CGRP receptor antagonists
The disclosures herein relate to novel compounds of formula wherein Ar 1 and R 1 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 H or F and Ar 1 is an optionally substituted 5 membered heterocyclic ring containing at least two nitrogen atoms.
2. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein Ar 1 is an optionally substituted five-membered heterocyclic ring including at least two nitrogen atoms, wherein the optional substituents are selected from (C 1 -C 6 )alkyl, CO 2 R 2 where R 2 is H or (C 1 -C 3 )alkyl.
3. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein R 1 is H.
4. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein Ar 1 is a five-membered heterocyclic ring including two or three nitrogen atoms, optionally substituted with (C 1 -C 6 )alkyl.
5. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein Ar 1 is
or
6. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein Ar 1 is
7. The compound according to claim 1 , or a salt thereof or an optical isomer thereof, wherein Ar 1 is
8. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
N-[(2R)-1-[4-(1H-imidazol-2-yl)-1,4′-bipiperidin-1′-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-[4-(4-methyl-1H-imidazol-5-yl)-1,4′-bipiperidin-1′-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)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[4-(1-propyl-1H-imidazol-2-yl)-1,4′-bipiperidin-1′-yl]propan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide;
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-[4-(4-methyl-4H-1,2,4-triazol-3-yl)-1,4′-bipiperidin-1′-yl]-1-oxopropan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide;
4-(7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)-N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-[4-(4-methyl-4H-1,2,4-triazol-3-yl)-1,4′-bipiperidin-1′-yl]-1-oxopropan-2-yl}piperidine-1-carboxamide;
ethyl 5-{1′-[(2R)-3-(7-methyl-1H-indazol-5-yl)-2-({[4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidin-1-yl]carbonyl}amino)propanoyl]-1,4′-bipiperidin-4-yl}-4H-1,2,4-triazole-3-carboxylate;
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[4-(4H-1,2,4-triazol-3-yl)-1,4′-bipiperidin-1′-yl]propan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide;
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-[4-(5-methyl-4H-1,2,4-triazol-3-yl)-1,4′-bipiperidin-1′-yl]-1-oxopropan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide; and
5-{1′-[(2R)-3-(7-methyl-1H-indazol-5-yl)-2-({[4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidin-1-yl]carbonyl}amino)propanoyl]-1,4′-bipiperidin-4-yl}-4H-1,2,4-triazole-3-carboxylic acid;
or a salt thereof or an optical isomer thereof.
9. The compound according to claim 1 , wherein the compound is:
or a salt thereof or an optical isomer thereof.
10. The compound according to claim 1 , wherein the compound is
or a salt thereof or an optical isomer thereof.
11. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
N-[(2R)-1-[4-(1H-imidazol-2-yl)-1,4′-bipiperidin-1′-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-[4-(4-methyl-1H-imidazol-5-yl) -1,4′-bipiperidin-1′-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)-3(7-methyl-1H-indazol-5yl)-1-oxo-1-[4-(1-propyl-1H-imidazol-2-yl) -1,4′-bipiperidin-1′-yl]propan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide;
N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-[4-(4-methyl-4H-1,2,4-triazol-3-yl) -1,4′-bipiperidin-1′-yl]-1-oxopropan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide;
4-(7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)-N-{(2R)-3-(7-methyl-1H-indazol-5-yl) -1-[4-(4-methyl-4H-1,2,4-triazol-3-yl)-1,4′-bipiperidin-1′-yl]-1-oxopropan-2-yl}piperidine-1-carboxamide;
ethyl 5-{1′-[(2R)-3-(7-methyl-1H-indazol-5-yl)-2-({[4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidin-1-yl]carbonyl}amino)propanoyl]-1,4′-bipiperidin-4-yl}-4H-1,2,4-triazole-3-carboxylate;
N-{(2R)-3-(7-methyl-1H-indazol-5yl)-1-oxo-1-[4-(4H-1,2,4-triazol-3-yl) -1,4′-bipiperidin-1′-yl]propan-2-yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide; N-{(2R)-3-(7-methyl-1H-indazol-5-yl)-1-[4-(5-methyl-4H-1,2,4-triazol-3yl) -1,4′-bipiperidin-1′-yl]-1-oxopropan-2yl}-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide; and
5-{1′-[(2R)-3-(7-methyl-1H-indazol-5-yl)-2-({[4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidin-1-yl]carbonyl}amino)propanoyl]-1,4′-bipiperidin-4-yl}-4H-1,2,4-triazole-3-carboxylic acid.
12. The compound of claim 1 , wherein the compound is
13. The compound of claim 1 , wherein the compound is: