Amide derivatives of 1-oxa-4,9-diazaspiro undecane compounds having multimodal activity against pain
2 Assignments
0 Petitions
Accused Products
Abstract
The present invention relates to compounds 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.
wherein
Y is
n is 1 or 2;
q is 1, 2, 3, 4, 5 or 6;
X is a bond, —C(O)O—, —C(O)NR8—, —C(O)—, —O— or —C(R4R4′)—;
R1 is C(O)R5 or S(O)2R5.
5 Citations
27 Claims
-
1. A compound of formula (I),
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
-
2. The compound according to claim 1, wherein
R3 and R3′ - are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and substituted or unsubstituted cycloalkyl, with cycloalkyl, if substituted, being substituted by substituents selected from halogen, —
R9, and —
OR9;and R4 is hydrogen, —
OR8, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, —
C(O)OR9, —
C(O)NR9R9′
, —
NR9C(O)R9′
, or —
NR9R9′
″
;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, or a corresponding solvate thereof.
- are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and substituted or unsubstituted cycloalkyl, with cycloalkyl, if substituted, being substituted by substituents selected from halogen, —
-
3. The compound according to claim 1, wherein
R2 is substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclyl; - with cycloalkyl, aryl, or heterocyclyl, if substituted, being substituted by substituents selected from the group consisting of halogen, —
R9, —
OR9, —
NO2, —
NR9R9′
″
, NR9C(O)R9′
, —
NR9SO2R9′
, —
S(O)2NR9R9′
, —
NR9C(O)NR9′
R9″
, —
SR9, —
S(O)R9, S(O)2R9, —
CN, haloalkyl, haloalkoxy, —
C(O)OR9, —
C(O)NR9R9′
, ═
O, —
OCH2CH2OH, —
NR9S(O)2NR9″
R9″
;R9, R9′
, and R9″
are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;R9′
″
is selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;wherein the aryl is phenyl, naphthyl, or anthracene; 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 C3-8 cycloalkyl; 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, or a corresponding solvate thereof.
- with cycloalkyl, aryl, or heterocyclyl, if substituted, being substituted by substituents selected from the group consisting of halogen, —
-
4. The compound according to claim 3, wherein the C1-6 alkyl is isopropyl;
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
the C2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;
the cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;
the aryl is phenyl; and
the heterocyclyl is pyridine, piperidine, thiazole, or morpholine.
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
-
5. The compound according to claim 1, wherein
R3 and R3′ - are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, with cycloalkyl, heterocyclyl or aryl, if substituted, also in alkylaryl, alkylcycloalkyl or alkylheterocyclyl, being substituted by substituents selected from the group consisting of halogen, —
R9, and —
OR9;R9, and R9′
are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;wherein the aryl is phenyl, naphthyl, or anthracene; 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; the alkyl is C1-6 alkyl; and the cycloalkyl is C3-8 cycloalkyl; 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, or a corresponding solvate thereof.
- are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, with cycloalkyl, heterocyclyl or aryl, if substituted, also in alkylaryl, alkylcycloalkyl or alkylheterocyclyl, being substituted by substituents selected from the group consisting of halogen, —
-
6. The compound according to claim 5, wherein the C1-6 alkyl is methyl or isopropyl;
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
the C2-6 is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;
the cycloalkyl is cyclopropyl;
the aryl is phenyl; and
the heterocyclyl is imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzodioxolane, benzodioxane, carbazole or quinazoline.
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
-
7. The compound according to claim 5, wherein R3 and R3′
- are independently selected from the group consisting of hydrogen and unsubstituted C1-6 alkyl.
-
8. The compound according to claim 1, wherein
X is a bond, — - C(O)O—
, —
C(O)NR8—
, —
C(O)—
, —
O—
or —
C(R4R4′
)—
, whereinR4 is hydrogen, —
OR8, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, —
COOR9, —
CONR9R9′
, —
NR9COR9′
, or —
NR9R9′
″
;R4′
is hydrogen, or substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl or substituted or unsubstituted C2-6 alkynyl;R8 and R8′
are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,R9, R9′
and R9″
are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;R9′
″
is selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;wherein the aryl is phenyl, naphthyl, or anthracene; and 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; 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, or a corresponding solvate thereof.
- C(O)O—
-
9. The compound according to claim 8, wherein the C1-6 alkyl is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
the C2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;
the aryl is phenyl; and
the heterocyclyl is imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzodioxolane, benzodioxane, carbazole or quinazoline.
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
-
10. The compound according to claim 1, wherein
R5 is substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl aryl, substituted or unsubstituted alkyl heterocyclyl, substituted or unsubstituted alkyl cycloalkyl, or — - NR8R8′
, wherein the cycloalkyl, aryl or heterocyclyl groups, if substituted, also in alkyl aryl, alkyl heterocyclyl, alkyl cycloalkyl, are substituted by substituents selected from the group consisting of halogen, —
R9, —
OR9, —
NO2, —
NR9R9′
″
, —
NR9C(O)R9′
, —
NR9S(O)2R9′
, —
S(O)2NR9R9′
, —
NR9C(O)NR9′
R9″
, —
SR9, —
S(O)R9, —
S(O)2R9, —
CN, haloalkyl, haloalkoxy, —
C(O)OR9 and —
C(O)NR9R9′
;R8 and R8′
are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;R9, R9′
and R9″
are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;R9′
″
is selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;wherein the aryl is phenyl, naphthyl, or anthracene; 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 from the group consisting of nitrogen, oxygen and sulfur; the alkyl is C1-6 alkyl; and the cycloalkyl is C3-8 cycloalkyl; 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, or a corresponding solvate thereof.
- NR8R8′
-
11. The compound according to claim 10, wherein the C1-6 alkyl is methyl, ethyl, or isopropyl;
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
the C2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;
the cycloalkyl is cyclopropyl;
the aryl is phenyl; and
the heterocyclyl is pyridine, thiazole, tetrahydropyran or piperidine.
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
-
12. The compound according to claim 1, wherein
R6, R6′ - R7, and R7′
are independently selected from the group consisting of hydrogen, halogen, —
OR9, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, unsubstituted heterocyclyl, unsubstituted aryl and unsubstituted cycloalkyl;R9, R9′
and R9″
are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl;R9′
″
is selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;wherein the aryl is phenyl, naphthyl, or anthracene; 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 C3-8 cycloalkyl; 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, or a corresponding solvate thereof.
- R7, and R7′
-
13. The compound of claim 12, wherein
the C1-6 alkyl is methyl; - the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
the C2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl;
the cycloalkyl is cyclopropyl;
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, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzodioxolane, benzodioxane, carbazole or quinazoline.
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl;
-
14. The compound of claim 12, wherein R6, R6′
- R7, and R7′
are hydrogen.
- R7, and R7′
-
15. The compound according to claim 1, wherein
R10 and R10′ - are independently selected from the group consisting of hydrogen, halogen, —
OR9, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted —
O—
C1-6 alkyl, substituted or unsubstituted —
O—
C2-6 alkenyl or substituted or unsubstituted —
O—
C2-6 alkynyl.
- are independently selected from the group consisting of hydrogen, halogen, —
-
16. The compound according to claim 15, wherein the C1-6 alkyl is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl; and
the C2-6 alkynyl is ethynyl, propynyl, butynyl, pentynyl, or hexynyl.
- the C2-6 alkenyl is ethenyl, propenyl, butenyl, pentenyl, or hexenyl; and
-
17. The compound according to claim 15, wherein R10 and R10′
- are hydrogen.
-
18. The compound according to claim 1, wherein the compound of formula I is a compound of formula I′
-
19. The compound according to claim 1, wherein the compound of formula I is a compound of formula I″
-
20. The compound according to claim 5, wherein the compound of formula I is a compound of formula I′
- ″
- ″
-
21. The compound according to claim 1, which is selected from the group consisting of:
-
(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-2-yl)methanone 1-(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-2-phenylethanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-3-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-4-yl)methanone (4-chloropyridin-2-yl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-methoxyphenyl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-fluorophenyl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone 1-(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone cyclopropyl(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(thiazol-4-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(thiazol-2-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(thiazol-5-yl)methanone 1-(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-2-(pyridin-3-yl)ethanone 1-(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-2-(tetrahydro-2H-pyran-4-yl)ethanone (3-methoxyphenyl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(tetrahydro-2H-pyran-4-yl)methanone 1-(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-2-(pyridin-2-yl)ethanone 2-cyclopropyl-1-(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-(trifluoromethyl)pyridin-2-yl)methanone (5-fluoropyridin-2-yl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanol (5-chloropyridin-2-yl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (3-fluoropyridin-2-yl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (5-fluoropyridin-3-yl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-(trifluoromethyl)pyridin-2-yl)methanone (5-fluoropyridin-2-yl)(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (5-chloropyridin-2-yl)(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone 8-phenethyl-12-[(pyridin-2-yl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 12-[(5-chloropyridin-2-yl)carbonyl]-8-phenethyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane (3-fluoropyridin-2-yl)(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (5-fluoropyrid in-3-yl)(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (5-chloropyridin-3-yl)(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-(trifluoromethyl)pyridin-3-yl)methanone (9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-(2-(6-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[s 0.5]undecan-4-yl)(phenyl)methanone (9-(2-(5-chloropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone 6-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)nicotinonitrile (2-methyl-9-(2-(3-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-(2-(5-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-(2-(4-(trifluoromethyl)pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-(2-(3-nitropyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(6-aminopyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-(2-(2-nitropyridin-3-yl)ethyl)-1-oxa-49-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2,6-difluorophenyl)methanone (9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-2-yl)methanone (9-(2-(3-chloropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-Yl)(2-fluorophenyl)methanone (9-(2-(3-chloropyridin-4-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(3-fluoropyridin-4-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(5-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(2-fluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 1-(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)propan-1-one 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(cyclopropyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(2,6-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 8-(2-(3-chloropyridin-2-yl)ethyl)-12-[(2,6-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane (2-fluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2,6-difluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-(2-hydroxy-2-phenylethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-methoxyphenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone phenyl(9-(2-(pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone 9-phenethyl-N-phenyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide cyclopropyl(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-2-yl)methanone N-methyl-9-phenethyl-N-phenyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(piperidin-1-yl)methanone phenyl(9-(3-(trifluoromethoxy)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone phenyl(9-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone phenyl(9-(2-(pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-methyl-9-(2-(pyridin-3-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(6-methoxypyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-yl)(phenyl)methanone (2-methyl-9-(2-(pyridin-4-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-4-yl)(phenyl)methanone 4-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)benzenesulfonamide (2-methyl-9-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1-oxa-4-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone 4-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)-N-methylbenzenesulfonamide tert-butyl (4-(2-(4-(5-chloropicolinoyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)thiazol-2-yl)carbamate tert-butyl (4-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)thiazol-2-yl)carbamate (2-methyl-9-(3-(trifluoromethoxy)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-2-yl)methanone (2-methyl-9-(2-nitrophenethyl)-1-oxa-49-diazaspiro[5.5]undecan-4-yl)(Phenyl)methanone (2-methyl-9-(3-nitrophenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(Phenyl)methanone 9-phenethyl-4-(phenylsulfonyl)-1-oxa-4,9-diazaspiro[5.5]undecane 4-(isopropylsulfonyl)-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane (2-methyl-9-(3-phenylpropyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-isopentyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (2-methyl-9-(2-(pyridin-2-yl)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-isopropoxyethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone 2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-1-morpholinoethanone 2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-1-(piperidin-1-yl)ethanone 1-(9-(2-fluorophenethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)propan-1-one (9-(2-(5-chloropyridin-3-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(5-fluoropyrid in-3-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone 8-(2-fluorophenethyl)-12-[(pyridin-2-yl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 1-(2-isopropyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone cyclopropyl(2-isopropyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-(3-nitrophenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-benzyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-hydroxyphenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (3-hydroxyphenyl) (9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-hydroxyphenyl)(9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (9-(2-(2-aminothiazol-4-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-chloropyridin-2-yl)methanone (9-(2-(2-aminothiazol-4-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(3-aminophenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-aminophenethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(3-aminophenethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(3-aminopyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone (9-(2-(2-aminopyridin-3-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(phenyl)methanone 1-(3-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)urea 1-(2-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)urea N-(3-(2-(4-benzoyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide N-(2-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide N-(3-(2-(4-benzoyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)acetamide N-(3-(2-(4-benzoyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenyl)methanesulfonamide 2-methyl-9-phenethyl-4-(phenylsulfonyl)-1-oxa-4,9-diazaspiro[5.5]undecane 4-(isopropylsulfonyl)-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan N,N-dimethyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide N,N,2-trimethyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide N-methyl-9-phenethyl-N-(pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide N-cyclopropyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide 9-phenethyl-N-(pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide N-cyclopropyl-N-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide N-methyl-9-phenethyl-N-(pyridin-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide (R)-(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-2-yl)methanone (S)-(2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(pyridin-2-yl)methanone 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(2,3-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(2,4-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 2-(2-(12-(2-fluorobenzoyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-8-yl)ethyl)nicotinonitrile 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(2,5-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 12-[(2-fluorophenyl)carbonyl]-8-(2-(3-methoxypyrid in-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane (2-fluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2,2-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone 12-[(3-fluorophenyl)carbonyl]-8-(2-(3-fluoropyridin-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 12-[(4-fluorophenyl)carbonyl]-8-(2-(3-fluoropyridin-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 8-(2-(3-fluoropyridin-2-yl)ethyl)-12-[(2-methoxyphenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 2-(8-(2-(3-fluoropyridin-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-12-carbonyl)benzonitrile 12-[(2-chlorophenyl)carbonyl]-8-(2-(3-fluoropyridin-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane (2,3-difluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2,2-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone 8-(2-(3-chloropyridin-2-yl)ethyl)-12-[(2,3-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 12-[(2-fluorophenyl)carbonyl]-8-(2-(6-methoxypyridin-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane methyl 3-(12-(2,6-difluorobenzoyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-8-yl)propanoate 12-[(2,6-difluorophenyl)carbonyl]-8-(2-(6-methoxypyridin-2-yl)ethyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane 8-(2,5-difluorophenethyl)-12-[(2,6-difluorophenyl)carbonyl]-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane (R)-(2-fluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (S)-(2-fluorophenyl)(9-(2-(3-fluoropyrid in-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (R)-(2,6-difluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (S)-(2,6-difluorophenyl)(9-(2-(3-fluoropyrid in-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2,3-difluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2,4-difluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2,5-difluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (2-chlorophenyl)(9-(2-(3-fluoropyrid in-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (3-fluorophenyl)(9-(2-(3-fluoropyridin-2-yl)ethyl)-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone, optionally as a stereoisomer, including enantiomers and diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, including enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
-
-
22. A process for the production of a compound of formula I according to claim 1,
-
23. A process for the preparation of a compound of formula I″
- according to claim 19
-
24. A process for the preparation of a compound of formula I′
- ″
according to claim 20
- ″
-
25. 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.
-
26. A method of treating pain in a subject in need thereof, comprising administration of an effective amount of the compound according to claim 1.
-
27. The method according to claim 26, wherein the pain is selected from the group consisting of medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia and hyperalgesia.
-
2. The compound according to claim 1, wherein
Specification
- Resources
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeEsteve Pharmaceuticals S.A. (Corporation Quimico Farmaceutica Esteve SA)
-
Original AssigneeEsteve Pharmaceuticals S.A. (Corporation Quimico Farmaceutica Esteve SA)
-
InventorsVirgili-Bernado, Marina, Alonso-Xalma, Monica, Alegret-Molina, Carlos, Almansa-Rosales, Carmen, Merce-Vidal, Ramon
-
Primary Examiner(s)Anderson, Rebecca L
-
Application NumberUS15/315,095Publication NumberTime in Patent Office1,190 DaysField of SearchUS Class CurrentCPC Class CodesA61P 23/00 AnaestheticsA61P 25/04 Centrally acting analgesics...A61P 25/06 Antimigraine agentsA61P 29/00 Non-central analgesic, anti...C07D 498/10 Spiro-condensed systems