Anthelmintic compounds and compositions and method of using thereof

Patent metadata

Field	Value
Publication number	US-9249102-B2
Application number	US-201314083879-A
Country	US
Kind code	B2
Filing date	Nov 19, 2013
Priority date	Nov 20, 2012
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

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 2 , X 3 , X 4 , X 5 , X 6 , X 7 and X 8 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 (I):

wherein:
Y is a bicyclic carbocyclic or a bicyclic heterocyclic group optionally substituted by one or more of halogen, nitro, cyano, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl or phenyl; and Z is phenyl optionally substituted with one or more substituents independently selected from selected from the group consisting of halogen, nitro, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 halothio, C 1 -C 4 haloalkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl, phenyl, C 1 -C 4 alkylcarbonyl or C 1 -C 4 haloalkylcarbonyl;
X 1 is a bond, —C(O)—, or —CH 2 — wherein —(CH 2 ) n the —CH 2 — group is optionally substituted with alkyl;
X 2 is a 1,4-piperazinyl linker optionally substituted with one or two alkyl groups;
X 3 is a diradical group;
X 4 is —CH 2 —, wherein the —CH 2 — is optionally substituted with alkyl;
X 5 is a bond;
X 6 is —O—;
X 7 is 1,4-trans-cyclohexylenyl; and
X 8 is —NH— optionally substituted with alkyl.

2. The compound of claim 1 , wherein Y is optionally substituted naphthyl, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl, dihydroisoindolyl, dihydroquinazolinyl or tetrahydroquinolinyl.

3. The compound of claim 1 , wherein
X 2 is L1, L13, L14 or L15:

wherein R 5 and R 6 are independently hydrogen or C 1 -C 3 -alkyl.

4. A composition for the treatment of a parasitic infection or infestation in an animal, comprising an effective amount of at least one anthelmintic compound of any one of claims 1 to 3 in combination with a pharmaceutically acceptable carrier.

5. The composition of claim 4 , wherein the composition comprises an additional parasiticidal active agent.

6. A method for the treatment of a parasitic infection or infestation in an animal, comprising administering an effective amount of the compound of any one of claims 1 to 3 to the animal.

7. The compound of claim 3 , wherein X 2 is L1.

8. The compound of claim 3 , wherein X 8 is unsubstituted —NH—; and X 4 is unsubstituted —CH 2 —.

9. The compound of claim 7 , wherein:
X 1 is a bond or —CH 2 —;
X 4 is unsubstituted —CH 2 —;
X 8 is —NH— or —N(CH 3 )—;
Y is optionally substituted benzothiazolyl, benzoxazolyl or quinolinyl; and
Z is phenyl substituted with one or two C 1 -C 4 haloalkyl, halogen, nitro, cyano or C 1 -C 4 haloalkylsulfonyl.

10. The compound of claim 1 or 3 , wherein Y is optionally substituted naphthyl, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl, dihydroisoindolyl, dihydroquinazolinyl or tetrahydroquinolinyl.

11. The compound of claim 10 , wherein Y is optionally substituted indolyl, benzothiazolyl, benzoxazolyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, benzopyranyl, indazolyl, dihydroisoindolyl, dihydroquinazolinyl or tetrahydroquinolinyl; and Z is phenyl optionally substituted with one or more of halogen, nitro, cyano, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, halothio, C 1 -C 4 alkylthio, C 1 -C 4 haloalkylthio or C 1 -C 4 haloalkylsulfonyl.

12. The compound of claim 11 , wherein Y is indolyl, benzothiazolyl, benzoxazolyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, benzopyranyl, indazolyl, dihydroisoindolyl, dihydroquinazolinyl or tetrahydroquinolinyl optionally substituted with one or more halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, halothio, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl and alkylsulfonyl.

13. The compound of claim 12 , wherein Y is indolyl, benzothiazolyl, benzoxazolyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, benzopyranyl, indazolyl, dihydroisoindolyl, dihydroquinazolinyl or tetrahydroquinolinyl optionally substituted with one or more halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio or SF 5 ; and Z is phenyl optionally substituted with one or more of halogen, nitro, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkoxy.

14. The compound of claim 13 , wherein Y is indolyl, benzothiazolyl, benzoxazolyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuranyl, dihydrobenzofuranyl, benzopyranyl, indazolyl, dihydroisoindolyl, dihydroquinazolinyl or tetrahydroquinolinyl optionally substituted with one or more F, Cl, Br, methyl, CF 3 , OCH 3 , OCF 3 , SF 5 or SCF 3 ; and Z is phenyl optionally substituted with one or more of F, Cl, Br, nitro, cyano, methyl, CF 3 , OCH 3 or OCF 3 .

15. The compound of claim 14 , wherein Y is benzothiazolyl, benzoxazolyl or quinolinyl substituted with one or more F, Cl, Br, CF 3 , OCF 3 , SF 5 or SCF 3 ; and Z is phenyl substituted with two to four substituents selected from the group consisting of F, Cl, Br, nitro, cyano, methyl, CF 3 , OCF 3 or SCF 3 .

16. The compound of claim 7 , wherein:
X 1 is a bond;
X4 is unsubstituted —CH 2 —;
X 8 is —NH— or —N(CH 3 )—.

17. The compound of claim 3 , wherein the compound is selected from the group consisting of:

#
Y
X 1
X 2
X 4
X 8
Z

14

bond
L1
—CH 2 —
NH

17

Assignees

• Merial Inc
• Merial Inc

Inventors

• Meng Charles Q
• Long Alan
• Gurrala Srinivas Reddy
• Wilkinson Douglas Edward

Classifications

• A61P33/10

  Anthelmintics · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• C07D217/06

  with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D263/58

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2 · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title