Modulators of complex I

Patent metadata

Field	Value
Publication number	US-11795147-B2
Application number	US-202017002937-A
Country	US
Kind code	B2
Filing date	Aug 26, 2020
Priority date	Aug 26, 2019
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

The present invention describes compounds modulating the function of mitochondrial complex I (NADH-quinone oxidoreductase) having formula (I)

First claim

The invention claimed is:

1. A compound having formula (I) or a salt thereof

wherein:
R1 is C 1-4 -alkyl unsubstituted or substituted with MeO; tetrahydropyranyl, tetrahydrofuranyl, oxetanyl, dioxepanyl, pyrrolidinyl or piperidinyl; or
pyrrolidinyl or piperidinyl with the nitrogen substituted by methyl, isopropyl, oxetanyl, ethoxycarbonyl, acetyl, or trifluoroacetyl;

R2 is a 5-, 6- or 7-membered ring containing 1 or 2 heteroatoms selected from O or N bound in formula (I) by a C═C double bond,
in which one or both N-atoms can be substituted by methyl, isopropyl, acetyl, benzyloxycarbonyl, phenyl, oxetanyl or tetrahydropyranyl, and
in which one or more C-atoms can be substituted by -methyl or —OH;

R3 and R4 are independently from one another
hydrogen; C 1-6 -alkyl, unsubstituted or substituted with one or more F, methoxy, C 3-8 -cycloalkyl unsubstituted or substituted with one or more F; aryl; heteroaryl consisting of 5 to 6 ring atoms; or heterocyclyl selected from the group consisting of oxetanyl, tetrahydropyranyl and pyrrolidinyl, said heterocyclyl being unsubstituted or substituted with C 1-6 -alkyl, acetyl, tetrahydrofuranyl, oxetanyl or hydroxyethylacetyl;

or R3 and R4 together with the attached N form a heterocyclyl ring selected from the group consisting of morpholinyl and pyrrolidinyl both unsubstituted or substituted with C 1-6 -alkyl, F, or hydroxyl;
or R3 and R4 together represent one of the following groups:

2. A compound selected from the group consisting of the following compounds 1 to 175, or a salt thereof:

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Structure

 1

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Assignees

• Boehringer Ingelheim Int

Inventors

• Gerlach Kai
• Eickmeier Christian
• Kriegl Jan Magnus
• Kussmaul Lothar
• Rudolf Klaus
• Schmid Bernhard

Classifications

• C07D207/38 Primary

  2-Pyrrolones · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D471/08

  Bridged systems · CPC title

• C07D491/044

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D498/10

  Spiro-condensed systems · CPC title