Substituted pyrrolo[1,2-b]pyridazines as anthelmintics

Patent metadata

Field	Value
Publication number	US-12503474-B2
Application number	US-202418622428-A
Country	US
Kind code	B2
Filing date	Mar 29, 2024
Priority date	Nov 1, 2021
Publication date	Dec 23, 2025
Grant date	Dec 23, 2025

Abstract

This invention provides for compounds of the formula:

wherein the variables are defined herein, or salt thereof, compositions comprising these compounds, and methods for the treatment, control and/or prevention of a parasitic infestation and/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 prevention, control, and/or treatment of a parasitic infection in an animal in need thereof, wherein the method comprises administering to the animal an effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
each is independently a single bond or double bond;
R 1 is H, halogen, CN, alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), Si(alkyl) 3 , NR a R b , OH, O(alkyl), O(alkenyl), O(alkynyl), OSi(alkyl) 3 , O(aryl), SF 5 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, cycloalkoxy, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), Si(alkyl) 3 , O(alkyl), O(alkenyl), O(alkynyl), O(aryl), OSi(alkyl) 3 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, cycloalkoxy, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected substituents;
R 1 ′ is H, halogen, alkyl, or haloalkyl;
R 2 is H, halogen, CN, alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NR a R b , OH, O(alkyl), O(aryl), SF 5 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, cycloalkoxy, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), O(alkyl), O(aryl), S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, cycloalkoxy, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected substituents;
R 3 is H, halogen, CN, alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NR a R b , OH, O(alkyl), O(aryl), SF 5 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, cycloalkoxy, heterocyclyl, aryl, or heteroaryl, wherein the alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), O(alkyl), O(aryl), S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, cycloalkoxy, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more independently selected substituents;
R 4 is H, alkyl, alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NR a R b , SF 5 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, carbocyclyl-(spirocyclic carbocyclyl), carbocyclyl-(spirocyclic heterocyclyl), heterocyclyl, heterocyclyl-(spirocyclic carbocyclyl), heterocyclyl-(spirocyclic heterocyclyl), aryl, or 5- to 10-membered heteroaryl, wherein the alkyl, alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more independently selected substituents;
each R a is independently H or alkyl, wherein each alkyl is optionally and independently substituted with one or more independently selected substituents;
each R b is independently H or alkyl, wherein each alkyl is optionally and independently substituted with one or more independently selected substituents; or
any R a and R b , taken together with the nitrogen atom to which they are attached, independently forms a 3- to 8-membered heterocyclyl;
wherein each 3- to 8-membered heterocyclyl independently contains 0, 1, 2, or 3 additional heteroatoms independently selected from the group consisting of N, O, Si, and S; and
wherein each 3- to 8-membered heterocyclyl is optionally and independently substituted with one or more independently selected substituents;

L is (L1), (L2), (L3), (L4), (L5), (L6), (L7), (L8), (L9), (L10), (L11), (L12), (L13), (L14), (L15), (L16), or (L17):
—C(X)NR′-(L1), —NR′C(X)-(L2), —NR′C(X)NR′-(L3), —S(NR′) (O)CH 2 -(L4), —CH 2 S(NR′) (O)-(L5), —S(O) 2 NR′-(L6), —NR'S(O) 2 -(L7), —S(O) 2 CH 2 -(L8), —CH 2 S(O) 2 -(L9), —CH(CF 3 )NR′-(L10), —NR′CH(CF 3 )-(L11), —CH(CHF 2 )NR′-(L12), —NR′CH(CHF 2 )-(L13),

each X is independently NR′, O, or S;
R′ is H, alkyl, haloalkyl, cycloalkyl, aralkyl, or aryl, wherein the alkyl, haloalkyl, cycloalkyl, aralkyl, or aryl is optionally substituted with one or more independently selected substituents; or
two R′, together with the atoms to which they are attached, form a 2- to 4-membered carbon chain resulting in a 5- to 7-membered heterocyclyl;
Y 1 is C, CR 5 , or N;
Y 2 is CR 5 , —CR 5 R 5 ′—, N, —NR′—, —O—, or —S—;
Y 3 is CR 5 , —CR 5 R 5 ′—, N, —NR′—, —O—, or —S—;
Y 4 is CR 5 , —CR 5 R 5 ′—, N, —NR′—, —O—, or —S—;
Y 5 is CR 5 , —CR 5 R 5 ′—, N, —NR′—, —O—, or —S—;
Y 6 is C, CR 5 , or N;
W is absent, CR 6 , —CR 6 R 7 —, N, —NR 8 —, —O—, or —S(O) p —;
W 1 is CR 6 , —CR 6 R 7 , N, —NR 8 —, —O—, or —S(O) p —;
Z is CR 7 , —CR 6 R 7 —, N, —NR 8 —, —O—, or —S(O) p —;
Q is CR 9 or N;
each R 5 is independently H, halogen, CN, NO 2 , alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NR c R d , NHC(O)alkyl, OH, O(alkyl), OC(O)alkyl, SF 5 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkoxy, aryl, or heteroaryl, wherein each alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NHC(O)alkyl, O(alkyl), OC(O)alkyl S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkoxy, aryl, and heteroaryl is optionally and independently substituted with one or more independently selected substituents;
each R 5 ′ is independently H, halogen, CN, NO 2 , alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NR c R d , NHC(O)alkyl, OH, O(alkyl), OC(O)alkyl, SF 5 , S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkoxy, aryl, or heteroaryl, wherein each alkyl, alkyl-NH 2 , alkyl-NH(alkyl), alkyl-N(alkyl) 2 , alkyl-O(alkyl), alkenyl, alkynyl, C(O)alkyl, C(O)NH 2 , C(O)NH(alkyl), C(O)N(alkyl) 2 , C(O)O(alkyl), NHC(O)alkyl, O(alkyl), OC(O)alkyl, S(O) p alkyl, S(O) p haloalkyl, cycloalkyl, cycloalkoxy, aryl, and heteroaryl is optionally and independently substituted with one or more independently selected substituents; or
any R 5 and R 5 ′, taken together with the carbon atom to which they are attached, independently forms a 2- to 6-membered chain resulting in a 3- to 7-membered carbocyclyl or heterocyclyl;
wherein each 3- to 7-membered carbocyclyl or heterocyclyl optionally and independently contains 1 or 2 heteroatoms independently selected from the group consisting of N, O, Si, and S; and
wherein each 3- to 7-membered carbocyclyl or heterocyclyl is optionally and independently substituted with one or more independently selected substituents;

each R c is independently H or alkyl, wherein each alkyl is optionally and independently substituted with one or more independently selected substituents;
each R d is independently H or alkyl, wherein each alkyl is optionally and

Assignees

• Boehringer Ingelheim Vetmedica Gmbh

Inventors

• Koolman Hannes Fiepko
• Herlé Bart

Classifications

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D491/052

  the oxygen-containing ring being six-membered · CPC title

• A61P33/10

  Anthelmintics · CPC title

• A61K31/5025

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title