Pyridinecarboxamide derivatives, preparation method thereof and pharmaceutical uses thereof
View Patent ↗Pyridinecarboxamide derivatives, preparation methods, and a pharmaceutical uses thereof are provided. In particular, pyridinecarboxamide derivatives represented by general formula (I), wherein the substituents of the formula (I) are defined in the specification are provided. Also provided are a preparation method for the pyridinecarboxamide derivatives of formula (I), a pharmaceutical composition containing the pyridinecarboxamide derivatives, and uses of the pyridinecarboxamide derivatives as therapeutic agents, especially as inhibitors of the Renal Outer Medullary Potassium channel (ROMK) and in the preparation of medicaments for treating and/or preventing hypertension and heart failure.
1. A compound of formula (II),
or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof,
wherein
R 1 is alkyl, wherein the alkyl is optionally further substituted by one or more groups selected from the group consisting of halogen, hydroxyl, alkoxy, cycloalkyl, aryl, and carboxyl;
R 2 is hydrogen;
R 4 is selected from the group consisting of hydrogen, alkyl, halogen, cyano, nitro, alkoxy, cycloalkyl, and aryl;
and
n is 2.
2. The compound of formula (II) according to claim 1 , wherein R 1 is alkyl, wherein the alkyl is optionally further substituted by one or more groups selected from the group consisting of halogen, hydroxyl and alkoxy.
3. The compound of formula (II) according to claim 1 , wherein R 4 is alkyl.
4. The compound of formula (II) according to claim 1 , which is a compound of formula (III):
or pharmaceutically acceptable salt thereof,
wherein R 1 , R 2 , R 4 and n are as defined in claim 1 .
5. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (II) according to claim 1 , and a pharmaceutically acceptable carrier, diluent or excipient.
7. The compound of formula (II) according to claim 2 , wherein R 1 is selected from the group consisting of methyl, ethyl and propyl.
8. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 5 , and a pharmaceutically acceptable carrier, diluent or excipient.
9. The compound according to claim 5 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
10. The compound according to claim 5 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
11. The compound according to claim 5 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 5 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 9 , and a pharmaceutically acceptable carrier, diluent or excipient.
14. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 10 , and a pharmaceutically acceptable carrier, diluent or excipient.
15. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 11 , and a pharmaceutically acceptable carrier, diluent or excipient.
16. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 12 , and a pharmaceutically acceptable carrier, diluent or excipient.