JPWO2020208002A5

JPWO2020208002A5 -

Info

Publication number: JPWO2020208002A5
Application number: JP2021560094A
Authority: JP
Publication date: 2023-04-12

Claims

Compounds of Formula (I)

(I)
(In the formula,
A is selected from CH or N;
X is selected from CH or N;
R ¹ is selected from the group consisting of H, —CH ₃ and —OCH ₃ ;
^R2 is selected from the group consisting of H and _-CH3 ;
R ³ is selected from the group consisting of H and —CH ₃ , or R ² and R ³ together represent a —(CH ₂ )n-bridge, wherein
n represents a number of 2, 3, 4, or 5, optionally one —CH ₂ — member is replaced by O, S, —NH—, or —N(CH) ₃ —;
Alternatively, the —CH(R ³ )—(R ² )CH— structure in formula (I) consists of furan, thiophene, pyrrole, and N-methyl-pyrrole fused with the piperine ring of formula (I). replaced by a 5-membered heteroaryl group selected from the group
^R4 is selected from the group consisting of H, _-CF3 , and _-OCH3 ;
^R5 is selected from the group consisting of H, -F, and _-OCH3 )
and its salt.

A is selected from CH or N;
X is selected from CH or N;
R ¹ is selected from the group consisting of H, —CH ₃ , —OCH ₃ ;
R ² represents H and R ³ is selected from the group consisting of H and -CH ₃ or R ² represents -CH ₃ and R ³ represents H,
^R4 is selected from the group consisting of H, _-CF3 , and _-OCH3 ;
^R5 is selected from the group consisting of H, -F, and _-OCH3 ;
A compound according to claim 1 and a salt thereof.

A represents N,
R ¹ is selected from the group consisting of H and -CH ₃ ;
^R4 is selected from the group consisting of _-CF3 and _-OCH3 ;
A compound according to claim 1 and a salt thereof.

A represents N,
R ¹ is selected from the group consisting of H and -CH ₃ ;
R ⁴ represents —OCH ₃ ;
A compound according to claim 1 and a salt thereof.

A represents N,
R ¹ is selected from the group consisting of H and -CH ₃ ;
X represents CH,
R ⁴ represents -OCH ₃ ,
R ⁵ represents H,
A compound according to claim 1 and a salt thereof.

A represents N,
R ¹ is selected from the group consisting of H and -CH ₃ ;
X represents N,
R ⁴ represents -OCH ₃ ,
R ⁵ represents H,
A compound according to claim 1 and a salt thereof.

Compounds of formula (Ia), (Ib) or (Ic) according to claims 1, 2, 3, 4, 5 or 6:

and their salts.

2. The compound of claim 1, selected from the group consisting of:

A pharmaceutically acceptable salt of the compound of claim 8.

A pharmaceutical composition comprising any one of the compounds according to claims 1-8 or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

A pharmaceutical composition according to claim 10, comprising one compound according to one or more of claims 1-8 and one or more additional therapeutic agents.

12. A pharmaceutical composition according to claim 10 or 11 for treating diseases or disorders that can be alleviated by TRPC6 inhibition.

12. A pharmaceutical composition according to claim 10 or 11 for use in a method for treating the human or animal body.

12. A pharmaceutical composition according to claim 10 or 11 for use in a method for treating TRPC6-mediated disorders in the human or animal body.

Use of a compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, for the preparation of a pharmaceutical composition for the treatment of diseases or disorders that can be alleviated by TRPC6 modulation .