Pyridinyl sulfonamide derivatives, pharmaceutical compositions and uses thereof

Patent metadata

Field	Value
Publication number	US-12178809-B2
Application number	US-201917285918-A
Country	US
Kind code	B2
Filing date	Oct 24, 2019
Priority date	Oct 29, 2018
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

The invention relates to new pyridinyl sulfonamide derivatives of the formula

wherein R 1 , A and n are as defined herein, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein
ring A is selected from the group consisting of:

R 1 is selected from the group consisting of H, F, Cl, Br, CN, —OH, C 1-4 -alkyl, alkyl), —(CH 2 ) m —COOH, —(CH 2 ) m —C(═O)—O—(C 1-4 -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 , —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 sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C 1-3 -alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinylpiperidinyl, tetrahydropyranyl and morpholinyl, and each heterocycl is optionally substituted with one or two groups independently selected from the group consisting of oxo, C 1-3 -alkyl, —C(═O)—CH 3 and —C(═O)-cyclopropyl; and
wherein multiple R 1 may be identical or different, if n is 2; and

n is an integer selected from 1 and 2; and
m is an integer selected from 0, 1 and 2; and
wherein in any definition mentioned hereinbefore, if not specified otherwise, any alkyl group or sub-group may be straight-chained or branched and is optionally substituted with 1 or more F atoms,
or a salt thereof.

2. The compound of formula (I) according to claim 1 , wherein
R 1 is selected from the group consisting of:
H, F, Cl, —OH, —O—(C 1-2 -alkyl), —(CH 2 ) m —COOH, —(CH 2 ) m —C(═O)—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(CH 3 )(C 1-3 -alkyl), —C(═O)—NH-cyclopropyl, —C(═O)—NH-heterocyclyl, —(CH 2 ) m —NH—C(═O)—(C 1-3 -alkyl), —N(C 1-2 -alkyl)-C(═O)—(C 1-2 -alkyl), —N(C 1-2 -alkyl)-C(═O)—NH 2 , —NH—C(═O)—NH—(C 1-2 -alkyl), heterocyclyl and phenyl,
wherein each alkyl group or sub-group is optionally substituted with 1 to 3 F atoms or with one OH or —O—(C 1-2 -alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinylpiperidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of oxo, —C(═O)—CH 3 and —C(═O)-cyclopropyl; and
wherein m is 0 or 1; and
wherein multiple R 1 may be identical or different, if n is 2;

or a salt thereof.

3. The compound of formula (I) according to claim 2 , wherein
R 1 is selected from the group consisting of:
H, F, —OH, —CH 3 , —CF 3 , —O—CH 3 , —COOH, —(CH 2 ) m —C(═O)—O—CH 3 , —(CH 2 ) m —C(═O)—NH 2 , —C(═O)—NH—(C 1-3 -alkyl), —(CH 2 )—C(═O)—N(CH 3 ) 2 , —(CH 2 )—C(═O)—N(CH 3 )(CH 2 CH 3 ), —C(═O)—NH-cyclopropyl, 1-(cyclopropylcarbonyl)-piperidin-4-yl and 3-methyl-2-oxo-imidazolidin-1-yl,
wherein each ethyl group or sub-group in said R 1 group is optionally substituted in position 2 with one F atom, one OH or one —O—CH 3 group; and
wherein each propyl group or sub-group in said R 1 group is optionally substituted in position 2 or 3 with 1 to 3 F atoms; and
wherein m is 0 or 1; and

wherein, if n is 2, multiple R 1 may be identical or different and the second R 1 group is selected from the group consisting of F, CH 3 , CF 3 and phenyl;
or a salt thereof.

4. The compound of formula (I) according to claim 1 , wherein
ring A is

R 1 is selected from the group consisting of H, F, —OH, C 1-4 -alkyl, —O—(C 1-4 -alkyl), —(CH 2 ) m —COOH, —(CH 2 ) m —C(═O)—O—(C 1-4 -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 , —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 sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C 1-3 -alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of oxo, C 1-3 -alkyl, —C(═O)—CH 3 and —C(═O)-cyclopropyl; and
wherein multiple R 1 may be identical or different, if n is 2; and

n is an integer selected from 1 and 2; and
m is an integer selected from 0 and 1; and
or a salt thereof.

5. The compound of formula (I) according to claim 4 , wherein
R 1 is selected from the group consisting of:
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), —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—C 3-6 -cyclopropyl, —C(═O)—NH-heterocyclyl, —(CH 2 ) m —NH—C(═O)—(C 1-3 -alkyl), —N(CH 3 )—C(═O)—(C 1-2 -alkyl), —N(CH 3 )—C(═O)—NH 2 , —NH—C(═O)—NH—(C 1-3 -alkyl), heterocyclyl and phenyl,
wherein each alkyl group or sub-group is optionally substituted with 1 to 3 F atoms or with one OH or —O—CH 3 group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of oxo, C 1-3 -alkyl and —C(═O)—CH 3 ; and
wherein, if n is 2, multiple R 1 may be identical or different, the second R 1 group is selected from the group consisting of CH 3 , CF 3 and phenyl;

or a salt thereof.

6. The compound of formula (I) according to claim 1 , wherein
ring A is

R 1 is selected from the group consisting of H, F, Cl, —OH, —O—(C 1-4 -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),
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C 1-3 -alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one oxo or C 1-3 -alkyl group; and
wherein, if n is 2, multiple R 1 may be identical or different and the second R 1 group is F; and

n is an integer selected from 1 and 2; and
m is an integer selected from 0 and 1; and
or a salt thereof.

7. The compound of formula (I) according to claim 1 , wherein
ring A is

R 1 is selected from the group consisting of H, —(CH 2 ) m —COOH, —(CH 2 ) m —C(═O)—O—(C 1-4 -alkyl), —C(═O)-heterocyclyl, —(CH 2 ) m —C(═O)—NH 2 , —(CH 2 ) m —C(═O)—NH—(C 1-4 -alkyl) and —(CH 2 ) m —C(═O)—N(C 1-4 -alkyl) 2 ,
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C 1-3 -alkyl) group; and
wherein each heterocyclyl is selected from the group consist

Assignees

• Boehringer Ingelheim Int

Inventors

• Hehn Joerg P
• Blum Andreas
• Hucke Oliver
• Peters Stefan

Classifications

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title