Anthelmintic heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-12312356-B2
Application number	US-202418421660-A
Country	US
Kind code	B2
Filing date	Jan 24, 2024
Priority date	May 29, 2020
Publication date	May 27, 2025
Grant date	May 27, 2025

Abstract

This invention provides for compounds of the formula:

wherein the variables are defined herein, or salt thereof, compositions comprising these compounds, and method for the treatment, control or prevention of a parasitic infestation or infection in an animal in need thereof by administering an effective amount of these compounds to said animal.

First claim

What is claimed is:

1. A method for the treatment, control and/or prevention of an endoparasitic infection in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula (I):

wherein:

L is L1 or L2:

R′ is hydrogen or optionally substituted alkyl;
R 1 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted alkylaminoalkyl, optionally substituted dialkylaminoalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, or —NR a R b , wherein R a and R b are independently H or optionally substituted alkyl; or R a and R b may form, with the nitrogen to which they are attached, a 3-, 4-, 5-, 6-, 7-, or 8-membered-heterocyclyl group, which may include one to three additional heteroatoms selected from the group consisting of N, O, Si and S and may be optionally substituted;
R 2 is hydrogen, cyano, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, or optionally substituted dialkylaminocarbonyl;
R 3 is optionally substituted 6- to 10-membered aryl or optionally substituted 5- to 10-membered heteroaryl;
R 4 is independently in each occurrence hydrogen, halogen, cyano, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylcarbonyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted di(alkyl)aminocarbonyl, optionally substituted alkylcarbonyloxy or optionally substituted alkylcarbonylamino;
R 5 and R 6 are independently in each occurrence hydrogen or C 1 -C 4 -alkyl;
R 7 is hydrogen or C 1 -C 4 -alkyl;
R 8 is hydrogen or optionally substituted alkyl;
R 9 and R 9′ are independently hydrogen or C 1 -C 4 -alkyl; or R 9 together with R 9′ form a 2-6-membered chain optionally containing one or two heteroatoms selected from the group consisting of N, O, Si and S to form carbocyclic or heterocyclic ring together with the carbon atom to which they are attached;
Q is C—R 8 ;
X is O;
Y 1 and Y 6 are each independently N or C;
Y 2 , Y 3 , Y 4 and Y 5 are each independently N, S or —CR 4 —;
W is CR 5 R 6 ,
Z is CR 5 R 6 , O, SO p , or N—R 7 ; and
wherein at most three of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 are heteroatoms;
a is 0 or 1;
q is 0 or 1;
p is independently in each occurrence is 0, 1, or 2; and
the dashed bonds ( ) signifies a single or double bond;

or a pharmaceutically acceptable salt thereof;
wherein each optional substituent is independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, cyano, hydroxyl, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, thiol, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl and C 1 -C 6 -haloalkylsulfonyl.

2. The method of claim 1 , wherein R 3 is optionally substituted phenyl or optionally substituted pyridyl.

3. The method of claim 1 , wherein the compound of Formula (I) is a compound of formula (Ie):

wherein:
R 1 is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, hydroxy-C 1 -C 4 -alkyl, alkoxy-C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -haloalkenyl, or —NR a R b wherein R a and R b are independently H, C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl; or R a and R b form, with the nitrogen to which they are attached, a 3-, 4-, 5- or 6-membered-heterocyclyl group, which may include one to three additional heteroatoms selected from the group consisting of N, O and S and may be optionally substituted;
R 2 is hydrogen, halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;
each R 4 is independently hydrogen, halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, or C 1 -C 4 -haloalkoxy;
R 5 and R 6 are independently hydrogen, or C 1 -C 3 -alkyl;
R′ is hydrogen or C 1 -C 3 -alkyl;
R 8 is hydrogen;
R 9 and R 9′ are independently hydrogen or C 1 -C 3 -alkyl;
each R 10 is independently halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, or C 1 -C 4 -haloalkoxy;
Z is CR 5 R 6 or O;
Y 2 , Y 3 , Y 4 , Y 5 are independently CR 4 or N;
a is 0 or 1; and
m is 0, 1, 2, or 3.

4. The method according to claim 3 , wherein each R 10 is independently halogen and m is 2 or 3.

5. The method according to claim 3 , wherein each R 10 is independently chloro or fluoro; and
m is 2 or 3.

6. The method of claim 3 , wherein:
R′ is hydrogen;
each R 4 is independently hydrogen, halogen or cyano;
R 5 and R 6 are independently hydrogen or C 1 -C 3 -alkyl;
R 9 and R 9′ are independently hydrogen or C 1 -C 3 -alkyl;
each R 10 is independently halogen;
W is CH 2 ;
Z is O;
Y 2 , Y 3 , Y 4 , Y 5 are independently CR 4 or N;
a is 0 or 1; and
m is 2 or 3.

7. The method according to claim 6 , wherein:
R 1 is C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl or —NR a R b ;
R 2 is hydrogen, halogen, C 1 -C 3 -alkyl or C 1 -C 3 -haloalkyl; and
each R 10 is independently chloro or fluoro.

8. The method according to claim 7 , wherein:
R 1 is C 1 -C 4 -alkyl or hydroxy-C 1 -C 4 -alkyl;
R 2 is C 1 -C 3 -alkyl.

9. The method according to claim 7 , wherein:
R 1 is —NR a R b ;
R a and R b are independently H or C 1 -C 4 -alkyl; or R a and R b form, with the nitrogen to which they are attached, a 3-, 4-, 5- or 6-membered heterocyclyl group, which may include one or two additional heteroatoms selected from the group consisting of N, O and S and is optionally substituted with one or more halogen, hydroxyl or C 1 -C 3 -alkyl; and
R 2 is C 1 -C 3 -alkyl.

10. The method according to claim 9 , wherein:
R a and R b are independently C 1 -C 3 -alkyl.

11. The method according to claim 9 , wherein:
R a and R b form with the nitrogen to which they are attached a 3-, 4-, 5- or 6-membered ring which is optionally substituted with one or more halogen, hydroxyl or C 1 -C 3 -alkyl.

12. A method for the treatment, control and/or prevention of an endoparasitic infection in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula (I):

wherein R 1 , R 2 , R 3 and L are shown in the table below;
L1 is:

wherein X is oxygen and R′ is hydrogen;

L2 is:

wherein X is oxygen and R′ is hydrogen;
“Me” is methyl;
“i-Pr” is isopropyl;
“t-Bu” is tert-butyl;
prop-1-en-2-yl is

Assignees

• Boehringer Ingelheim Vetmedica Gmbh
• Boehringer Ingelheim Pharma

Inventors

• Koolman Hannes Fiepko
• Herlé Bart
• Long Alan

Classifications

• A61P33/10

  Anthelmintics · CPC title

• A01P7/04

  Insecticides · CPC title

• A01P7/02

  Acaricides · CPC title

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title

• A61P33/00

  Antiparasitic agents · CPC title