JPWO2020089025A5

JPWO2020089025A5 -

Info

Publication number: JPWO2020089025A5
Application number: JP2021523214A
Authority: JP
Publication date: 2022-10-05
Anticipated expiration: 2039-10-24

Claims

A compound of formula (I) or a salt thereof.

I
(In the formula,
Ring A is

is selected from the group consisting of
R ¹ is H, F, Cl, Br, CN, —OH, C _1-4 -alkyl, —O—(C _1-4 -alkyl), —(CH ₂ ) _m —COOH, —(CH ₂ ) _m -C(=O)-O-(C _1-4 -alkyl), -(CH ₂ ) _m -C(=O)-heterocyclyl, -(CH ₂ ) _m -C(=O)-NH ₂ , -(CH ₂ ) _m -C(=O)-NH-(C _1-4 -alkyl), -(CH ₂ ) _m -C(=O)-N(C _1-4 -alkyl) ₂ , -C (=O)-NH-C _3-6 -cycloalkyl, -C(=O)-NH-heterocyclyl, -(CH ₂ ) _m -NH-C(=O)-(C _1-3 -alkyl), -N(C _1-3 -alkyl)-C(=O)-(C _1-4 -alkyl), -N(C _1-3 -alkyl)-C(=O)-NH ₂ , -NH-C (=O)-NH-(C _1-4 -alkyl), heterocyclyl, and phenyl;
wherein each alkyl group or alkyl subgroup may be substituted by one or more F atoms or by one OH or —O—(C _1-3 -alkyl) group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl, morpholinyl, OH group, oxo group, C _1-3 -alkyl group, -C(=O)-CH ₃ and -C(=O)-cyclopropyl group, optionally substituted with one or two groups independently selected from the group;
Here, when n is 2, multiple R ¹ may be the same or different;
n is an integer selected from 1 and 2;
m is an integer selected from 0, 1, and 2;
Wherein in any of the above definitions, unless otherwise specified, any alkyl group or alkyl subgroup may be linear or branched, substituted with one or more F atoms, good)

R ¹ is H, F, —OH, C _1-2 -alkyl, —O-(C _1-2 -alkyl), —(CH ₂ ) _m —COOH, —(CH ₂ ) _m —C(=O )—O—(C _1-2 -alkyl), —(CH ₂ ) _m —C(=O)-heterocyclyl, —(CH ₂ ) _m —C(=O)—NH ₂ , —(CH ₂ ) _m —C(=O)—NH—(C _1-4 -alkyl), —(CH ₂ ) _m —C(=O)—N(C _1-2 -alkyl) ₂ , —C(=O)—NH -cyclopropyl, -C(=O)-NH-heterocyclyl, -(CH ₂ ) _m -NH-C(=O)-(C _1-2 -alkyl) and -heterocyclyl,
wherein each alkyl group or alkyl subgroup may be substituted by one or more F atoms or by one OH or —O—(C _1-2 -alkyl) group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl and morpholinyl, OH, oxo, C _1-2 -alkyl, -C(=O)-CH ₃ and optionally substituted with one or two groups independently selected from the group consisting of -C(=O)-cyclopropyl;
wherein m is 0 or 1;
Here, when n is 2, the plurality of R ¹ may be the same or different,
A compound of formula (I) according to claim 1 or a salt thereof.

R ¹ is H, --OH, --CH ₃ , CF ₃ , --O--CH ₃ , --(CH ₂ ) _m --COOH, --(CH ₂ ) _m --C(=O)--O--(CH ₃ ) , -(CH ₂ ) _m -C(=O)-heterocyclyl, -(CH ₂ ) _m -C(=O)-NH ₂ , -C(=O)-NH-(C _1-4 -alkyl), -C(=O)-N(CH ₃ ) ₂ , -C(=O)-NH-cyclopropyl, -C(=O)-NH-tetrahydropyranyl, -(CH ₂ ) _m -NH-C( =O)-(C _1-2 -alkyl), and 3-methyl-2-oxo-imidazolidin-1-yl, wherein each alkyl group or alkyl subgroup is 1-3 optionally substituted by one F atom, or one OH or -O- _CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl and morpholinyl and is optionally substituted with one OH group;
wherein m is 0 or 1;
wherein when n is 2, the plurality of R ¹ may be the same or different, and the second R ¹ group is selected from the group consisting of CH ₃ and CF ₃ ;
3. A compound of formula (I) or a salt thereof according to claim 2.

Ring A is

and
R ¹ is H, F, -OH, C _1-4 -alkyl, -O-(C _1-3 -alkyl), -C(=O)-NH ₂ , -C(=O)-NH-( C _1-4 -alkyl), -C(=O)-N(C _1-4 -alkyl) ₂ and heterocyclyl,
wherein each alkyl group or alkyl subgroup may be substituted by one or more F atoms or by one OH or —O—(C _1-3 -alkyl) group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl and piperidinyl with one C _1-3 -alkyl, -C(=O)-CH ₃ , or -C(=O)-cyclopropyl group; optionally substituted;
wherein when n is 2, the plurality of R ¹ may be the same or different, and the second R ¹ group is CH ₃ ;
n is an integer selected from 1 and 2;
A compound of formula (I) according to claim 1 or a salt thereof.

Ring A is

and
R ¹ is H, F, -OH, -O-(C _1-2 -alkyl), -C(=O)-heterocyclyl, -(CH ₂ ) _m -C(=O)-NH ₂ , -( CH ₂ ) _m -C(=O)-NH-(C _1-4 -alkyl), -(CH ₂ ) _m -C(=O)-N(C _1-4 -alkyl) ₂ , -(CH ₂ ) _m -NH-C(=O)-(C _1-3 -alkyl) and -N(C _1-3 -alkyl)-C(=O)-(C _1-4 -alkyl), is selected from
wherein each alkyl group or alkyl subgroup may be substituted by one or more F atoms or by one OH or —O—(C _1-3 -alkyl) group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl and morpholinyl and is optionally substituted with one _CH3 group;
n is 1;
m is an integer selected from 0 and 1;
A compound of formula (I) according to claim 1 or a salt thereof.

Ring A is

and
R ¹ is H, —(CH ₂ ) _m —COOH, —(CH ₂ ) _m —C(═O)—O—(C _1-3 -alkyl), —C(═O)-heterocyclyl, —( CH ₂ ) _m -C(=O)-NH ₂ , -(CH ₂ ) _m -C(=O)-NH-(C _1-3 -alkyl), and -(CH ₂ ) _m -C(=O )—N(C _1-3 alkyl) ₂ ,
wherein each alkyl group or alkyl subgroup may be substituted with one or more F atoms or with one OH or -O- _CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, piperidinyl, tetrahydropyranyl and morpholinyl and is optionally substituted with one _CH3 group;
n is 1;
m is an integer selected from 0 and 1;
A compound of formula (I) according to claim 1 or a salt thereof.

Ring A is

and
R ¹ is H, —OH, C _1-2 -alkyl, —O—(C _1-2 -alkyl), —(CH ₂ ) _m —COOH, —(CH ₂ ) _m —C(=O)— O—(C _1-2 -alkyl), —(CH ₂ ) _m —C(=O)-heterocyclyl, —(CH ₂ ) _m —C(=O)—NH ₂ , —(CH ₂ ) _m —C (=O)-NH-(C _1-4 -alkyl), -(CH ₂ ) _m -C(=O)-N(C _1-2 -alkyl) ₂ , -C(=O)-NH-cyclo propyl, -C(=O)-NH-heterocyclyl, -(CH ₂ ) _m -NH-C(=O)-(C _1-2 -alkyl), and heterocyclyl;
wherein each alkyl group or alkyl subgroup may be substituted with one or more F atoms or with one OH or -O- _CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, tetrahydropyranyl and morpholinyl, consisting of OH, oxo, C _1-2 -alkyl and -C(=O)-CH ₃ ; optionally substituted with one or two groups independently selected from the group;
Here, when n is 2, multiple R ¹ may be the same or different;
n is an integer selected from 1 and 2;
m is an integer selected from 0 and 1;
A compound of formula (I) according to claim 1 or a salt thereof.

R ¹ is H, --OH, CH ₃ , --O--CH ₃ , --(CH ₂ ) _m --COOH, --(CH ₂ ) _m --C(=O)--O--CH ₃ , --(CH ₂ ) _m -C(=O)-heterocyclyl, -(CH ₂ ) _m -C(=O)-NH ₂ , -(CH ₂ ) _m -C(=O)-NH-(C _1-3 -alkyl), -(CH ₂ ) _m -C(=O)-N(CH ₃ ) ₂ , -C(=O)-NH-cyclopropyl, -C(=O)-NH-heterocyclyl, -(CH ₂ ) _m - NH-C(=O) _-CH3 and -heterocyclyl,
wherein each alkyl group or alkyl subgroup may be substituted with 1 to 3 F atoms or one OH or -O- _CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, and tetrahydropyranyl and is independently selected from the group consisting of OH, oxo, _CH3 , and -C(=O) _-CH3 ; optionally substituted with one or two groups;
wherein m is 0 or 1;
wherein when n is 2, the plurality of R ¹ may be the same or different, and the second R ¹ group is selected from the group consisting of CH ₃ and CF ₃ ;
A compound of formula (I) or a salt thereof according to claim 7.

2. A compound of formula (I) according to claim 1, or a salt thereof, selected from the group consisting of:

A pharmaceutically acceptable salt of a compound according to any one of claims 1-9.

10. A compound of any one of claims 1 to 9 or a pharmaceutical thereof for use in the treatment of cancer, NASH (non-alcoholic steatohepatitis), pulmonary fibrosis, retinopathy, nephropathy, or stroke A pharmaceutical composition comprising a pharmacologically acceptable salt.

A pharmaceutical composition comprising a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, optionally together with one or more inert carriers and/or diluents.

one or more compounds according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents, and one or more inert carriers and/or a diluent together.