ANTHELMINTIC COMPOUNDS, COMPOSITIONS AND METHOD OF USING THEREOF

• US 20180009754A1
• Filed: 01/20/2016
• Published: 01/11/2018
• Est. Priority Date: 01/20/2015
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Animal Health USA, Inc. (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Merial Incorporated (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Long, Alan, Wilkinson, Dpuglas Edward
• Granted Patent: US 10,597,364 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 33/14 Ectoparasiticides, e.g. scabicides
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

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

• • wherein, Y is selected from the group consisting of —H, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, haloalkyl, and alkoxyalkyl; and Z is selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, haloalkyl, and alkoxyalkyl. Variables Ring A, Ring B, Ring C, X₁, X₆, and X₈ are as defined herein. The invention also relates to parasiticidal compositions comprising the compounds, and methods and uses of the compounds for treating and preventing parasitic infections and infestations in animals.

Claims

1. An anthelmintic compound of formula (IA):

2. A compound of claim 1, wherein:

Y is —

H or aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, haloalkyl, or alkoxyalkyl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, aryl, aryloxy, arylalkoxy, arylthio, arylalkylthio, arylsulfinyl, arylsulfonyl, arylalkylsulfinyl, arylalkylsulfonyl, heteroaryl, heteroaryloxy, heteroarylalkoxy, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylalkylthio, heteroarylalkylsulfinyl or heteroarylalkylsulfonyl;

Z is aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, haloalkyl, or alkoxyalkyl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, aryl, aryloxy, arylalkoxy, arylthio, arylalkylthio, arylsulfinyl, arylsulfonyl, arylalkylsulfinyl, arylalkylsulfonyl, heteroaryl, heteroaryloxy, heteroarylalkoxy, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylalkylthio, heteroarylalkylsulfinyl or heteroarylalkylsulfonyl;

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3, —

O—

CH₂—

, —

CH₂—

O—

, —

N(R¹)(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

N(R¹)—

where n is 1 to 3, —

S—

CH₂—

, —

CH₂—

S—

, —

S(O)—

CH₂—

, —

CH₂—

S(O)—

, —

S(O)₂—

CH₂—

, or —

CH₂—

S(O)₂—

;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is selected from the group consisting of monocyclic arylene, monocyclic heteroarylene, monocyclic heterocyclylene, bicyclic arylene, bicyclic heteroarylene, and bicyclic heterocyclylene optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is cycloalkylene or heterocyclylene, which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group;

X₈ is a bond, —

(CH₂)_n where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

; and

each R¹ is independently H, alkyl, or arylalkyl.

3. A compound of claim 1, wherein:

Z is aryl, or heteroaryl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is selected from the group consisting of monocyclic arylene, monocyclic heteroarylene, monocyclic heterocyclylene, bicyclic arylene, bicyclic heteroarylene, and bicyclic heterocyclylene optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is cycloalkylene or heterocyclylene, which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group; and

X₈ is a bond, —

(CH₂)_n where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

.

4. A compound of claim 1, wherein:

Ring A is a diradical group selected from the group consisting of a 3-8 membered heterocyclylene group and a 3-8 membered spirocyclic heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is a diradical group selected from the group consisting of monocyclic arylene and monocyclic heteroarylene, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

Y is —

H or aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, or haloalkyl, optionally substituted by one or more of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl; and

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, or —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3.

5. A compound of claim 1, wherein:

Z is aryl, or heteroaryl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is a diradical group selected from the group consisting of monocyclic arylene and monocyclic heteroarylene, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is cycloalkylene or heterocyclylene, which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group; and

X₈ is a bond, —

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

.

6. A compound of claim 1, wherein:

Ring A is a diradical group selected from the group consisting of a 6 membered heterocyclylene group and a 8 membered spirocyclic heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is a 6 membered monocyclic heteroarylene, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

Y is —

H or 5-6 membered aryl, 5-6 membered cycloalkyl, 5-6 membered cycloalkenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclyl, C₁₄ alkyl, or C₁₄ haloalkyl, optionally substituted by one or more of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl; and

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, or —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3.

7. A compound of claim 1, wherein:

Z is a 6 membered aryl, or a 6 membered heteroaryl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is a diradical group selected from the group consisting of monocyclic arylene and monocyclic heteroarylene, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is 4-6 membered monocyclic cycloalkylene, 4-6 membered monocyclic heterocyclylene, 7-9 membered spirocyclic cycloalkylene, 7-9 membered spirocyclic heterocyclylene which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group; and

X₈ is a bond, —

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

.

8. A compound of claim 1, wherein:

Ring A is a diradical group selected from the group consisting of a 6 membered heterocyclylene group and a 8 membered spirocyclic heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Ring C is a 6 membered monocyclic heteroarylene, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, carbocyclyl and halocarbocyclyl;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is 4-6 membered monocyclic cycloalkylene, 4-6 membered monocyclic heterocyclylene, 7-9 membered spirocyclic cycloalkylene, 7-9 membered spirocyclic heterocyclylene which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group;

X₈ is a bond, —

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

;

Y is —

H or 5-6 membered aryl, 5-6 membered cycloalkyl, 5-6 membered cycloalkenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclyl, C₁-C₄ alkyl, or C₁-C₄ haloalkyl, optionally substituted by one or more of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Z is a 6 membered aryl, or a 6 membered heteroaryl, substituted by one or more of halogen, nitro, cyano, hydroxy, alkyl, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, or —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3; and

each R¹ is independently H, or C₁-C₃ alkyl.

9. A compound of claim 1, having the structure:

10. A compound of claim 1, wherein:

Y is —

H or aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, haloalkyl, or alkoxyalkyl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, aryl, aryloxy, arylalkoxy, arylthio, arylalkylthio, arylsulfinyl, arylsulfonyl, arylalkylsulfinyl, arylalkylsulfonyl, heteroaryl, heteroaryloxy, heteroarylalkoxy, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylalkylthio, heteroarylalkylsulfinyl or heteroarylalkylsulfonyl;

Z is aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, haloalkyl, or alkoxyalkyl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, aryl, aryloxy, arylalkoxy, arylthio, arylalkylthio, arylsulfinyl, arylsulfonyl, arylalkylsulfinyl, arylalkylsulfonyl, heteroaryl, heteroaryloxy, heteroarylalkoxy, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylalkylthio, heteroarylalkylsulfinyl or heteroarylalkylsulfonyl;

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3, —

O—

CH₂—

, —

CH₂—

O—

, —

N(R¹)(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

N(R¹)—

where n is 1 to 3, —

S—

CH₂—

, —

S(O)—

CH₂—

, —

CH₂—

S(O)—

, —

S(O)₂—

CH₂—

, or —

CH₂—

S(O)₂—

;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q₁₁, Q₁₂ and Q₁₃ are each independently —

CH, —

CH₂, —

C(R⁹)R⁹, or a heteroatom selected from N, —

NH, —

NR^9′

, S or O;

the dotted lines in the ring represent single or double bonds;

each R⁹ is each independently halogen, cyano, hydroxyl, amino, alkylamino, dialkylamino, alkyl, haloalkyl, carbocyclyl, heterocyclyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

each R^9′

is each independently alkyl, or alklylaryl;

p is 0, 1 or 2;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is cycloalkylene or heterocyclylene, which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group;

X₈ is a bond, —

(CH₂)_n where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

; and

each R¹ is independently H, alkyl, or arylalkyl.

11. A compound of claim 1, wherein:

Z is aryl, or heteroaryl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q₁₁, Q₁₂ and Q₁₃ are each independently —

CH, —

CH₂, —

CHR⁹, —

C(R⁹)R⁹, or a heteroatom selected from N, —

NH, —

NR^9′

, S or O;

the dotted lines in the ring represent single or double bonds;

each R⁹ is each independently halogen, cyano, hydroxyl, amino, alkylamino, dialkylamino, alkyl, haloalkyl, carbocyclyl, heterocyclyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

each R^9′

is each independently alkyl, or alklylaryl;

p is 0, 1 or 2;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

,

Ring B is cycloalkylene or heterocyclylene, which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group; and

X₈ is a bond, —

(CH₂)_n where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

.

12. A compound of claim 1, wherein:

Ring A is a diradical group selected from the group consisting of a 3-8 membered heterocyclylene group and a 3-8 membered spirocyclic heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q₁₁, Q₁₂ and Q₁₃ are each independently —

CH, —

CH₂, —

CHR⁹, —

C(R⁹)R⁹, or a heteroatom selected from N, —

NH, —

NR^9′

, S or O;

the dotted lines in the ring represent single or double bonds;

each R⁹ is each independently halogen, cyano, hydroxyl, amino, alkylamino, dialkylamino, alkyl, haloalkyl, carbocyclyl, heterocyclyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

each R^9′

is each independently alkyl, or alklylaryl;

p is 0, 1 or 2;

Y is —

H or aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclyl, alkyl, or haloalkyl, optionally substituted by one or more of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl; and

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, or —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3.

13. A compound of claim 1, wherein:

Z is aryl, or heteroaryl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q₁₁, Q₁₂ and Q₁₃ are each independently —

CH, —

CH₂, —

CHR⁹, —

C(R⁹)R⁹, or a heteroatom selected from N, —

NH, —

NR^9′

, S or O;

the dotted lines in the ring represent single or double bonds;

each R⁹ is each independently halogen, cyano, hydroxyl, amino, alkylamino, dialkylamino, alkyl, haloalkyl, carbocyclyl, heterocyclyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

each R^9′

is each independently alkyl, or alklylaryl;

p is 0, 1 or 2;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

,

Ring B is cycloalkylene or heterocyclylene, which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group; and

X₈ is a bond, —

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

.

14. A compound of claim 1, wherein:

Ring A is a diradical group selected from the group consisting of a 6 membered heterocyclylene group and a 8 membered spirocyclic heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q₁₁, Q₁₂ and Q₁₃ are each independently —

CH, —

CH₂, —

CHR⁹, —

C(R⁹)R⁹, or a heteroatom selected from N, —

NH, —

NR^9′

, S or O;

the dotted lines in the ring represent single or double bonds;

each R⁹ is each independently halogen, cyano, hydroxyl, amino, alkylamino, dialkylamino, alkyl, haloalkyl, carbocyclyl, heterocyclyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

each R^9′

is each independently alkyl, or alklylaryl;

p is 0, 1 or 2;

Y is —

H or 5-6 membered aryl, 5-6 membered cycloalkyl, 5-6 membered cycloalkenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclyl, C₁₄ alkyl, or C₁₄ haloalkyl, optionally substituted by one or more of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl; and

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, or —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3.

15. A compound of claim 1, wherein:

Z is a 6 membered aryl, or a 6 membered heteroaryl, optionally substituted by one or more of halogen, nitro, cyano, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Ring A is a diradical group selected from the group consisting of a 3-8 membered monocyclic carbocyclylene and a 3-8 membered heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q₁₁, Q₁₂ and Q₁₃ are each independently —

CH, —

CH₂, —

CHR⁹, —

C(R⁹)R⁹, or a heteroatom selected from N, —

NH, —

NR^9′

, S or O;

the dotted lines in the ring represent single or double bonds;

each R⁹ is each independently halogen, cyano, hydroxyl, amino, alkylamino, dialkylamino, alkyl, haloalkyl, carbocyclyl, heterocyclyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl;

each R^9′

is each independently alkyl, or alklylaryl;

p is 0, 1 or 2;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

,

Ring B is 4-6 membered monocyclic cycloalkylene, 4-6 membered monocyclic heterocyclylene, 7-9 membered spirocyclic cycloalkylene, 7-9 membered spirocyclic heterocyclylene which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group; and

X₈ is a bond, —

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

.

16. A compound of claim 1, wherein:

Ring A is a diradical group selected from the group consisting of a 6 membered heterocyclylene group and a 8 membered spirocyclic heterocyclylene group, optionally substituted with one or more substituents independently selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, amino, alkylamino, dialkylamino, aminoalkyl, and oxo (═

O);

Q₉, Q₁₀, Q_ii, Q₁₂ and Q₁₃ are each independently —

CH or N;

the dotted lines in the ring represent double bonds;

X₆ is —

O—

, —

N(R¹)—

, —

N(R¹)CH₂—

, or —

CH₂N(R¹)—

;

Ring B is 4-6 membered monocyclic cycloalkylene, 4-6 membered monocyclic heterocyclylene, 7-9 membered spirocyclic cycloalkylene, 7-9 membered spirocyclic heterocyclylene which may be optionally substituted with one or more halogen, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino or aminoalkyl group;

X₈ is a bond, —

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

O—

where n is 0 or 1, —

O—

(CH₂)_n—

where n is 0 or 1, —

N(H)—

, —

N(H)CH₂—

, or —

CH₂N(H)—

;

Y is —

H or 5-6 membered aryl, 5-6 membered cycloalkyl, 5-6 membered cycloalkenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclyl, C₁-C₄ alkyl, or C₁-C₄ haloalkyl, optionally substituted by one or more of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

Z is a 6 membered aryl, or a 6 membered heteroaryl, substituted by one or more of halogen, nitro, cyano, hydroxy, alkyl, halothio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, or haloalkylsulfonyl;

X₁ is a bond, C₂-C₄ alkenylene, —

O—

, —

C(O)—

, —

O—

C(O)—

, —

C(O)—

O—

, —

N(R¹)S(O)—

, —

S(O)—

N(R¹)—

, —

N(R¹)—

C(S)—

, —

C(S)—

N(R¹)—

, —

N(R¹)SO₂—

, —

SO₂N(R¹)—

, —

N(R¹)—

C(O)—

, —

C(O)—

N(R¹)—

, —

(CH₂)_n—

where n is 1 to 3, —

C(O)—

(CH₂)_n—

where n is 1 to 3, —

(CH₂)_n—

C(O)—

where n is 1 to 3, —

O—

(CH₂)_n—

C(O)—

where n is 1 to 3, or —

C(O)—

(CH₂)_n—

O—

where n is 1 to 3; and

each R¹ is independently H, or C₁-C₃ alkyl.

17. A compound of claim 1, wherein

18. A compound of claim 1, wherein

21. A compound of claim 1 selected from the group shown in the following table:

22. A compound according to claim 1, as shown in any one of Examples 1 to 16.

23. A composition for the treatment and prevention of a parasitic infection or infestation in an animal, comprising a therapeutically effective amount of at least one anthelmintic compound of any one of claims 1 to 22 in combination with a pharmaceutically acceptable carrier.

24. The composition of claim 23, wherein the composition comprises an additional anti-parasitic agent.

25. A method for the treatment and prevention of a parasitic infection or infestation in an animal, comprising administering to the animal a therapeutically effective amount of an anthelmintic compound of any one of claims 1 to 22.

19. A compound according to any one of the proceeding claims, provided that:

when Ring C is pyrimidinyl;

Z is substituted phenyl;

X₆ is a bond, —

O—

, —

N(R¹)(CH₂)_n—

where n is 0 to 2, and Ring B is 1,4-cyclohexylene, 1,3-cyclobutylene, 1,1-cyclopropylene, piperidin-1,4-diyl, pyrrolidin-1,3-diyl, piperazin-1,4-diyl, azetidin-1,3-diyl, morpholin-2,4-diyl, then

X₈ is not a bond, —

N(R¹)(CH₂)_n—

where n is 0 to 2, —

(CH₂)_n where n is 1 to 3, —

C(O)—

, —

S(O)₂—

, —

O—

, or —

(CH₂)_n—

N(R¹)—

where n is 0 to 2;

or

when Ring C is pyrimidinyl;

Z is phenyl substituted by one or more groups selected from halogen, nitro, cyano, amino, alkylamino, dialkylamino, aminoalkyl, alkyl, haloalkyl, alkoxy, haloalkylthio, alkylsulfinyl, and haloalkylsulfinyl;

X₆ is a bond, —

O—

, —

N(R¹)(CH₂)_n—

where n is 0 to 2; and

Ring B is 1,4-cyclohexylene, 1,3-cyclobutylene, 1,1-cyclopropylene, piperidin-1,4-diyl, pyrrolidin-1,3-diyl, piperazin-1,4-diyl, azetidin-1,3-diyl, morpholin-2,4-diyl, then

X₈ is not a bond, —

N(R¹)(CH₂)_n—

where n is 0 to 2, —

(CH₂)_n where n is 1 to 3, —

C(O)—

, —

S(O)₂—

, —

O—

, or —

(CH₂)_n—

N(R¹)—

where n is 0 to 2.

20. A compound according to any one of the proceeding claims, provided that:

when Ring C is pyridine-diyl;

Ring A is piperidin-2,4-diyl;

X1 is a bond;

Y is substituted phenyl;

X₆ is —

O—

;

Ring B is piperidin-1,4-diyl or cyclohexane-diyl; and

X₈ is —

N(R¹)(CH₂)_n—

where n is 0 to 2, then

Z is not substituted phenyl;

or

when Ring C is pyridine-diyl;

Ring A is piperidin-2,4-diyl;

X₁ is a bond;

Y is phenyl substituted with haloalkyl or pyridyl substituted with haloalkyl;

X6 is —

O—

;

Ring B is piperidin-1,4-diyl or cyclohexylene; and

X₈ is —

N(R¹)(CH₂)_n—

where n is 0 to 2, then

Z is not phenyl substituted with haloalkyl and nitro groups.