Pyrazolopyrimidine derivatives

Patent metadata

Field	Value
Publication number	US-10604525-B2
Application number	US-201716093565-A
Country	US
Kind code	B2
Filing date	Apr 10, 2017
Priority date	Apr 15, 2016
Publication date	Mar 31, 2020
Grant date	Mar 31, 2020

Abstract

The present invention covers Pyrazolopyrimidine compounds of general formula (I), in which n, o, X, Y, R, Q, R 1 , R 2 , R 3 and R 4 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:
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;
n is 0 or 1;
X and Y are independently selected from the group consisting of CR 5 R 6 , O, S, and N—R 7 , wherein at least one of X and Y is CR 5 R 6 ;
R 1 is selected from the group consisting of hydrogen, —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, amino-C 1 -C 4 -alkyl, C 1 -C 4 -alkylamino-C 1 -C 4 -alkyl, di-(C 1 -C 4 -alkyl)amino-C 1 -C 4 -alkyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -halogenoalkylcarbonyl having 1 to 5 halogen atoms, C 1 -C 4 -alkoxycarbonyl, benzyloxycarbonyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkylcarbonyl, —SO 2 —C 1 -C 4 -alkyl, and —SO 2 —C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms;
R 2 is hydrogen, halogen, cyano, —CHO, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, 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, benzyl 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), —NH(4- to 7-membered heterocycloalkyl), —N(C 1 -C 4 -alkyl)(4- to 7-membered heterocycloalkyl), —NH(C 1 -C 4 -alkoxy), —N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy), —NH—SO 2 —(C 1 -C 4 -alkyl), —N(SO 2 —[C 1 -C 4 -alkyl])(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-, —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, (C 1 -C 4 -alkoxyimino)-C 1 -C 4 -alkyl, or a monocyclic heterocycle selected from the group consisting of 4- to 7-membered heterocycloalkyl, 5-membered heteroaryl having at least one nitrogen atom via which the heteroaryl ring is connected to the rest of the molecule, and 6-membered heteroaryl having at least one nitrogen atom, each of which monocyclic heterocycle in R 2 is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, —OH, oxo, thiono, 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, and wherein each C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl and C 1 -C 4 -alkoxy in R 2 is optionally substituted with halogen, OH, NH 2 , —NH(C 1 -C 4 -alkyl), —N(C 1 -C 4 -alkyl) 2 , cyano, carboxy, carbamoyl, alkoxycarbonyl, —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 1 -C 4 -alkoxy, —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, or —SO 2 —C 1 -C 4 -alkyl, or optionally substituted by a monocyclic heterocycle selected from the group consisting of 4- to 7-membered heterocycloalkyl and a 5-membered heteroaryl having at least one nitrogen atom via which the heteroaryl ring is connected to the C 1 -C 4 -alkyl, or C 3 -C 6 -cycloalkyl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, —OH, oxo, thiono, 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;
R 3 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, and C 3 -C 6 -cycloalkyl;
R 4 is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms, 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 5 is selected from the group consisting of hydrogen, fluorine and C 1 -C 4 -alkyl;
R 6 is selected from the group consisting of hydrogen, fluorine and C 1 -C 4 -alkyl;
R 7 is selected from the group consisting of hydrogen and C 1 -C 4 -alkyl; and
Q is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl, each of which is optionally substituted with 1, 2, 3, 4 or 5 substituents,

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of any of the foregoing.

2. The compound according to claim 1 , wherein:
o is 0, 1, 2, 3 or 4;
R is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl and C 1 -C 4 -halogenoalkyl having 1 to 5 halogen atoms;
n is 0 or 1;
X and Y are independently selected from the group consisting of CR 5 R 6 , O, S, and N—R 7 , wherein at least one of X and Y is CR 5 R 6 ;
R 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 3 -C 4 -alkenyl, C 3 -C 4 -alkynyl, and C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl;
R 2 is hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkinyl, 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, benzyl 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), —NH(4- to 7-membered heterocycloalkyl), —N(C 1 -C 4 -alkyl)(4- to 7-membered heterocycloalkyl), —NH(C 1 -C 4 -alkoxy), —N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy), —NH—SO 2 —(C 1 -C 4 -alkyl), —N(SO 2 —[C 1 -C 4 -alkyl])(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-, —S—C 1 -C 4 -alkyl, —S(O)—C 1 -C 4 -alkyl, —SO 2 —C 1 -C 4 -alkyl, (C 1 -C 4 -alkoxyimino)-C 1 -C 4 -alkyl, or a monocyclic heterocycle selected from the group consisting of 4- to 7-membered heterocycloalkyl, 5-membered heteroaryl having at least one nitrogen atom via which the heteroaryl ring is connected to the rest of the molecule, and 6-membered heteroaryl having at least one nitrogen atom, each of which monocyclic heterocycle in R 2 is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of hydrogen, halogen, cyano, nitro, —OH, oxo, thiono, 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, and wherein each C 1 -C 4

Assignees

• Bayer Animal Health Gmbh
• Bayal Animal Health Gmbh

Inventors

• Köhler Adeline
• Welz Claudia
• Börngen Kirsten
• Kulke Daniel
• Ilg Thomas
• Köbberling Johannes
• Hübsch Walter
• Schwarz Hans-Georg
• Görgens Ulrich
• Ebbinghaus-Kintscher Ulrich
• Hink Maike
• Nennstiel Dirk
• Raming Klaus
• Adamczewski Martin
• Böhm Claudia
• Griebenow Nils
• Zhuang Wei

Classifications

• C07D487/02 Primary

  in which the condensed system contains two hetero rings · CPC title

• A61P33/10

  Anthelmintics · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/5377

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