N-(1-arylpyrazol-4L)sulfonamides and their use as parasiticides

• US 7,803,832 B2
• Filed: 12/01/2009
• Issued: 09/28/2010
• Est. Priority Date: 03/18/2004
• Status: Expired due to Fees

• Current Assignee: ZOETIS LLC (Zoetis Incorporated)
• Original Assignee: Pfizer Inc., Pfizer Products Incorporated (Pfizer Inc.)
• Inventors: Critcher, Douglas James, Walshe, Nigel Derek Arthur, Lauret, Christelle
• Primary Examiner(s): Saeed; Kamal A
• Assistant Examiner(s): Rodriguez-Garcia; Valerie
• Application Number:
  US12/628,691
• Publication Number:
  US 20100075956A1
• Time in Patent Office: 301 Days
• Field of Search: 514/407, 548/372.1
• US Class Current: 514/407
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: C07D 231/40 Acylated on said nitrogen atom
• CPC Class Codes: C07D 231/42 Benzene-sulfonamido pyrazoles
• CPC Class Codes: C07D 231/50 Acylated on said nitrogen atom
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention relates to a sulfonamide compound of formula (I) or a pharmaceutically, veterinarily or agriculturally acceptable salt or solvate thereof, where the groups R¹-R⁵ are described in the description, to compositions comprising such compounds, processes for their synthesis and their use as parasiticides.

Claims

1. A method of treating a parasitic infestation or infection in a non-human animal or plant comprising administration of a therapeutically effective amount of a compound of Formula 1

or a pharmaceutically, veterinarily, or agriculturally acceptable salt thereof, wherein

R¹ is phenyl optionally substituted by one or more groups independently selected from the group consisting of halo, cyano, hydroxy, C_1-6 alkyl, C_1-6 haloalkyl, C_1-6, alkoxy, C_1-6 haloalkoxy, C_1-6 alkanoyl, C_1-6 haloalkanoyl, —

S(O)_nC_1-6alkyl, —

S(O)_nC_1-6haloalkyl and pentafluorothio;

R² is cyano;

R³ is C_1-6 alkyl, C_1-6 haloalkyl, or —

(C_0-3alkylene)-phenyl;

R⁴ is hydrogen, C_1-6 alkyl, C_1-6haloalkyl, —

(C_0-3alkylene)-R⁷ or —

(C_1-3alkylene)-R⁸;

or R³ and R⁴ taken together with the nitrogen and sulphur atoms to which they are attached form a 4 to 7-membered ring;

R⁵ is hydrogen;

R⁶ is C_1-6 alkyl or haloalkyl;

R⁷ is C_3-8cycloalkyl, —

S(O)_nR⁹, phenyl, het, —

CO₂R⁶ or C(O)N(R^a)R^b;

R⁸ is hydroxy, C_1-6 alkoxy, C_1-6 haloalkoxy, cyano, —

N(R^a)R^b or —

O—

C(O)R⁶;

R⁹ is C_1-6 alkyl, C_1-6 haloalkyl, C_3-8cycloalkyl, —

N(R^a)R^b, phenyl or het;

R^a and R^b independently represent hydrogen, C_1-6 alkyl, C_1-6 haloalkyl, C_2-6 alkenyl or C_2-6 haloalkenyl, or R^a additionally is —

(C_0-3alkylene)-C_3-8 cycloalkyl, —

(C_0-3alkylene)-phenyl or —

(C_0-3alkylene)-het, or together R^a and R^b form a 4- to 7-membered ring, optionally substituted by one or more groups independently selected from the group consisting of halo, hydroxy, C_1-6 alkyl, C_1-6haloalkyl, C_1-6 alkoxy and C_1-6haloalkoxy;

n is the integer 0, 1 or 2;

where het represents a four- to seven-membered heterocyclic group, which is aromatic or non-aromatic and which contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen, sulfur and mixtures thereof;

where both phenyl and het may be optionally substituted, where the valence allows, by one or more substituents independently selected from the group consisting of halo, hydroxy, cyano, nitro, C_1-6 alkyl, C_1-6haloalkyl, C_1-6 alkenyl, C_1-6haloalkenyl, C_1-6alkoxy, C_1-6haloalkoxy, C_3-8 cycloalkyl, C_1-6 alkanoyl, C_1-6 haloalkanoyl, C_1-6 alkylcarbonyloxy, C_1-6 alkoxycarbonyl and NR^aR^b;

where C_3-8cycloalkyl may be optionally substituted by one or more groups independently selected from the group consisting of halo, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkenyl, C_1-6haloalkenyl, hydroxy, C_1-6alkoxy and C_1-6haloalkoxy; and

where any alkylene or alkenylene group may be optionally substituted by one or more halo.

2. The method of claim 1 wherein R¹ of the Formula (1) compound is a phenyl group which bears chloro substituents at the 2- and 6-positions, and a substitutent at the 4-position selected from the group consisting of trifluoromethyl, difluoromethoxy, trifluoromethoxy, trifluoromethylthio and pentafluorothio.

3. The method of claim 2 wherein R³ is C_1-6 alkyl or C_1-6 haloalkyl.

4. The method of claim 3 wherein R³ is methyl.

5. The method of claim 4 wherein R⁴ is hydrogen, methyl, ethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, methylsulfonyl, trifluoromethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, aminosulfonyl, N,N-dimethylaminosulfonyl, methylsulfonymethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 1-(trifluoromethyl)cyclopropylmethyl, cyanomethyl, methoxycarbonyl, triazolylethyl, pyrimidin-4-ylmethyl, 1,2,4-oxadiazol-3-ylmethyl, pyrazol-3-ylmethyl, 1-methyl-1H-imidazol-2-yl, 5-methyl-isoaxazol-3-ylmethyl, 2-pyridin-4-ylethyl, aminocarbonylmethyl, benzyl or 4-fluorobenzyl.

6. The method of claim 1 wherein the Formula (1) compound is selected from the group consisting of

N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-1,1,1-trifluoro-N-methylmethanesulfonamide;

N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N-(methylsulfonyl)methanesulfonamide;

N-{3-cyano-1-[2,6-dichloro-4-pentafluorothiophenyl]-1H-pyrazol-4-yl}-N-(methylsulfonyl)methanesulfonamide;

N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}methanesulfonamide; and

N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}-N-(2,2,2-trifluoroethyl)methanesulfonamide;

or a pharmaceutically, veterinarily, or agriculturally acceptable salt thereof.

7. The method of claim 1, wherein the non-human animal is livestock or companion animals.

8. The method of claim 7 wherein livestock is sheep, pigs, or cattle.

9. The method of claim 7 wherein the companion animal is a cat, dog, or horse.

10. The method of claim 1, wherein the parasitic infestation or infection in a non-human animal or plant is caused from arthropods, arachnids, nematodes, or helminthes.

11. The method of claim 1, wherein the compound of Formula (1) is administered orally, topically, or parenterally to the non-human animal.

12. The method of claim 1, wherein the parasitic infestation or infection is in a plant.

13. The method of claim 1, further comprising one or more biologically active compounds selected from the group consisting of insecticides, acaricides, anthelmintics, fungicides, nematocides, antiprotozoals, bactericides, growth regulators, entopathogenic bacteria, viruses, and fungi.