JPWO2019155399A5

JPWO2019155399A5 -

Info

Publication number: JPWO2019155399A5
Application number: JP2020542790A
Authority: JP
Publication date: 2022-02-10
Anticipated expiration: 2039-02-07

Claims

Compound of formula (I):

Or its pharmaceutically acceptable salt; in the formula:
J is a heterocycle with 3-12 ring atoms, where J may be substituted with 1, 2, 3, 4, 5 or 6 R ² ;
K is a C ₆ to C ₁₂ aryl, or K is a heteroaryl having 5 to 12 ring atoms, where K is 1, 2, 3, 4, 5, 6 or 7. ^May be replaced with R3 of;
W is based on the following:

Selected from the group consisting of:
Here, W may be replaced with 1, 2 or ³ R5;
Each R ¹ is independently C ₁ to C ₆ alkyl, C ₃ to C ₆ cycloalkyl, C ₁ to C ₆ alkyl-hydroxy, C ₁ to C ₆ alkoxy, C ₁ to C ₆ alkyl-C ₁ to. Selected from the group consisting of C ₆ alkoxy, hydroxy, C ₂ to C ₆ alkenyl, C ₂ to C ₆ alkynyl, halogen, C ₁ to C ₆ haloalkyl, cyano and -N (R ⁶ ) ₂ , or two. R ¹ may be linked to form a heterocycle having 3 to 12 ring atoms or a C ₃ to C ₆ cycloalkyl;
Each R ² is independently C ₁ to C ₆ alkyl, C ₃ to C ₆ cycloalkyl, hydroxy, C ₁ to C ₆ alkyl-hydroxy, C ₁ to C ₆ alkoxy, halogen, C ₁ to C ₆
Heterocyclic or C ₃ to C ₆ selected from the group consisting of haloalkyl, cyano, C ₁ to C ₆ alkyl-cyano and oxo, or concatenated with ² R 2s and having 3 to 12 ring atoms. Cycloalkyl may be formed;
Each R ³ is independently C ₁ to C ₆ alkyl, C ₃ to C ₆ cycloalkyl, hydroxy, C ₁ to C ₆ alkoxy, C ₁ to C ₆ alkyl-hydroxy, halogen, C ₁ to C ₆ halo. -Heterocycles selected from the group consisting of alkyl, N (R ⁶ ) ₂ , oxo and cyano, or optionally linked with ³ to 12 ring atoms or C ₃ to C. ₆ Cycloalkyl may be formed;
^R4 is -XYZ, where:
X is absent or selected from the group consisting of oxygen, sulfur and -NR ^6-
Y is absent or C ₁ to C ₆ alkylyl, and Z is H, -N (R ⁶ ) ₂ , -C (O) -N (R ⁶ ) ₂ , -OR ⁶ Selected from _3-12 ring atoms heterocycles, 5-12 ring atoms heteroaryls and C3 _– C6 cycloalkyls.
Here, R ⁴ may be replaced by one or more R ^7s ;
Each R ⁵ is independently selected from the group consisting of C ₁ to C ₆ alkyl, hydroxy, C ₁ to C ₆ alkoxy, halogen and -N (R ⁶ ) ₂ .
Each R ⁶ is independently selected from the group consisting of hydrogen, hydroxyl, C ₁ to C ₆ alkoxy and C ₁ to C ₆ alkyl, or two R ^6s are linked to form 3 to 12 Heterocycles with ring atoms or C ₃ to C ₆ cycloalkyls may be formed;
Each R ⁷ is independently R 7'or C ₁ to C ₆ alkyl-R ^7' ^, where each R ^7'is independently C ₁ to C ₆ alkyl, hydroxy, C ₁ -C ₆ Alkoxy, Halogen, -N (R ⁶ ) ₂ , 3 to 12 selected from the group consisting of heterocycles and oxo with ring atoms; and m is 0, 1, 2, 3, 4, 5 , 6 or 7,
The compound or salt.

Compound of formula (I):

Or its pharmaceutically acceptable salt; in the formula:
J is based on the following:

Selected from the group consisting of, where W ^* represents the point of binding to W and J may be substituted with 1, ² , 3, 4, 5 or 6 R2;
K is the following group:

Selected from the group consisting of, or K is the following group:

Selected from the group consisting of, where K may be substituted with 1, 2, ³ , 4, 5, 6 or 7 R3s;
W is based on the following:

Selected from the group consisting of, where W may be substituted with 1, 2 or ³ R5;
Each R ¹ is independently C ₁ to C ₆ alkyl, C ₃ to C ₆ cycloalkyl, C ₁ to C ₆ alkyl-hydroxy, C ₁ to C ₆ alkoxy, C ₁ to C ₆ alkyl-C ₁ to. Selected from the group consisting of C ₆ alkoxy, hydroxy, C ₂ to C ₆ alkenyl, C ₂ to C ₆ alkynyl, halogen, C ₁ to C ₆ haloalkyl, cyano and -N (R ⁶ ) ₂ , or two. R ¹ may be linked to form a heterocycle having 3 to 12 ring atoms or a C ₃ to C ₆ cycloalkyl;
Each R ² is independently C ₁ to C ₆ alkyl, C ₃ to C ₆ cycloalkyl, hydroxy, C ₁ to C ₆ alkyl-hydroxy, C ₁ to C ₆ alkoxy, halogen, C ₁ to C ₆ haloalkyl. , Cocyan, C ₁ to C ₆ selected from the group consisting of alkyl-cyano and oxo, or two R ^2s optionally linked to a heterocycle having 3 to 12 ring atoms or C ₃ to C ₆ Forming cycloalkyl;
Each R ³ is independently C ₁ to C ₆ alkyl, C ₃ to C ₆ cycloalkyl, hydroxy, C ₁ to C ₆ alkoxy, C ₁ to C ₆ alkyl-hydroxy, halogen, C ₁ to C ₆ halo. -Selected from the group consisting of alkyl, N (R ⁶ ) ₂ , oxo and cyano, or a heterocycle in which two R ^3s are linked to have 3 to 12 ring atoms or a C ₃ to C ₆ cyclo. May form alkyl;
^R4 is -XYZ, where:
X is absent or selected from the group consisting of oxygen, sulfur and -NR ^6-
Y is absent or C ₁ to C ₆ alkylyl, and Z is H, -N (R ⁶ ) ₂ , -C (O) -N (R ⁶ ) ₂ , -OR ⁶ Selected from _3-12 ring atoms heterocycles, 5-12 ring atoms heteroaryls and C3 _– C6 cycloalkyls.
Here, R ⁴ may be replaced by one or more R ^7s ;
Each R ⁵ is independently selected from the group consisting of C ₁ to C ₆ alkyl, hydroxy, C ₁ to C ₆ alkoxy, halogen and -N (R ⁶ ) ₂ .
Each R ⁶ is independently selected from the group consisting of hydrogen, hydroxyl, C ₁ to C ₆ alkoxy and C ₁ to C ₆ alkyl, or two R ^6s are linked to form 3 to 12 Heterocycles with ring atoms or C ₃ to C ₆ cycloalkyls may be formed;
Each R ⁷ is independently R 7'or C ₁ to C ₆ alkyl-R ^7' ^, where each R ^7'is independently C ₁ to C ₆ alkyl, hydroxy, C ₁ -C ₆ Alkoxy, Halogen, -N (R ⁶ ) ₂ , 3 to 12 selected from the group consisting of heterocycles and oxo with ring atoms; and m is 0, 1, 2, 3, 4, 5 , 6 or 7, said compound or salt.

Compound of formula (I):

Selected from the group consisting of, where W ^* represents the point of binding to W and J may be substituted with ^R2 ;
K is the following group:

Selected from the group consisting of, or K is the following group:

Selected from the group consisting of, where K may be substituted with one or two ^R3s ;
W is based on the following:

Selected from the group consisting of, where W may be substituted with 1, 2 or ³ R5;
R ¹ is independently selected from the group consisting of C ₁ to C ₆ alkyl and C ₁ to C ₆ alkyl-C ₁ to C ₆ alkoxy;
R ² is C ₁ to C ₆ alkyl;
Each R ³ is independently selected from the group consisting of C ₁ to C ₆ alkyl, hydroxy, halogen, C ₁ to C ₆ halo-alkyl and C ₁ to C ₆ alkyl-hydroxy;
^R4 is -XYZ, where:
X is absent or oxygen
Y is absent or C ₁ to C ₆ alkylenlyl, and Z is from a heterocycle with H, -N (R ⁶ ) ₂ , -OR ⁶ and 3 to 12 ring atoms. Selected,
Here, R ⁴ may be replaced by one or more R ^7s ;
Each R ⁵ is independently selected from the group consisting of C ₁ to C ₆ alkyl, hydroxy, C ₁ to C ₆ alkoxy, halogen and -N (R ⁶ ) ₂ .
Each R ⁶ is independently selected from the group consisting of hydrogen and C ₁ to C ₆ alkyl;
Each R ⁷ is independently R 7'or C ₁ to C ₆ alkyl-R ^7' ^, where each R ^7'is independently C ₁ to C ₆ alkyl and -N (R). ⁶ ) Selected from the group consisting of ₂ ;
m is the compound or salt of 0 or 1.

The compound or salt according to claim 2, wherein K is the following group:

A compound or salt selected from the group consisting of.

The compound or salt according to claim 2, wherein K is the following group:

A compound or salt selected from the group consisting of.

The compound or salt according to claim 2, wherein K is the following group:

A compound or salt that is.

The compound or salt according to any one of claims 1 to 6, wherein W is the following group:

A compound or salt that is.

The compound or salt according to any one of claims 1, 2, 4, 5 or 6, wherein J may be substituted as follows:

A compound or salt that is.

The compound or salt according to any one of claims 1, 2, 4, 5, 6, 7 or 8, wherein J is the following group:

A compound or salt selected from the group consisting of.

The compound or salt according to any one of claims 1 to 9, wherein ^R4 is the following group:

A compound or salt selected from the group consisting of.

A compound selected from the group consisting of or a pharmaceutically acceptable salt thereof.

The compound or pharmaceutically acceptable salt according to any one of claims 1 to 12, wherein one or more hydrogen atoms are replaced with deuterium atoms.

A pharmaceutical composition comprising a therapeutically effective amount of the compound according to any one of claims 1 to 13, a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.