyl)-4-(2-fluorophenyl)-2-isopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

9-(2-(2-aminothiazol-4-yl)ethyl)-2-methyl-4-(4-(trifluoromethyl)pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-9-phenethyl-2-((tetrahydro-2H-pyran-4-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-isopropyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-isopropyl-9-(2-(pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

4-(2-fluorophenyl)-2-(3-methoxypropyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

N-methyl-2-(2-methyl-3-oxo-4-phenyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N-phenylacetamide

(R)-2-benzyl-9-phenyl-6-oxa-2,9-diazaspiro[4.5]decan-8-one

(S)-2-benzyl-9-phenyl-6-oxa-2,9-diazaspiro[4.5]decan-8-one;

optionally as a stereoisomer, including enantiomers and diastereomers, a racemate or in form of a mixture of at least two stereoisomers, including enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.

21. A pharmaceutical composition which comprises the compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

20. A process for the preparation of a compound of formula Ia

22. 3-(2-methyl-3-oxo-9-phenethyl-11-oxa-4,9-diazaspiro[5.5]undecan-4-yl)benzonitrile, optionally as a stereoisomer, including enantiomers and diastereomers, a racemate or in form of a mixture of at least two stereoisomers, including enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.