Bicyclic pyrazole derivatives

Patent metadata

Field	Value
Publication number	US-11130768-B2
Application number	US-201816608744-A
Country	US
Kind code	B2
Filing date	Apr 23, 2018
Priority date	Apr 27, 2017
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

The present invention covers bicyclic pyrazole compounds of general formula (I): in which G, A, R1, R2, R3, 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 and Y are independently selected from the group consisting of CR 6 R 7 , O, S, and N—R 8 , wherein at least one of X and Y is CR 6 R 7 , or
X and Y form together a group selected from —C(O)—O—, —C(O)—NR 8 —, —S(O)—NR 8 —, —SO 2 —NR 8 —, and —SO 2 —O—,
G is S,
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 , —C(O)—NH(C 3 -C 6 -cycloalkyl), —C(O)—N(C 1 -C 4 -alkyl)(C 3 -C 6 -cycloalkyl), —NR 9 R 10 , —OR 11 , —SR 12 , —S(O)R 12 , —SO 2 R 12 , 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 , —NH(C 3 -C 6 -cycloalkyl), —N(C 1 -C 4 -alkyl)(C 3 -C 6 -cycloalkyl), —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 , —NH(C 3 -C 6 -cycloalkyl), —N(C 1 -C 4 -alkyl)(C 3 -C 6 -cycloalkyl), —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 , —NH(C 3 -C 6 -cycloalkyl), —N(C 1 -C 4 -alkyl)(C 3 -C 6 -cycloalkyl), —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 , —NH(C 3 -C 6 -cycloalkyl), —N(C 1 -C 4 -alkyl)(C 3 -C 6 -cycloalkyl), —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 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 -alkyl-C(O)—, —NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , —NH(C 3 -C 6 -cycloalkyl), —N(C 1 -C 4 -alkyl)(C 3 -C 6 -cycloalkyl), —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, and —SO 2 —C 1 -C 4 -alkyl,
R 4 is selected from the group consisting of hydrogen, —OH, C 1 -C 4 -alkyl, and C 1 -C 4 -alkoxy,
R 5 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, and C 1 -C 4 -alkoxy,
or R 4 and R 5 form, together with the carbon atom to which they are attached, a 3- to 6-membered ring selected from the group consisting of C 3 -C 6 -cycloalkyl and 3- to

Assignees

• Bayer Animal Health Gmbh

Inventors

• Griebenow Nils
• Zhuang Wei
• Kulke Daniel
• Köhler Adeline
• Ilg Thomas
• Welz Claudia
• Schwarz Hans-Georg
• Görgens Ulrich
• Hübsch Walter
• Köbberling Johannes

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07D513/00 Primary

  Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 · CPC title

• A61P33/10

  Anthelmintics · CPC title

• A61K31/429

  condensed with heterocyclic ring systems · CPC title

• C07D513/14 Primary

  Ortho-condensed systems · CPC title