Quinoline derivatives for treating infections with helminths

Patent metadata

Field	Value
Publication number	US-11254661-B2
Application number	US-201816636276-A
Country	US
Kind code	B2
Filing date	Jul 30, 2018
Priority date	Aug 4, 2017
Publication date	Feb 22, 2022
Grant date	Feb 22, 2022

Abstract

The present invention covers quinoline compounds of general formula (I), in which A, R1, R2, R3, R4, R5, R6, and Q are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein:
A is A1 or A2

o is 0, 1, 2, 3 or 4;
R is selected from the group consisting of hydrogen, halogen, cyano, nitro, —OH, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl, —S(O)—C 1 -C 4 -halogenoalkyl and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms;
X, Y are independently selected from the group consisting of CR 7 R 8 , O, S, and N—R 9 , wherein at least one of X and Y is CR 7 R 8 ; or
X and Y are taken together to form a ring member selected from the group consisting of —C(O)—O—, —C(O)—NR 9 —, —S(O)—NR 9 —, —SO 2 —NR 9 — and —SO 2 —O—;
R 1 is selected from the group consisting of hydrogen, cyano, —CHO, —OH, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halogenocycloalkyl having 1 to 5 halogen atoms, C 3 -C 4 -alkenyl, C 3 -C 4 -alkynyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl-C 1 -C 3 -alkyl, cyano-C 1 -C 4 -alkyl, —NH—C 1 -C 4 -alkyl, —N(C 1 -C 4 -alkyl) 2 , NH 2 —C 1 -C 4 -alkyl-, C 1 -C 4 -alkyl-NH—C 1 -C 4 -alkyl-, (C 1 -C 4 -alkyl) 2 N—C 1 -C 4 -alkyl-, C 1 -C 4 -alkyl-C(O)—, C 1 -C 4 -halogenoalkyl-C(O)— having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy-C(O)—, benzyloxy-C(O)—, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl-C(O)—, —SO 2 —C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms,
 phenyl-C 1 -C 4 -alkyl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, —OH, —NO 2 , cyano, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —S(O)—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms and
 heterocyclyl-C 1 -C 4 -alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, —OH, —NO 2 , cyano, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —S(O)—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms;
R 2 is selected from the group consisting of
 hydrogen, halogen, cyano, —COOH, C 1 -C 4 -alkoxy-C(O)—, —C(O)—NH 2 , —C(O)—NH(C 1 -C 4 -alkyl), —C(O)—N(C 1 -C 4 -alkyl) 2 ,
 —NR 12 R 13 ,
 —OR 14 ,
 —SR 15 , —S(O)R 15 , —SO 2 R 15 ,
 C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 4 -alkenyl, C 3 -C 6 -cycloalkenyl, C 2 -C 4 -alkynyl, phenyl-C 1 -C 4 -alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, —OH, —NO 2 , cyano, C 1 -C 4 -alkyl-C(O)—, C 1 -C 4 -alkoxy-C(O)—, —C(O)—NH 2 , —C(O)—NH(C 1 -C 4 -alkyl), —C(O)—N(C 1 -C 4 -alkyl) 2 , C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —S(O)—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms,
 heterocyclyl-C 1 -C 4 -alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, —OH, —NO 2 , cyano, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —S(O)—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms,
 phenyl which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, —OH, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —S(O)—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and
 a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, cyano, nitro, —OH, oxo, thiono, —COOH, C 1 -C 4 -alkoxy-C(O)—, —C(O)—NH 2 , —C(O)—NH(C 1 -C 4 -alkyl), —C(O)—N(C 1 -C 4 -alkyl) 2 , C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-C(O)—, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl-, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, C 3 -C 6 -cycloalkyl, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, —S—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —S(O)—C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and 4- to 10-membered heterocycloalkyl;
R 3 is hydrogen, halogen, —OH, C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy;
R 4 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, C 1 -C 4 -alkyl-C(O)—, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, and —SO 2 —C 1 -C 4 -alkyl;
R 5 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -halogenoalkoxy having 1 to 5 halogen atoms, C 1 -C 4 -alkyl-C(O)—, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, and —SO 2 —C 1 -C 4 -alkyl;
R 6 is selected from the group consisting of hydrogen, halogen, —OH, cyano, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen a

Assignees

• Bayer Animal Health Gmbh

Inventors

• Griebenow Nils
• Zhuang Wei
• Kulke Daniel
• Böhm Claudia
• Schwarz Hans-Georg
• Hübsch Walter
• Ilg Thomas

Classifications

• C07D413/04

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

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07D405/14 Primary

  containing three or more hetero rings · CPC title

• A61P33/10

  Anthelmintics · CPC title

• C07D215/54

  attached in position 3 · CPC title