CGRP receptor antagonists
The disclosures herein relate to novel compounds of formula wherein R 1 , R 2 and R 3 are as defined herein, and their use in treating, preventing, ameliorating, controlling or reducing cerebrovascular or vascular disorders associated with CGRP receptor function.
1. A compound of formula (I)
or a salt thereof or an optical isomer thereof, wherein R 1 is
R 2 is H or forms a spirocyclic heterocyclic ring with R 3 ;
R 3 forms a spirocyclic heterocyclic ring with R 2 or is a heterocyclic ring if R 2 is H.
2. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein R 1 is
3. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein R 2 is H and R 3 is
4. The compound according to claim 3 , or a salt thereof or an optical isomer thereof, wherein R 3 is
5. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein R 2 forms a spirocyclic heterocyclic ring with R 3 to form
6. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[8-(piperidin-4-yl)-2,8-diazaspiro[4.5]dec-2-yl]propan-2-yl}-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2, 8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2, 8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide;
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[8-(piperidin-4-yl)-2,8-diazaspiro[4.5]dec-2-yl]propan-2-yl}-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2, 8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-2′-oxo-1′,2′-dihydro-1H-spiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2,8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamide; and
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[8-(pyridin-4-yl)-2,8-diazaspiro[4.5]dec-2-yl]propan-2-yl}-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide;
or a salt thereof or an optical isomer thereof.
7. The compound according to claim 1 , wherein the compound is,
or a salt thereof or an optical isomer thereof.
8. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[8-(piperidin-4-yl)-2,8-diazaspiro[4.5]dec-2-yl]propan-2-yl}-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2, 8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2, 8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide;
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[8-(piperidin-4-yl)-2, 8-diazaspiro[4.5]dec-2-yl]propan-2-yl}-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2, 8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-2′-oxo-1′,2′-dihydro-1H-spiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxamide;
N-[(2R)-1-[8-(N-methyl-D-alanyl)-2,8-diazaspiro[4.5]dec-2-yl]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamide; and
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[8-(pyridin-4-yl)-2, 8-diazaspiro[4.5]dec-2-yl]propan-2-yl}-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide.
9. The compound according to claim 1 , wherein the compound is,