US 10,479,796 B2 · Spiro-oxazolones

Abstract

The present invention provides spiro-oxazolones, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The present compounds are useful as therapeutics acting peripherally and centrally in the conditions of inappropriate secretion of vasopressin, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, aggressive behavior and phase shift sleep disorders, in particular jetlag.

Claims13

Dependent claims

A compound of formula I,

wherein
X1 is C—R1 or N;
X2 is C—R1 or N;
X3 is C—R1 or N;
X4 is C—R1, N or NO;
whereby only one of X1, X2, X3 and X4 is N;
R1 each separately is selected from the group consisting of hydrogen, halogen, hydroxy, C1-6-alkyl and C1-6-alkoxy;
R2 is selected from the group consisting of H and C1-6-alkyl;
R3 is selected from the group consisting of H and C1-6-alkyl;
or R2 and R3 together are ═O;
Y1 is C—R4 or N;
Y2 is C—R4 or N;
Y3 is C—R4 or N;
Y4 is C—R4 or N;
whereby only one of Y1, Y2, Y3 and Y4 is N;
R4 each separately is selected from the group consisting of hydrogen, halogen, halogen-C1-6-alkyl, hydroxy, C1-6-alkyl, C1-6-alkoxy and Si(C1-6-alkyl)3;
m is 1 or 2;
and
n is 1;
or pharmaceutically acceptable salts thereof.

17 more elements

A compound selected from the group consisting of

(1R)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-2,3-dihydro-4′H-spiro[indene-1,5′[1,3]oxazol]-4′-one,
(1S)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-2,3-dihydro-4′H-spiro[indene-1,5′[1,3]oxazol]-4′-one,
1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(4′-oxo-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-2′-yl)-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(4′-oxo-3,4-dihydro-2H,4′H-spiro[naphthalene-1,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-difluoro-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dihydroxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dimethoxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dimethyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-hydroxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-methoxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-[(2R)-4′-oxo-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-2′-yl]-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-[(2R)-5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-[(2S)-4′-oxo-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-2′-yl]-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-[(2S)-5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-3-(trifluoromethyl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-3,4-dihydro-2H,4′H-spiro[naphthalene-1,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5-(trimethylsilyl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[b ]pyridine-6,5′-[1,3]oxazol]-4′-one,
2′-(2-hydroxy-7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(2-methyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(2-methyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′3,3-dimethyl-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-hydroxy-7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-methyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-methyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(4-methyl-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(5,5-dimethyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(6-methyl-1H,1′H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(6-methyl-1′H,3H-spiro[furo[3,4-c]pyridine-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-5-methoxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-5-hydroxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-4-methoxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-4-hydroxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1-oxido-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-5-one,
2-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-7-one,
2′-spiro[5H-furo[3,4-b]pyridine-7,4′-piperidine]-1′-ylspiro[indane-2,5′-oxazole]-4′-one,
2′-spiro[7H-furo[3,4-b]pyridine-5,4′-piperidine]-1′-ylspiro[indane-2,5′-oxazole]-4′-one,
3-(chloromethyl)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
3-(difluoromethyl)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
3-(fluoromethyl)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
3-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-5-one,
3-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-7-one,
3-methyl-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
4-chloro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one,
4-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
4-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5,6-difluoro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5,6-dihydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5,6-dimethoxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5,6-dimethyl-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5-bromo-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-chloro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-fluoro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5-hydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-methoxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-methyl-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
6-chloro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-chloro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one,
6-hydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-methoxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one,
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[furo[3,4-c]pyridine-1,4′-piperidin]-3-one, and
7-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, or a pharmaceutically acceptable salt thereof.

69 more elements

A compound selected from the group consisting of

(+)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-2,3-dihydro-4′H-spiro[indene-1,5′[1,3]oxazol]-4′-one,
(−)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-2,3-dihydro-4′H-spiro[indene-1,5′[1,3]oxazol]-4′-one,
1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(4′-oxo-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-2′-yl)-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(4′-oxo-3,4-dihydro-2H,4′H-spiro[naphthalene-1,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-difluoro-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dihydroxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dimethoxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dimethyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-hydroxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-methoxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-[4′-oxo-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-2′-yl]-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-3-one enantiomer A,
1′-[4′-oxo-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-2′-yl]-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-3-one enantiomer B,
(−)-1′-[5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
(+)-1′5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-3-(trifluoromethyl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-3,4-dihydro-2H,4′H-spiro[naphthalene-1,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-3,4-dihydro-1H,4′H-spiro[naphthalene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5-(trimethylsilyl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[b]pyridine-6,5′-[1,3]oxazol]-4′-one,
2′-(2-methyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(2-methyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3,3-dimethyl-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-methyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-methyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(4-methyl-1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(5,5-dimethyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(6-methyl-1H, 1′H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(6-methyl-1′H,3H-spiro[furo[3,4-c]pyridine-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-5-methoxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-5-hydroxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-5-one,
2-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-7-one,
2′-(1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
3-(chloromethyl)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
3-(difluoromethyl)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
3-(fluoromethyl)-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
3-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-5-one,
3-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-7-one,
3-methyl-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5,7-dihydro-4′H-spiro[cyclopenta[c]pyridine-6,5′-[1,3]oxazol]-4′-one,
4-chloro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one,
4-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
4-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5,6-difluoro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5,6-dihydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5,6-dimethoxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5,6-dimethyl-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5-bromo-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-chloro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-fluoro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5-hydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-methoxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-methyl-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
6-chloro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-chloro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one,
6-hydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-methoxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one,
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[furo[3,4-c]pyridine-1,4′-piperidin]-3-one, and
7-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, or a pharmaceutically acceptable salt thereof.

64 more elements

A compound selected from the group consisting of

1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-difluoro-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5,6-dihydroxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-(5-hydroxy-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
1′-[(2R)-5-methyl-4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-methyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(3-methyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(5,5-dimethyl-1′H,5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(6-methyl-1H, 1′H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
2′-(7,7-dimethyl-1′H,7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-1′-yl)-5-hydroxy-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
3-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-5H-spiro[furo[3,4-b]pyridine-7,4′-piperidin]-5-one,
3-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-7H-spiro[furo[3,4-b]pyridine-5,4′-piperidin]-7-one,
5,6-difluoro-2′-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-4′-one,
5,6-dihydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-fluoro-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
5-hydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one,
6-hydroxy-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, and
6-methyl-1′-(4′-oxo-1,3-dihydro-4′H-spiro[indene-2,5′-[1,3]oxazol]-2′-yl)-1H-spiro[furo[3,4-c]pyridine-3,4′-piperidin]-1-one, or a pharmaceutically acceptable salt thereof.

17 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/174,674Filed 6 Jun 2016 · continuation

Priority

EP 1319860419 Dec 2013

Published

US 2017/0008901 A112 Jan 2017

Granted

19 Nov 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 491/107
Spiro-condensed systems: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61P 5/12
Of the posterior pituitary hormones, e.g. oxytocin, ADH: for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/02
Drugs for disorders of the nervous system: for peripheral neuropathies

Abstract

Facts

Application

15/174,674Filed 6 Jun 2016 · continuation

Priority

EP 1319860419 Dec 2013

Published

US 2017/0008901 A112 Jan 2017

Granted

19 Nov 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 491/107
Spiro-condensed systems: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61P 5/12
Of the posterior pituitary hormones, e.g. oxytocin, ADH: for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/02
Drugs for disorders of the nervous system: for peripheral neuropathies

Spiro-oxazolones

Life of this patent

Abstract

Claims13

Spiro-oxazolones

Life of this patent

Abstract

Claims13