COMBINATION

US 20070149464A1
Filed: 12/14/2006
Published: 06/28/2007
Est. Priority Date: 06/15/2005
Status: Abandoned Application

First Claim

Patent Images

1. A method of treating a parasitic infestation in a host animal, comprising simultaneously, sequentially or separately administering to said host animal:

a) a therapeutically effective amount of a compound according to formula (I) wherein;

X is selected from CR¹⁰or N;

R¹is selected from halo, cyano, hydroxy, C_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, C_1-6haloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, het, phenyl, SF₅and S(O)_nR¹¹;

R²is selected from cyano, hydroxy, C(O)OH, het, phenyl, S(O)_nR¹¹, C(O)NR^aR^band C(S)NR^aR^b;

or R²is selected from C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, amino, C_1-6alkyl amino, and di C_1-6alkyl amino each of which may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

R^aand R^bare independently selected from hydrogen, het, phenyl, and S(O)_nR¹¹;

or either one or both of R^aand R^bare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, and C(O)OC_1-6alkyl, each of which R^aor R^bmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

or R^aand R^btogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

or R²and R^etogether with the N atom to which R^eis attached may form a six to seven-membered saturated, partially saturated, or unsaturated heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

R³, R⁴, R⁵and R⁶are independently selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, phenyl, and S(O)_nR¹¹;

or either one or more of R³, R⁴, R⁵and R⁶are independently selected from C_1-4alkyl, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, amino which R³, R⁴, R⁵and R⁶may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, hydroxy, C_1-4alkyl and amino;

and where not more than two of R³, R⁴, R⁵and R⁶are selected from cyano, hydroxy, C(O)OH, nitro, phenyl, S(O)_nR¹¹, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, and amino;

R⁷is selected from halo, C_1-6alkyl and C_1-6alkoxy where, when R⁷is C_1-6alkyl or C_1-6alkoxy, R⁷may be optionally substituted with one or more halo substituents;

R⁸is selected from hydrogen, cyano, hydroxy, C(O)OH, nitro, halo, het, phenyl and S(O)_nR¹¹;

or R⁸is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, and C(O)OC_1-6alkyl, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

or R⁸is amino, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, het, phenyl and S(O)_nR¹¹;

R⁹is selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, het, phenyl, S(O)_nR¹¹and NR^eR^f;

or R⁹is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_3-8cycloalkylC_1-6alkoxy, C_1-6alkanoyl, C(O)OC_1-6alkyl, which R⁹may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

R^eand R^fare independently selected from hydrogen, het, phenyl and S(O)_nR¹¹;

or either one or both of R^eand R^fare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, —

C(O)OC_1-6alkylC_3-8cycloalkyl, —

C(O)OC_3-8cycloalkyl, each of which R^eor R^fmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

or R^eand R^ftogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;

or R^eand R²together with the atoms to which they are attached may form a six to seven-membered heterocyclic ring as previously described;

R¹⁰is selected from halo, C_1-6alkyl and C_1-6alkoxy and where when R¹⁰is C_1-6alkyl or C_1-6alkoxy it may optionally be substituted with one or more halo substituents;

each of R^cand R^dare independently selected from hydrogen, C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6haloalkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkanoyl, C_1-6haloalkanoyl, C(O)OC_1-6alkyl, het, phenyl and S(O)_nR¹¹;

or R^cand R^dtogether with the N atom to which at least one of them is attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms;

each n is independently 0, 1 or 2;

each R¹¹is independently selected from hydrogen, hydroxy, C_1-6alkyl, C_1-6haloalkyl, amino, C_1-6alkyl amino and di C_1-6alkyl amino;

each phenyl may be optionally substituted by one or more further substitutents selected from the group consisting of halo, cyano, nitro, hydroxy, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, amino, C_1-6alkyl amino, di C_1-6alkyl amino, —

NHS(O)_nR¹¹, and S(O)_nR¹¹;

and each het independently represents a four to seven membered heterocyclic ring, which is aromatic or non-aromatic, unsaturated, partially saturated or saturated and which contains one or more heteroatoms selected from nitrogen, N-oxide, oxygen, sulphur and wherein said heterocyclic ring is optionally substituted, where the valence allows, with one or more substituents selected from halo, cyano, nitro, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, OC(O) C_1-6alkyl, C_1-6alkanoyl, C(O)O C_1-6alkyl and NR^gR^h, where R^gand R^hare independently selected from hydrogen, C_1-6alkyl and C_2-6alkenyl, and where each of the above groups may include one or more optional substituents where chemically possible independently selected from cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —

C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —

C(O)OC_1-6haloalkyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, phenyl and S(O)_nR¹¹;

or a pharmaceutically acceptable salt or a prodrug thereof; and

b) a therapeutically effective amount of a second antiparasitic agent.

View all claims

1 Assignment

Timeline View

Assignment View

0 Petitions

Accused Products

Abstract

Compounds of formula (I) are used in combination with a second antiparasitic agent for the treatment of parasitic infestations in a host animal. embedded image

26 Citations

View as Search Results

43 Claims

1. A method of treating a parasitic infestation in a host animal, comprising simultaneously, sequentially or separately administering to said host animal:
- a) a therapeutically effective amount of a compound according to formula (I) wherein;
  
  X is selected from CR¹⁰or N;
  
  R¹is selected from halo, cyano, hydroxy, C_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, C_1-6haloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, het, phenyl, SF₅and S(O)_nR¹¹;
  
  R²is selected from cyano, hydroxy, C(O)OH, het, phenyl, S(O)_nR¹¹, C(O)NR^aR^band C(S)NR^aR^b;
  
  or R²is selected from C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, amino, C_1-6alkyl amino, and di C_1-6alkyl amino each of which may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R^aand R^bare independently selected from hydrogen, het, phenyl, and S(O)_nR¹¹;
  
  or either one or both of R^aand R^bare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, and C(O)OC_1-6alkyl, each of which R^aor R^bmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^aand R^btogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R²and R^etogether with the N atom to which R^eis attached may form a six to seven-membered saturated, partially saturated, or unsaturated heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R³, R⁴, R⁵and R⁶are independently selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, phenyl, and S(O)_nR¹¹;
  
  or either one or more of R³, R⁴, R⁵and R⁶are independently selected from C_1-4alkyl, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, amino which R³, R⁴, R⁵and R⁶may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, hydroxy, C_1-4alkyl and amino;
  
  and where not more than two of R³, R⁴, R⁵and R⁶are selected from cyano, hydroxy, C(O)OH, nitro, phenyl, S(O)_nR¹¹, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, and amino;
  
  R⁷is selected from halo, C_1-6alkyl and C_1-6alkoxy where, when R⁷is C_1-6alkyl or C_1-6alkoxy, R⁷may be optionally substituted with one or more halo substituents;
  
  R⁸is selected from hydrogen, cyano, hydroxy, C(O)OH, nitro, halo, het, phenyl and S(O)_nR¹¹;
  
  or R⁸is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, and C(O)OC_1-6alkyl, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R⁸is amino, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, het, phenyl and S(O)_nR¹¹;
  
  R⁹is selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, het, phenyl, S(O)_nR¹¹and NR^eR^f;
  
  or R⁹is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_3-8cycloalkylC_1-6alkoxy, C_1-6alkanoyl, C(O)OC_1-6alkyl, which R⁹may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R^eand R^fare independently selected from hydrogen, het, phenyl and S(O)_nR¹¹;
  
  or either one or both of R^eand R^fare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, —
  
  C(O)OC_1-6alkylC_3-8cycloalkyl, —
  
  C(O)OC_3-8cycloalkyl, each of which R^eor R^fmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^eand R^ftogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^eand R²together with the atoms to which they are attached may form a six to seven-membered heterocyclic ring as previously described;
  
  R¹⁰is selected from halo, C_1-6alkyl and C_1-6alkoxy and where when R¹⁰is C_1-6alkyl or C_1-6alkoxy it may optionally be substituted with one or more halo substituents;
  
  each of R^cand R^dare independently selected from hydrogen, C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6haloalkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkanoyl, C_1-6haloalkanoyl, C(O)OC_1-6alkyl, het, phenyl and S(O)_nR¹¹;
  
  or R^cand R^dtogether with the N atom to which at least one of them is attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms;
  
  each n is independently 0, 1 or 2;
  
  each R¹¹is independently selected from hydrogen, hydroxy, C_1-6alkyl, C_1-6haloalkyl, amino, C_1-6alkyl amino and di C_1-6alkyl amino;
  
  each phenyl may be optionally substituted by one or more further substitutents selected from the group consisting of halo, cyano, nitro, hydroxy, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, amino, C_1-6alkyl amino, di C_1-6alkyl amino, —
  
  NHS(O)_nR¹¹, and S(O)_nR¹¹;
  
  and each het independently represents a four to seven membered heterocyclic ring, which is aromatic or non-aromatic, unsaturated, partially saturated or saturated and which contains one or more heteroatoms selected from nitrogen, N-oxide, oxygen, sulphur and wherein said heterocyclic ring is optionally substituted, where the valence allows, with one or more substituents selected from halo, cyano, nitro, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, OC(O) C_1-6alkyl, C_1-6alkanoyl, C(O)O C_1-6alkyl and NR^gR^h, where R^gand R^hare independently selected from hydrogen, C_1-6alkyl and C_2-6alkenyl, and where each of the above groups may include one or more optional substituents where chemically possible independently selected from cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, phenyl and S(O)_nR¹¹;
  
  or a pharmaceutically acceptable salt or a prodrug thereof; and
  
  b) a therapeutically effective amount of a second antiparasitic agent.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
- - 2. The method according to claim 1 wherein the second antiparasitic agent is an anthelmintic agent.
  - 3. The method according to claim 2 wherein the anthelmintic agent is a macrocyclic lactone.
  - 4. The method according to claim 3 wherein the macrocyclic lactone anthelmintic agent is a milbemycin or a derivative thereof.
  - 5. The method according to claim 4 wherein the milbemycin or derivative thereof is milbemycin oxime.
  - 6. The method according to claim 1 wherein the compound according to formula (I) is selected from:
    - cyclopropylmethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;
      
      1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-cyclopropanecarboxamide;
      
      1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-[(2-fluoroethyl)amino]-1H-pyrazol-4-yl}cyclopropanecarboxamide;
      
      1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-dichlorocyclopropanecarboxamide;
      
      isopropyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate;
      
      1-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylamino)-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;
      
      1-{5-amino-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-2,2-difluorocyclopropanecarboxamide;
      
      1-[3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-5-(methylamino)-1H-pyrazol-4-yl]cyclopropanecarboxamide; and
      
      ethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate.
  - 7. The method according to claim 6 wherein the second antiparasitic agent is an anthelmintic agent.
  - 8. The method according to claim 7 wherein the anthelmintic agent is a macrocyclic lactone.
  - 9. The method according to claim 8 wherein the macrocyclic lactone anthelmintic agent is a milbemycin or a derivative thereof.
  - 10. The method according to claim 9 wherein the milbemycin or derivative thereof is milbemycin oxime.
  - 11. The method according to claim 1 wherein the compound according to formula (I) is cyclopropylmethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothio-phenyl]-1H-pyrazol-5-yl}carbamate.
  - 12. The method according to claim 11 wherein the second antiparasitic agent is an anthelmintic agent.
  - 13. The method according to claim 12 wherein the anthelmintic agent is a macrocyclic lactone.
  - 14. The method according to claim 13 wherein the macrocyclic lactone anthelmintic agent is a milbemycin or a derivative thereof.
  - 15. The method according to claim 14 wherein the milbemycin or derivative thereof is milbemycin oxime.
  - 16. The method according to any one of claims 1 to 15 wherein the host animal is a mammal.
  - 17. The method according to claim 16 wherein the host animal is a human.
  - 18. The method according to claim 16 wherein the host animal is a non-human mammal.
  - 19. The method according to claim 18 wherein the non-human mammal is selected from dogs, cats, horses, cattle, sheep and pigs.
  - 20. The method according to any one of claims 1 to 15 wherein the host animal is a bird or a fish.
  - 21. The method according to any one of claims 1 to 15 wherein the compound of formula (I), or pharmaceutically acceptable salt or a prodrug thereof, and the second antiparasitic agent, are administered together in a single pharmaceutical composition.
  - 22. The method according to claim 21 wherein the single pharmaceutical composition is adapted for oral administration.

23. A pharmaceutical composition comprising:
- a) a compound according to formula (I) wherein;
  
  X is selected from CR¹⁰or N;
  
  R¹is selected from halo, cyano, hydroxy, C_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, C_1-6haloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, het, phenyl, SF₅and S(O)_nR¹¹;
  
  R²is selected from cyano, hydroxy, C(O)OH, het, phenyl, S(O)_nR¹¹, C(O)NR^aR^band C(S)NR^aR^b;
  
  or R²is selected from C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, amino, C_1-6alkyl amino, and di C_1-6alkyl amino each of which may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R^aand R^bare independently selected from hydrogen, het, phenyl, and S(O)_nR¹¹;
  
  or either one or both of R^aand R^bare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, and C(O)OC_1-6alkyl, each of which R^aor R^bmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^aand R^btogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R²and R^etogether with the N atom to which R^eis attached may form a six to seven-membered saturated, partially saturated, or unsaturated heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R³, R⁴, R⁵and R⁶are independently selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, phenyl, and S(O)_nR¹¹;
  
  or either one or more of R³, R⁴, R⁵and R⁶are independently selected from C_1-4alkyl, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, amino which R³, R⁴, R⁵and R⁶may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, hydroxy, C_1-4alkyl and amino;
  
  and where not more than two of R³, R⁴, R⁵and R⁶are selected from cyano, hydroxy, C(O)OH, nitro, phenyl, S(O)_nR¹¹, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, and amino;
  
  R⁷is selected from halo, C_1-6alkyl and C_1-6alkoxy where, when R⁷is C_1-6alkyl or C_1-6alkoxy, R⁷may be optionally substituted with one or more halo substituents;
  
  R⁸is selected from hydrogen, cyano, hydroxy, C(O)OH, nitro, halo, het, phenyl and S(O)_nR¹¹;
  
  or R⁸is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, and C(O)OC_1-6alkyl, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R⁸is amino, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, het, phenyl and S(O)_nR¹¹;
  
  R⁹is selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, het, phenyl, S(O)_nR¹¹and NR^eR^f;
  
  or R⁹is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_3-8cycloalkylC_1-6alkoxy, C_1-6alkanoyl, C(O)OC_1-6alkyl, which R⁹may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R^eand R^fare independently selected from hydrogen, het, phenyl and S(O)_nR¹¹;
  
  or either one or both of R^eand R^fare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, —
  
  C(O)OC_1-6alkylC_3-8cycloalkyl, —
  
  C(O)OC_3-8cycloalkyl, each of which R^eor R^fmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^eand R^ftogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^eand R²together with the atoms to which they are attached may form a six to seven-membered heterocyclic ring as previously described;
  
  R¹⁰is selected from halo, C_1-6alkyl and C_1-6alkoxy and where when R¹⁰is C_1-6alkyl or C_1-6alkoxy it may optionally be substituted with one or more halo substituents;
  
  each of R^cand R^dare independently selected from hydrogen, C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6haloalkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkanoyl, C_1-6haloalkanoyl, C(O)OC_1-6alkyl, het, phenyl and S(O)_nR¹¹;
  
  or R^cand R^dtogether with the N atom to which at least one of them is attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms;
  
  each n is independently 0, 1 or 2;
  
  each R¹¹is independently selected from hydrogen, hydroxy, C_1-6alkyl, C_1-6haloalkyl, amino, C_1-6alkyl amino and di C_1-6alkyl amino;
  
  each phenyl may be optionally substituted by one or more further substitutents selected from the group consisting of halo, cyano, nitro, hydroxy, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, amino, C_1-6alkyl amino, di C_1-6alkyl amino, —
  
  NHS(O)_nR¹¹, and S(O)_nR¹¹;
  
  and each het independently represents a four to seven membered heterocyclic ring, which is aromatic or non-aromatic, unsaturated, partially saturated or saturated and which contains one or more heteroatoms selected from nitrogen, N-oxide, oxygen, sulphur and wherein said heterocyclic ring is optionally substituted, where the valence allows, with one or more substituents selected from halo, cyano, nitro, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, OC(O) C_1-6alkyl, C_1-6alkanoyl, C(O)O C_1-6alkyl and NR^gR^h, where R^gand R^hare independently selected from hydrogen, C_1-6alkyl and C_2-6alkenyl, and where each of the above groups may include one or more optional substituents where chemically possible independently selected from cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, phenyl and S(O)_nR¹¹;
  
  or a pharmaceutically acceptable salt or a prodrug thereof; and
  
  b) a second antiparasitic agent.
- View Dependent Claims (24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
- - 24. The pharmaceutical composition according to claim 23 wherein the second antiparasitic agent is an anthelmintic agent.
  - 25. The pharmaceutical composition according to claim 24 wherein the anthelmintic agent is a macrocyclic lactone.
  - 26. The pharmaceutical composition according to claim 25 wherein the macrocyclic lactone is a milbemycin or a derivative thereof.
  - 27. The pharmaceutical composition according to claim 26 wherein the milbemycin or derivative thereof is milbemycin oxime.
  - 28. The pharmaceutical composition according to claim 23 wherein the compound according to formula (i) is cyclopropylmethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-5-yl}carbamate.
  - 29. The pharmaceutical composition according to claim 28 wherein the second antiparasitic agent is an anthelmintic agent.
  - 30. The pharmaceutical composition according to claim 29 wherein the anthelmintic agent is a macrocyclic lactone.
  - 31. The pharmaceutical composition according to claim 30 wherein the macrocyclic lactone is a milbemycin or a derivative thereof.
  - 32. The pharmaceutical composition according to claim 31 wherein the milbemycin or derivative thereof is milbemycin oxime.
  - 33. The pharmaceutical composition according to any one of claims 23 to 32 which is adapted for oral administration.

34. A kit for treating a parasitic infestation in a host animal, comprising:
- a) a pharmaceutical composition comprising a therapeutically effective amount of a compound according to formula (I) wherein;
  
  X is selected from CR¹⁰or N;
  
  R¹is selected from halo, cyano, hydroxy, C_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, C_1-6haloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, het, phenyl, SF₅and S(O)_nR¹¹;
  
  R²is selected from cyano, hydroxy, C(O)OH, het, phenyl, S(O)_nR¹¹, C(O)NR^aR^band C(S)NR^aR^b;
  
  or R²is selected from C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, amino, C_1-6alkyl amino, and di C_1-6alkyl amino each of which may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R^aand R^bare independently selected from hydrogen, het, phenyl, and S(O)_nR¹¹;
  
  or either one or both of R^aand R^bare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, and C(O)OC_1-6alkyl, each of which R^aor R^bmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^aand R^btogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R²and R^etogether with the N atom to which R^eis attached may form a six to seven-membered saturated, partially saturated, or unsaturated heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R³, R⁴, R⁵and R⁶are independently selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, phenyl, and S(O)_nR¹¹;
  
  or either one or more of R³, R⁴, R⁵and R⁶are independently selected from C_1-4alkyl, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, amino which R³, R⁴, R⁵and R⁶may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, hydroxy, C_1-4alkyl and amino;
  
  and where not more than two of R³, R⁴, R⁵and R⁶are selected from cyano, hydroxy, C(O)OH, nitro, phenyl, S(O)_nR¹¹, C(O)NR^cR^d, C(S)NR^cR^d, C_1-4alkoxy, C_1-4alkanoyl, C(O)OC_1-4alkyl, and amino;
  
  R⁷is selected from halo, C_1-6alkyl and C_1-6alkoxy where, when R⁷is C_1-6alkyl or C_1-6alkoxy, R⁷may be optionally substituted with one or more halo substituents;
  
  R⁸is selected from hydrogen, cyano, hydroxy, C(O)OH, nitro, halo, het, phenyl and S(O)_nR¹¹;
  
  or R⁸is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_1-6alkanoyl, and C(O)OC_1-6alkyl, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R⁸is amino, which R⁸may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, het, phenyl and S(O)_nR¹¹;
  
  R⁹is selected from hydrogen, halo, cyano, hydroxy, C(O)OH, nitro, het, phenyl, S(O)_nR¹¹and NR^eR^f;
  
  or R⁹is selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkoxy, C_3-8cycloalkylC_1-6alkoxy, C_1-6alkanoyl, C(O)OC_1-6alkyl, which R⁹may be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  R^eand R^fare independently selected from hydrogen, het, phenyl and S(O)_nR¹¹;
  
  or either one or both of R^eand R^fare independently selected from C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6alkanoyl, C(O)OC_1-6alkyl, —
  
  C(O)OC_1-6alkylC_3-8cycloalkyl, —
  
  C(O)OC_3-8cycloalkyl, each of which R^eor R^fmay be optionally and independently further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^eand R^ftogether with the N atom to which they are attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms and which may be optionally further substituted by one or more substituents selected from, where chemically possible, cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, NR^cR^d, het, phenyl and S(O)_nR¹¹;
  
  or R^eand R²together with the atoms to which they are attached may form a six to seven-membered heterocyclic ring as previously described;
  
  R¹⁰is selected from halo, C_1-6alkyl and C_1-6alkoxy and where when R¹⁰is C_1-6alkyl or C_1-6alkoxy it may optionally be substituted with one or more halo substituents;
  
  each of R^cand R^dare independently selected from hydrogen, C_1-6alkyl, C_2-6alkenyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_1-6haloalkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkanoyl, C_1-6haloalkanoyl, C(O)OC_1-6alkyl, het, phenyl and S(O)_nR¹¹;
  
  or R^cand R^dtogether with the N atom to which at least one of them is attached may form a three to seven-membered saturated, partially saturated, unsaturated or aromatic heterocyclic ring which may optionally contain one or more further N, O or S atoms;
  
  each n is independently 0, 1 or 2;
  
  each R¹¹is independently selected from hydrogen, hydroxy, C_1-6alkyl, C_1-6haloalkyl, amino, C_1-6alkyl amino and di C_1-6alkyl amino;
  
  each phenyl may be optionally substituted by one or more further substitutents selected from the group consisting of halo, cyano, nitro, hydroxy, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, amino, C_1-6alkyl amino, di C_1-6alkyl amino, —
  
  NHS(O)_nR¹¹, and S(O)_nR¹¹;
  
  and each het independently represents a four to seven membered heterocyclic ring, which is aromatic or non-aromatic, unsaturated, partially saturated or saturated and which contains one or more heteroatoms selected from nitrogen, N-oxide, oxygen, sulphur and wherein said heterocyclic ring is optionally substituted, where the valence allows, with one or more substituents selected from halo, cyano, nitro, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, OC(O) C_1-6alkyl, C_1-6alkanoyl, C(O)O C_1-6alkyl and NR^gR^h, where R^gand R^hare independently selected from hydrogen, C_1-6alkyl and C_2-6alkenyl, and where each of the above groups may include one or more optional substituents where chemically possible independently selected from cyano, nitro, halo, oxo, hydroxy, C(O)OH, C(O)NR^cR^d, NR^cC(O)R^d, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-8cycloalkyl, C_3-8cycloalkylC_1-6alkyl, C_3-8cycloalkylC_1-6haloalkyl, C_1-6alkoxy, C_1-6alkanoyl, —
  
  C(O)OC_1-6alkyl, C_1-6haloalkyl, C_3-8halocycloalkyl, C_1-6haloalkoxy, C_1-6haloalkanoyl, —
  
  C(O)OC_1-6haloalkyl, amino, C_1-6alkyl amino, di C_1-6alkyl amino, phenyl and S(O)_nR¹¹;
  
  or a pharmaceutically acceptable salt or a prodrug thereof; and
  
  b) a pharmaceutical composition comprising a therapeutically effective amount of a second antiparasitic agent.
- View Dependent Claims (35, 36, 37, 38, 39, 40, 41, 42, 43)
- - 35. The kit according to claim 34 wherein the second antiparasitic agent is an anthelmintic agent.
  - 36. The kit according to claim 35 wherein the anthelmintic agent is a macrocyclic lactone.
  - 37. The kit according to claim 36 wherein the macrocyclic lactone is a milbemycin or a derivative thereof.
  - 38. The kit according to claim 37 wherein the milbemycin or derivative thereof is milbemycin oxime.
  - 39. The kit according to claim 34 wherein the compound according to formula (i) is cyclopropylmethyl {4-[1-(aminocarbonyl)cyclopropyl]-3-cyano-1-[2,6-dichloro-4-pentafluorothio-phenyl]-1H-pyrazol-5-yl}carbamate.
  - 40. The kit according to claim 39 wherein the second antiparasitic agent is an anthelmintic agent.
  - 41. The kit according to claim 40 wherein the anthelmintic agent is a macrocyclic lactone.
  - 42. The kit according to claim 41 wherein the macrocyclic lactone is a milbemycin or a derivative thereof.
  - 43. The kit according to claim 42 wherein the milbemycin or derivative thereof is milbemycin oxime.

Specification

Resources

Litigation Campaign Assessment

Current Assignee
Pfizer Inc., Pfizer Limited (Pfizer Inc.)
Original Assignee
Pfizer Inc.
Inventors
Billen, Denis, Boyle, Jessica, Gethin, David, Kyne, Graham, Critcher, Douglas, Hall, Kim

Application Number

US11/610,852
Publication Number

US 20070149464A1
Time in Patent Office

Days
Field of Search
US Class Current

514/28
CPC Class Codes

A01N 2300/00   Combinations or mixtures of...

A01N 43/90   having two or more relevant...

A01N 53/00   Biocides, pest repellants o...

A61K 2300/00   Mixtures or combinations of...

A61K 31/415   1,2-Diazoles

A61K 31/4152   having oxo groups directly ...

A61K 31/4439   containing a five-membered ...

A61K 31/7048   having oxygen as a ring het...

A61K 45/06   Mixtures of active ingredie...

A61P 33/00   Antiparasitic agents

A61P 33/02   Antiprotozoals, e.g. for le...

A61P 33/10   Anthelmintics

A61P 33/14   Ectoparasiticides, e.g. sca...

C07D 231/14   with hetero atoms or with c...

C07D 231/16   Halogen atoms or nitro radi...

C07D 231/38   Nitrogen atoms nitro radica...

C07D 401/04   directly linked by a ring-m...

COMBINATION

First Claim

1 Assignment

0 Petitions

Accused Products

Abstract

26 Citations

43 Claims

Specification

Solutions

Use Cases

Quick Links

COMBINATION

First Claim

1 Assignment

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

26 Citations

43 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links