Phenyl tetrahydroisoquinoline compound substituted with heteroaryl
The present invention provides a compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof which has an excellent NHE3 inhibitory effect: A-Y [1] wherein A represents a structure represented by the following formula [2]: wherein R 11 and R 12 each represent a halogen atom or others as described herein, R 2 represents C 1-6 alkyl or others as described herein, ring E represents triazole, tetrazole, pyrimidine, or others as described herein, R 31 and R 32 each represent a hydrogen atom, C 1-6 alkyl, C 1-6 alkoxy, or others as described herein, and W represents a single bond, the formula —NH—, the formula —O—, or the formula —CONH—, and Y represents a hydrogen atom or a structure selected from
1. A compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof:
A-Y [1]
wherein
A represents a structure represented by the following formula [2]:
wherein
R 11 and R 12 are the same or different and each represents a hydrogen atom or a halogen atom,
R 2 represents a hydrogen atom or C 1-6 alkyl,
ring E represents pyrrole, furan, pyrazole, imidazole, isoxazole, oxazole, isothiazole, triazole, oxadiazole, tetrazole, pyridine, pyridazine, pyrimidine, or pyrazine,
R 31 and R 32 are the same or different and each represents a hydrogen atom, cyano, C 1-6 alkyl, C 1-6 alkoxy, or mono-C 1-6 alkylamino, and
W represents a single bond, the formula —NH—, the formula —O—, or the formula —CONH—, and
Y represents a hydrogen atom or a structure selected from
wherein
Z 1 represents a structure of the following formula group [4′]:
Z 3 represents a structure of the following formula [4-a]:
L 2 , L 2 ′, L 2 ″, and L 2 ′″ are the same or different and each represents a structure of the following formula group [5]:
and
A′, A″, and A′″ each represent the same structure as the structure represented by A.
2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
Y is a hydrogen atom or a structure represented by the following formula:
wherein
Z 1 is a structure of the following formula group [4]:
and
L 2 and L 2 ′ are the same,
and
A′ is the same structure as the structure represented by A.
3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
Y is a structure represented by the following formula:
4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
Z 1 is a structure of the following formula group [6]:
5. The compound according to claim 4 or a pharmaceutically acceptable salt thereof, wherein
the structure represented by formula [2] is a structure of the following formula:
6. The compound according to claim 5 or a pharmaceutically acceptable salt thereof, wherein
is a structure of the following formula group [9]:
7. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive.
8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:
9. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is:
10. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is:
11. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is:
12. A method of inhibiting NHE3 activity in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
13. A method of promoting intestinal water secretion in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
14. A method of treating constipation in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
15. A method of inhibiting sodium absorption in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
16. A method of treating hypertension in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
17. A method of treating nephropathy in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
18. A method of treating body fluid retention in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
19. A method of inhibiting phosphorus absorption in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
20. A method of treating hyperphosphatemia in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
21. A method of treating CKD-MBD in a patient in need thereof comprising administering to said patient a compound according to claim 1 or a pharmaceutically acceptable salt thereof.