Anthelmintic compounds

Patent metadata

Field	Value
Publication number	US-10045979-B2
Application number	US-201515311848-A
Country	US
Kind code	B2
Filing date	May 19, 2015
Priority date	May 19, 2014
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

The present invention relates to novel anthelmintic compounds of formula (I) below:

wherein
Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X 1 , X 6 , X 8 , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , Q 6 , Ring A, Ring B, W, W′, R 2 , R 3 , R, R′, m, n and q are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.

First claim

What is claimed is:

1. An anthelmintic compound of formula (IA-1):

wherein
Y is benzothiazolyl or benzoxazolyl substituted by one or more of halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 halolakoxy, C 1 -C 3 haloalkylthio, C 1 -C 3 haloalkylthio or halothio; and Z is phenyl substituted with one or more of halogen, nitro, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 halolakoxy, C 1 -C 3 alkylthio or C 1 -C 3 haloalkylthio;
X 1 is a bond, —O—, —C(O)—, —C(S)—, —NH— or —N(alkyl)-, —S—, —S(O)—, —S(O) 2 —, —NHS(O)—, —S(O)—NH—, —NHSO 2 —, —SO 2 NH—, —(CH 2 ) n — where n is 1 to 3, —C(O)—CH 2 —, —CH 2 —C(O)—, —O—CH 2 —, —CH 2 —O—, —NHCH 2 —, —CH 2 —NH—, —S—CH 2 —, —CH 2 —S—, —S(O)—CH 2 —, —CH 2 —S(O)—, —S(O) 2 —CH 2 —, or —CH 2 —S(O) 2 —, wherein each NH, —NHS(O)—, —S(O)—NH—, —NHSO 2 —, —SO 2 NH—, —(CH 2 ) n , —C(O)CH 2 —, —CH 2 —C(O)—, —O —CH 2 —, —CH 2 —O, —NH—CH 2 , —CH 2 —NH—, —S—CH 2 —, —CH 2 —S—, —S(O)—CH 2 —, —CH 2 —S(O)—, —S(O) 2 —CH 2 — and —CH 2 —S(O) 2 — is optionally independently substituted with oxo (═O) or one or two substituents selected from the group consisting of halogen, cyano, hydroxy, hydroxyalkyl, alkoxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, alkyl, haloalkyl, cycloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl or aryl groups, where each substituent group may be further independently substituted by hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino and carboxy (—COOH);
X 6 is —O— or —NH—wherein the —NH—, is optionally substituted with, alkyl or haloalkyl;
X 8 is a bond, —(CH 2 ) n where n is 1 to 3, —O—, —C(O)—,—S—, —S(O)—, —S(O) 2 —, —NHS(O)—, —S(O)—NH—, —NHSO 2 —, —SO 2 NH—, or —NH—, wherein each CH 2 in —(CH 2 ) n —, —NHS(O)—, —S(O)—NH—, —NHSO 2 —, —SO 2 NH— or the —NH— is optionally independently substituted with one or two substituents selected from the group consisting of halogen, hydroxy, amino, alkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl, heterocyclyl, carbocyclylalkyl, heterocyclylalkyl and oxo (═O), where each substituent group may be further independently substituted by hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino or carboxy (—COOH);
one of Ring A and Ring B is L19, L20 or L21:

and the other of Ring A and Ring B is trans-cyclohexylene, L1 or L4:

where Q 1 , Q 2 , Q 5 and Q 6 are independently N or CH;
W is O or S;
R 2 and R 3 are independently hydrogen, halogen, or alkyl; and
n is 1, 2 or 3.

2. The anthelminitic compound of claim 1 , wherein:
X 1 is —NH— which is optionally substituted a substituent selected from the group consisting of hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, alkylcarbonyl, alkenylcarbonyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl, heterocyclyl, carbocyclylalkyl and heterocyclylalkyl, where each substituent may be further independently substituted by hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino or carboxy (—COOH).

3. The anthelminitic compound of claim 1 , wherein Y is benzothiazolyl or benzoxazolyl substituted with one or more of CF 3 , OCF 3 , SCF 3 ; and Z is phenyl substituted with one or more of halogen, CN or CF 3 .

4. The anthelminitic compound of claim 1 or 3 , wherein X 1 is a bond, —NH— or —NMe—.

5. The anthelminitic compound of claim 1 , wherein X 8 is a bond, —NH—, —NMe—, >N(CH 2 ) 2 NEt 2 , >NCO 2 Et or >NCO(CH 2 ) 2 CO 2 H.

6. A composition for the treatment and prevention of a parasitic infection or infestation in an animal, comprising an effective amount of at least one anthelmintic compound of claim 1 in combination with a pharmaceutically acceptable carrier.

7. The composition of claim 6 , wherein the composition comprises an additional parasiticidal active agent.

8. A method for the treatment and prevention of a parasitic infection or infestation in an animal, comprising administering an effective amount of the compound of claim 1 to the animal.

9. The anthelminitic compound of claim 4 , wherein X 8 is a bond.

10. The anthelmintic compound of claim 1 , wherein Ring A is L1.

11. The anthelmintic compound of claim 1 , wherein Ring A is L4.

12. The anthelmintic compound of claim 1 , wherein Ring B is L19.

13. The anthelmintic compound of claim 1 , wherein Ring A is L1 and Ring B is L19.

14. The anthelmintic compound of claim 1 , wherein Ring A is L4 and Ring B is L19.

15. The anthelmintic compound of claim 1 , wherein X 6 is O.

16. The anthelmintic compound of claim 1 , wherein:
Ring A is L1 or L4;
Ring B is L19;
Y is benzothiazolyl or benzoxazolyl substituted with one or more of CF 3 , OCF 3 , SCF 3 ;
Z is phenyl substituted by one or more halogen, nitro, cyano, CF 3 , OCF 3 or SCF 3 .

17. The anthelmintic compound of claim 16 , wherein X 1 is a bond.

18. The anthelmintic compound of claim 17 , wherein X 6 is O.

Assignees

• Merial Inc

Inventors

• Long Alan
• Gurrala Srinivas Reddy

Classifications

• A61P33/14

  Ectoparasiticides, e.g. scabicides · CPC title

• A61P33/10

  Anthelmintics · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K31/06

  the aromatic ring being substituted by nitro groups · CPC title