Pyrazolopyrimidine derivatives

Patent metadata

Field	Value
Publication number	US-10934301-B2
Application number	US-202016776377-A
Country	US
Kind code	B2
Filing date	Jan 29, 2020
Priority date	Apr 15, 2016
Publication date	Mar 2, 2021
Grant date	Mar 2, 2021

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 method for control or treatment of a helminthic disease in a human or animal, the method comprising administering to a human or animal in need thereof an anthelminthically effective amount of at least one compound of formula (I)

or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of any of the foregoing, 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 -halogeno alkyl, —S(O)—C 1 -C 4 -halogeno alkyl 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.

2. The method of 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 -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 an

Assignees

• Bayer Animal Health Gmbh

Inventors

• Görgens Ulrich
• Welz Claudia
• Kulke Daniel
• Böhm Claudia

Classifications

• A61P33/10

  Anthelmintics · CPC title

• A61K31/5377

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

• A61K31/519

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

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/02 Primary

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