NZ744117B2 - Novel sulfonylaminobenzamide compounds as anthelmintics - Google Patents
Novel sulfonylaminobenzamide compounds as anthelmintics Download PDFInfo
- Publication number
- NZ744117B2 NZ744117B2 NZ744117A NZ74411715A NZ744117B2 NZ 744117 B2 NZ744117 B2 NZ 744117B2 NZ 744117 A NZ744117 A NZ 744117A NZ 74411715 A NZ74411715 A NZ 74411715A NZ 744117 B2 NZ744117 B2 NZ 744117B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- substituted
- halogen
- unsubstituted
- haloalkyl
- Prior art date
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- CAWFFBLMSQUZPF-UHFFFAOYSA-N 2-(sulfonylamino)benzamide Chemical class NC(=O)C1=CC=CC=C1N=S(=O)=O CAWFFBLMSQUZPF-UHFFFAOYSA-N 0.000 title description 4
- 230000000507 anthelmentic Effects 0.000 title description 4
- 229940036592 ANTHELMINTICS Drugs 0.000 title description 2
- 239000000921 anthelmintic agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000011780 sodium chloride Substances 0.000 claims abstract description 23
- 244000045947 parasites Species 0.000 claims abstract description 13
- -1 10 N Inorganic materials 0.000 claims description 214
- 229910052736 halogen Inorganic materials 0.000 claims description 103
- 150000002367 halogens Chemical class 0.000 claims description 91
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 125000005843 halogen group Chemical group 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 125000005842 heteroatoms Chemical group 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical class 0.000 claims description 16
- 229910052796 boron Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical class 0.000 claims description 14
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 7
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 6
- 125000004433 nitrogen atoms Chemical group N* 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 5
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- XCZKKZXWDBOGPA-UHFFFAOYSA-N 2-phenylbenzene-1,4-diol Chemical class OC1=CC=C(O)C(C=2C=CC=CC=2)=C1 XCZKKZXWDBOGPA-UHFFFAOYSA-N 0.000 claims description 2
- 239000002270 dispersing agent Substances 0.000 claims description 2
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- 244000079386 endoparasites Species 0.000 abstract description 6
- 241000251539 Vertebrata <Metazoa> Species 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 76
- 150000003254 radicals Chemical class 0.000 description 45
- 239000000843 powder Substances 0.000 description 39
- 125000001309 chloro group Chemical group Cl* 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 19
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 239000000126 substance Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 201000009910 diseases by infectious agent Diseases 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- DSSYKIVIOFKYAU-OIBJUYFYSA-N (S)-camphor Chemical compound C1C[C@]2(C)C(=O)C[C@H]1C2(C)C DSSYKIVIOFKYAU-OIBJUYFYSA-N 0.000 description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N Methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N Thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 241000607479 Yersinia pestis Species 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 241000243988 Dirofilaria immitis Species 0.000 description 5
- 229940099686 Dirofilaria immitis Drugs 0.000 description 5
- 241000282326 Felis catus Species 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000244206 Nematoda Species 0.000 description 5
- 230000001058 adult Effects 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
- 125000004995 haloalkylthio group Chemical group 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 230000003071 parasitic Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000002194 synthesizing Effects 0.000 description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 4
- KEFBAMRFXYKOBI-UHFFFAOYSA-N 1,4$l^{2}-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CC[N]CC1 KEFBAMRFXYKOBI-UHFFFAOYSA-N 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000006414 CCl Chemical group ClC* 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000010192 crystallographic characterization Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 125000004438 haloalkoxy group Chemical group 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229940075963 (-)- camphor Drugs 0.000 description 3
- 229930007886 (R)-camphor Natural products 0.000 description 3
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 241000242711 Fasciola hepatica Species 0.000 description 3
- 210000004072 Lung Anatomy 0.000 description 3
- 241000242541 Trematoda Species 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000240 adjuvant Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
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- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 3
- 210000001519 tissues Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- JHPDYTWKYXLERH-UHFFFAOYSA-N 5-bromo-2-(methanesulfonamido)benzoic acid Chemical compound CS(=O)(=O)NC1=CC=C(Br)C=C1C(O)=O JHPDYTWKYXLERH-UHFFFAOYSA-N 0.000 description 2
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- 241000271566 Aves Species 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N Benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
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- HJOVHMDZYOCNQW-UHFFFAOYSA-N Isophorone Chemical compound CC1=CC(=O)CC(C)(C)C1 HJOVHMDZYOCNQW-UHFFFAOYSA-N 0.000 description 2
- 241001626440 Joyeuxiella Species 0.000 description 2
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- WLWGWVQVCSBLKZ-UHFFFAOYSA-N O1CCN(CC1)C=1C=CC(=C(C(=O)NC2=CC(=C(C(=C2)Cl)Cl)Cl)C=1)[N+](=O)[O-] Chemical compound O1CCN(CC1)C=1C=CC(=C(C(=O)NC2=CC(=C(C(=C2)Cl)Cl)Cl)C=1)[N+](=O)[O-] WLWGWVQVCSBLKZ-UHFFFAOYSA-N 0.000 description 2
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- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 2
- 230000000111 anti-oxidant Effects 0.000 description 2
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- 238000004587 chromatography analysis Methods 0.000 description 2
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- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- LHXDLQBQYFFVNW-UHFFFAOYSA-N 1,3,3-trimethyl-2-norbornanone Chemical compound C1CC2(C)C(=O)C(C)(C)C1C2 LHXDLQBQYFFVNW-UHFFFAOYSA-N 0.000 description 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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Abstract
The present invention relates to a new compound of formula (I), wherein the variables have the meaning as indicated in the claims; or an enantiomer or salt thereof. The compounds of formula (I) are useful in the control of parasites, in particular endoparasites, in and on vertebrates.
Description
Novel Sulfonylaminobenzamide Compounds as Anthelmintics
This application is a divisional of New Zealand patent application 728623, which is the
national phase entry in New Zealand of PCT international application
(published as ), filed 27 August 2015, all of
which are incorporated herein by reference.
The present invention relates to novel sulfonylaminobenzamide compounds and
their use in the control of endoparasites, for example heartworms, in warm-blooded
animals.
Heartworm (Dirofilaria immitis) is a parasitic roundworm that is spread from host
to host through the bites of mosquitoes. The definite host is the dog but it can also infect
cats and other warm-blooded animals. Although commonly being called “heartworm” the
adult worms actually reside in the pulmonary arterial system (lung arteries) for the most
part, and the primary effect on the health of the animal is damage to the lung vessels and
tissue. Occasionally, adult heartworms migrate to the right heart and even the great veins
in heavy infections. Heartworm infection may result in serious disease for the host.
Heartworm infections may be combatted with arsenic-based compounds; the
treatment is time-consuming, cumbersome and often only partly successful. Accordingly,
the main focus is on the prevention of heartworm infections. Heartworm prevention is
currently performed exclusively by year round periodical administration of a macrocyclic
lactone such as ivermectin, moxidectin or milbemycin oxime to the dog, cat or else warm-
blooded animal. Unfortunately, upcoming resistancy of Dirofilaria immitis against
macrocyclic lactones has been observed in certain parts of the USA. Accordingly, there is
a strong need for finding new classes of compounds which are effectively controlling
heartworm infections either by way of prophylaxis or by direct killing of the different
stages of heartworms. It is an object of the present invention to go some way towards
meeting this need and/or to at least provide the public with a useful choice. It now has
been found surprisingly that a group of novel sulfonylaminobenzamide compounds
effectively controls endoparasites including heartworms effectively on warm-blooded
animals.
SUMMARY OF THE INVENTION
In a first aspect the present invention provides a compound of formula
NR Y
NR - S(O ) - T
(I),
or a salt or an enantiomer thereof, wherein
n is 0 or 1;
A is C -C -cycloalkyl; C -C -halocycloalkyl; 5- or 6-membered heterocycloalkyl
3 6 3 6
having from 1 to 3 same or different heteroatoms selected from the group consisting of B,
N, O and S, which is further unsubstituted or substituted by halogen, C -C -alkyl or C -
1 4 1
C -alkoxy; or is cinnamyl, which is unsubstituted or substituted in the phenyl moiety by
halogen, C -C -alkyl or C -C -alkoxy; or is a heteroaromatic radical, which is further
1 4 1 4
unsubstituted or substituted by halogen, cyano, C -C -alkyl, C -C -haloalkyl, C -C -
1 4 1 4 1 4
alkoxy, C -C -haloalkoxy, C -C -alkanoyl, 5- or 6-membered heterocycloalkyl-C -C -
1 4 2 4 1 2
alkyl or unsubstituted or halogen-, C -C -alkyl- or C -C -alkoxy-substituted phenyl; or is
1 4 1 4
a hetero-bicyclic ring radical comprising a total of 8 to 10 ring members, from which 1 to
members are same or different heteroatoms selected from the group consisting of B, N,
O and S, and from which 0 to 2 members are a group –C(O)-, which bicyclic ring radical
is further unsubstituted or substituted by halogen, cyano, hydroxyl, C -C -alkyl or C -C -
1 4 1 4
haloalkyl;
R is H or –S(O )-T;
T is C -C -alkyl which is unsubstituted or substituted by halogen, trimethylsilyl,
C -C -cycloalkyl, carboxyl or C -C -alkoxycarbonyl; C -C -cycloalkyl; C -C -
3 6 1 4 3 6 6 12
bicarbocyclyl; a 5- or 6 membered heteroaromatic radical, which is further unsubstituted
or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl or C -C -alkoxy; 5-
1 4 1 4 1 4
or 6-membered heterocycloalkyl having from 1 to 3 same or different heteroatoms
selected from the group consisting of N, O, S and S(O ), which is further unsubstituted or
substituted by C -C -alkyl, C -C -alkoxycarbonyl or benzyloxycarbonyl ; a group
1 4 1 2
CHNN R
; amino; or N-mono- or N,N-di- C -C -alkylamino;
R is C -C -alkyl, unsubstituted or halogen-, C -C -alkyl- or C -C -haloalkyl-
1 4 1 4 1 4
substituted phenyl, unsubstituted or halogen-, C -C -alkyl- or C -C -haloalkyl-substituted
1 4 1 4
pyridyl, C -C -alkoxycarbonylmethyl or morpholinyl-carbonylmethyl;
R is H or hydroxy; and
Y is
(i) phenyl or a phenylamino, which is substituted by one or more same or different
radicals selected from the group consisting of halogen; C -C -alkyl; C -C -haloalkyl; C -
1 6 1 6 3
C -cycloalkyl; C -C -halocycloalkyl; hydroxyl; C -C -alkoxy; C -C -haloalkoxy; C -C -
6 3 6 1 6 1 6 1 6
alkylthio; C -C -haloalkylthio; C -C -alkyl-sulfinyl; C -C -haloalkylsulfinyl; C -C -
1 6 1 6 1 6 1 6
alkylsulfonyl; C -C -haloalkylsulfonyl; SF ; amino; N-mono- or N,N-di-C -C -
1 6 5 1 6
alkylamino; tri-C -C -alkylsilyl; C -C -alkoxycarbonyl; aminocarbonyl; N-mono- or
1 4 1 6
N,N-di-C -C -alkylaminocarbonyl; aminosulfonyl; N-mono- or N,N-di-C -C -
1 6 1 6
alkylaminosulfonyl; N-C -C -alkylsulfonylamino; C -C -alkoxycarbonylamino; N-C -C -
1 6 1 6 1 4
alkyl-N-C -C -alkoxycarbonylamino; cyano; nitro; and halogen-, C -C -alkyl-, C -C -
1 6 1 4 1 4
haloalkyl-, C -C -alkoxy-, C -C -haloalkoxy-, amino-, cyano- or nitro-substituted C -C -
1 4 1 4 3 6
heterocyclyl; or is
(ii) 5- or 6 membered heteroaryl or heteroarylamino, which is each further
unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -
1 4 1 4 1
C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl, or phenyl or phenylsulfonyl which is
4 1 4 2 4
each unsubstituted or substituted by halogen, cyano, nitro, methyl or methoxy; or is
(iii) benzoyl or 5- or 6 membered heteroarylcarbonyl, which is each further
unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -
1 4 1 4 1
C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl or phenyl; or is
4 1 4 2 4
(iv) a C -C -bicarbocyclic radical; or is a
6 12
(v) a radical –H C-C(O)-NH-R , wherein R is C -C -haloalkyl, C -C -alkynyl or
2 1 4 2 3
cyano-C1-C4-alkyl; or
R and Y together with the N-atom to which they are attached, form a piperidinyl
or piperazinyl radical which is substituted by C -C -alkyl, C -C -alkoxy, unsubstituted or
1 4 1 4
halogen-, C -C -alkyl-, C -C -haloalkyl-, amino- and/or C -C -alkoxy-substituted phenyl
1 4 1 4 1 4
or benzoylamino, or unsubstituted or C -C -alkyl-, C -C -haloalkyl-, C -C -cycloalkyl- or
1 4 1 4 3 6
halogen-substituted pyridyl or pyrimidinyl.
In a second aspect the present invention provides a composition for the control of
parasites, which contains as an active ingredient at least one compound of formula (I)
according to the first aspect, in addition to carriers and/or dispersants.
Also described is a compound of formula
NR Y
NR - S(O ) - T
(I),
or a salt or an enantiomer thereof, wherein
n is 0 or 1;
A is C -C -alkyl; C -C -haloalkyl; C -C -cycloalkyl; C -C -halocycloalkyl; 5- or
1 6 1 6 3 6 3 6
6-membered heterocycloalkyl having from 1 to 3 same or different heteroatoms selected
from the group consisting of B, N, O and S, which is further unsubstituted or substituted
by halogen, C -C -alkyl or C -C -alkoxy ; or is phenyl which is unsubstituted or
1 4 1 4
substituted by halogen, C -C -alkyl, C -C -haloalkyl, C -C -cycloalkyl, C -C -
1 6 1 6 3 6 3 6
halocycloalkyl, C -C -alkoxy, C -C -haloalkoxy, C -C -alkylthio, C -C -haloalkylthio,
1 6 1 6 1 6 1 6
C -C -alkyl-sulfinyl, C -C -haloalkylsulfinyl, C -C -alkylsulfonyl, C -C -
1 6 1 6 1 6 1 6
haloalkylsulfonyl, SF ; amino, N-mono- or N,N-di-C -C -alkylamino, tri-C -C -
1 6 1 4
alkylsilyl, C -C -alkoxycarbonyl, aminocarbonyl, N-mono- or N,N-di-C -C -
1 6 1 6
alkylaminocarbonyl, aminosulfonyl, N-mono- or N,N-di-C -C -alkylaminosulfonyl, C -
1 6 1
C -alkoxycarbonylamino, N-C -C -alkyl-N-C -C -alkoxycarbonylamino, cyano, nitro, or
6 1 4 1 6
unsubstituted or halogen-, C -C -alkyl-, C -C -haloalkyl-, C -C -alkoxy-, C -C -
1 4 1 4 1 4 1 4
haloalkoxy-, amino-, cyano- or nitro-substituted C -C -heterocyclyl; or is cinnamyl,
which is unsubstituted or substituted in the phenyl moiety by halogen, C -C -alkyl or C -
1 4 1
C -alkoxy; or is a heteroaromatic radical, which is further unsubstituted or substituted by
halogen, cyano, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy, C -C -haloalkoxy, C -C -
1 4 1 4 1 4 1 4 2 4
alkanoyl, 5- or 6-membered heterocycloalkyl-C -C -alkyl or unsubstituted or halogen-,
C -C -alkyl- or C -C -alkoxy-substituted phenyl; or is a hetero-bicyclic ring radical
1 4 1 4
comprising a total of 8 to 10 ring members, from which 1 to 5, preferably 1 or 2,
members are same or different heteroatoms selected from the group consisting of B, N, O
and S, and from which 0 to 2 members are a group –C(O)-, which bicyclic ring radical is
further unsubstituted or substituted by halogen, cyano, hydroxyl, C -C -alkyl or C -C -
1 4 1 4
haloalkyl;
R is H or –S(O )-T;
T is C -C -alkyl, which is unsubstituted or substituted by halogen, trimethylsilyl,
C -C -cycloalkyl, carboxyl or C -C -alkoxycarbonyl; C -C -cycloalkyl; C -C -
3 6 1 4 3 6 6 12
bicarbocyclyl ; phenyl which is unsubstituted or substituted by halogen, cyano, nitro, C -
C -alkyl, C -C -haloalkyl or C -C -alkoxy; a 5- or 6 membered heteroaromatic radical,
4 1 4 1 4
which is further unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -
1 4 1 4
haloalkyl or C -C -alkoxy; 5- or 6-membered heterocycloalkyl having from 1 to 3 same
or different heteroatoms selected from the group consisting of N, O, S and S(O ), which is
further unsubstituted or substituted by C -C -alkyl, C -C -alkoxycarbonyl or
1 4 1 2
CHNN R
benzyloxycarbonyl ; a group ; amino; or N-mono- or N,N-di- C -
C -alkylamino;
R is C -C -alkyl, unsubstituted or halogen-, C -C -alkyl- or C -C -haloalkyl-
1 4 1 4 1 4
substituted phenyl, unsubstituted or halogen-, C -C -alkyl- or C -C -haloalkyl-substituted
1 4 1 4
pyridyl, C -C -alkoxycarbonylmethyl or morpholinyl-carbonylmethyl;
R is H or hydroxy; and
Y is
(i) phenyl or a phenylamino, which is substituted by one or more same or different
radicals selected from the group consisting of halogen; C -C -alkyl; C -C -haloalkyl; C -
1 6 1 6 3
C6-cycloalkyl; C3-C6-halocycloalkyl; hydroxyl; C1-C6-alkoxy; C1-C6-haloalkoxy; C1-C6-
alkylthio; C -C -haloalkylthio; C -C -alkyl-sulfinyl; C -C -haloalkylsulfinyl; C -C -
1 6 1 6 1 6 1 6
alkylsulfonyl; C -C -haloalkylsulfonyl; SF ; amino; N-mono- or N,N-di-C -C -
1 6 5 1 6
alkylamino; tri-C -C -alkylsilyl; C -C -alkoxycarbonyl; aminocarbonyl; N-mono- or
1 4 1 6
N,N-di-C -C -alkylaminocarbonyl; aminosulfonyl; N-mono- or N,N-di-C -C -
1 6 1 6
alkylaminosulfonyl; N-C -C -alkylsulfonylamino; C -C -alkoxycarbonylamino; N-C -C -
1 6 1 6 1 4
alkyl-N-C -C -alkoxycarbonylamino; cyano; nitro; and unsubstituted or halogen-, C -C -
1 6 1 4
alkyl-, C -C -haloalkyl-, C -C -alkoxy-, C -C -haloalkoxy-, amino-, cyano- or nitro-
1 4 1 4 1 4
substituted C -C -heterocyclyl; or is
(ii) 5- or 6 membered heteroaryl or heteroarylamino, which is each further
unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -
1 4 1 4 1
C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl, or phenyl or phenylsulfonyl which is
4 1 4 2 4
each unsubstituted or substituted by halogen, cyano, nitro methyl or methoxy; or is
(iii) benzoyl or 5- or 6 membered heteroarylcarbonyl, which is each further
unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -
1 4 1 4 1
C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl or phenyl; or is
4 1 4 2 4
(iv) a C -C -bicarbocyclic radical; or is a
6 12
(v) a hetero-bicyclic ring radical comprising a total of 8 to 10 ring members, from
which 1 to 5, preferably 1 or 2, members are same or different heteroatoms selected from
the group consisting of B, N, O and S, and from which 0 to 2 members are a group –
C(O)-, which bicyclic ring radical is further unsubstituted or substituted by halogen,
cyano, hydroxyl, C -C -alkoxy, C -C -alkyl or C -C -haloalkyl; or is
1 4 1 4 1 4
(vi) a radical –H2C-C(O)-NH-R , wherein R is C1-C4-haloalkyl, C2-C3-alkynyl or
cyano-C -C -alkyl; or
R and Y together with the N-atom to which they are attached, form a piperidinyl
or piperazinyl radical which is substituted by C -C -alkyl, C -C -alkoxy, unsubstituted or
1 4 1 4
halogen-, C1-C4-alkyl-, C1-C4-haloalkyl-, amino- and/or C1-C4-alkoxy-substituted phenyl
or benzoylamino, or unsubstituted or C -C -alkyl-, C -C -haloalkyl-, C -C -cycloalkyl- or
1 4 1 4 3 6
halogen-substituted pyridyl or pyrimidinyl;
subject to the provisos that
(i) at least one of A and Y must not be a phenyl radical if T is CH ; and
(ii) T is C -C -alkyl which is unsubstituted or substituted as mentioned above if A
is C -C -alkyl or C -C -haloalkyl.
1 6 1 6
Also described is a composition comprising a compound of formula (I), or a salt
or enantiomer thereof, and at least one carrier, for example a surfactant, a solid diluent
and/or a liquid diluent.
Also described is a composition for controlling parasites, in particular
endoparasites, comprising a biologically effective amount of a compound of formula (I),
or a salt thereof, and at least one additional component selected from the group consisting
of a surfactant, a solid diluent and a liquid diluent, said composition optionally further
comprising a biologically effective amount of at least one additional pharmaceutically or
veterinary active compound or agent.
Also described is a method for controlling parasites comprising contacting the
parasites or their environment with a pharmaceutically or veterinary effective amount of a
compound of formula (I), an enantiomer or a salt thereof, (e.g., as a composition
described herein). Also described is such method wherein the parasites or their
environment are contacted with a composition comprising a pharmaceutically or
veterinary effective amount of a compound of formula (I), an enantiomer or a salt thereof,
and at least one additional component selected from the group consisting of a surfactant, a
solid diluent and a liquid diluent, said composition optionally further comprising a
pharmaceutically or veterinary effective amount of at least one additional
pharmaceutically or veterinary active compound or agent.
Also described is a method for protecting an animal from a parasitic pest
comprising administering to the animal a parasiticidally effective amount of a compound
of formula (I), an enantiomer or a salt thereof.
DETAILS OF THE INVENTION
In the above recitations, the term “alkyl”, used either alone or in compound words
such as “alkylthio”, “haloalkylthio”, “haloalkyl”, “N-alkylamino”, “N,N-di-alkyamino”
and the like includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-
propyl, n-, iso-, sec.- or tert.-butyl or the different pentyl or hexyl isomers.
The term “alkoxy” used either alone or in compound words such as “haloalkoxy”,
“alkoxycarbonyl” includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy
and the different butoxy, pentoxy and hexyloxy isomers. “Alkylthio” includes branched
or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different
propylthio, butylthio, pentylthio and hexylthio isomers.
“Alkylsulfinyl” includes both enantiomers of an alkylsulfinyl group. Examples of
“alkylsulfinyl” include CH S(O)-, CH CH S(O)-, CH CH CH S(O)-, (CH ) CHS(O)-
3 3 2 3 2 2 3 2
and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers.
“Alkylcarbonyl” denotes a straight-chain or branched alkyl moieties bonded to a
C(=O) moiety. Examples of “alkylcarbonyl” include CH C(=O)-, CH CH CH C(=O)-
3 3 2 2
and (CH ) CHC(=O)-. Examples of “alkoxycarbonyl” include CH OC(=O)-,
3 2 3
CH CH OC(=O), CH CH CH OC(=O)-, (CH ) CHOC(=O)- and the different butoxy- or
3 2 3 2 2 3 2
pentoxycarbonyl isomers, for example tert.-butoxycarbonyl (Boc). Examples of
“alkoxycarbonylamino” include tert.-butoxycarbonylamino, examples of “N-
alkoxycarbonyl” include N-tert.-butoxycarbonyl and examples of “N-alkylamino”
include N-methylamino. Examples of “N-mono- or N,N-di-alkylaminocarbonyl” include
N-methylaminocarbonyl, N-ethylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N,N-
di-methylaminocarbonyl or N,N-di-ethylaminocarbonyl. Examples of “alkyl-
carbonylamino” include methylcarbonylamino or ethylcarbonylamino.
Examples of "alkylsulfonyl" include CH S(O) -, CH CH S(O) -,
3 2 3 2 2
CH CH CH S(O) -, (CH ) CHS(O) -, and the different butylsulfonyl, pentylsulfonyl and
3 2 2 2 3 2 2
hexylsulfonyl isomers. Examples of “N-mono- or N,N-di-alkylaminosulfonyl” include N-
methylaminosulfonyl, N-ethylaminosulfonyl, N-methyl-N-ethylaminosulfonyl, N,N-di-
methylaminosulfonyl or N,N-di-ethylaminosulfonyl. Examples of “alkylsulfonylamino”
include methylsulfonylamino or ethylsulfonylamino.
“Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl. The term “alkylcycloalkyl” denotes alkyl substitution on a cycloalkyl moiety
and includes, for example, ethylcyclopropyl, i-propylcyclobutyl, 3-methylcyclopentyl and
4-methycyclohexyl.
Examples of C -C -bicarbocyclyl are the radical of (+)- or (-)-campher (1,7,7-
6 12
H C CH
trimethylbicyclo[2.2.1]heptanone), a radical , a radical or indanyl.
The term “halogen”, either alone or in compound words such as “haloalkyl”,
includes fluorine, chlorine, bromine or iodine. Further, when used in compound words
such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms
which may be the same or different. Examples of “haloalkyl” include F C-, ClCH -,
CF CH - and CF CCl -. The terms “halocycloalkyl”, “haloalkoxy”, “haloalkylthio”, and
3 2 3 2
the like, are defined analogously to the term “haloalkyl”. Examples of “haloalkoxy”
include CF O-, CF CF -O-, CF CH O-, CCl CH O-, CF CHFCF O- and
3 3 2 3 2 3 2 3 2
HCF CH CH O-. Examples of “haloalkylthio” include CCl S-, CF S-, CCl CH S- and
2 2 2 3 3 3 2
ClCH CH CH S-. Examples of “haloalkylsulfinyl” include CF S(O)-, CCl S(O)-,
2 2 2 3 3
CF CH S(O)- and CF CF S(O)-. Examples of “haloalkylsulfonyl” include CF S(O) -,
3 2 3 2 3 2
CCl S(O) -, CF CH S(O) - and CF CF S(O) -.
3 2 3 2 2 3 2 2
The total number of carbon atoms in a substituent group is indicated by the “C -
C ” prefix where i and j are integers. For example, C -C alkylsulfonyl designates
j 1 4
methylsulfonyl through butylsulfonyl.
When a compound is substituted with a substituent bearing a subscript that
indicates the number of said substituents can exceed 1, said substituents (when they
exceed 1) are independently selected from the group of defined substituents, e.g., (R ) , n
is 1 or 2.
“Aromatic” indicates that each of the ring atoms is essentially in the same plane
and has ap-orbital perpendicular to the ring plane, and in which (4n + 2) π electrons,
where n is a positive integer, are associated with the ring to comply with Hϋckel's rule.
The terms “heterocyclyl”, “heterocyclic ring” or “heterocycle” denote a ring in
which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen
sulfur or a group S(O) or S(O ). Typically a heterocyclic ring contains no more than 4
nitrogens, no more than 2 oxygens and no more than 2 sulfurs. In addition, the
heterocyclic ring may contain a group –C(O)-, -S(O)- or –S(O )-. Unless otherwise
indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated
ring. When a fully unsaturated heterocyclic ring satisfies Hϋckel's rule, then said ring is
also called a “heteroaromatic ring” or “heteroaryl” substituent. Unless otherwise
indicated, heterocyclic rings and ring systems can be attached through any available
carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
The term heterocyclyl, either alone or in compound words such as
heterocyclyloxy may be, for example a 5- or 6-membered heterocyclic radical having
from 1 to 4, preferably from 1 to 3 same or different heteroatoms selected from the group
consisting of B, N, O and S, which is further unsubstituted or substituted. Examples of
suitable substituents of the heterocyclyl are halogen, C -C -alkyl, C -C -haloalkyl, C -C -
1 6 1 6 3 6
cycloalkyl, C -C -halocycloalkyl, hydroxy, C -C -alkoxy, C -C -haloalkoxy, C -C -
3 6 1 6 1 6 1 6
alkylthio, C -C -haloalkylthio, C -C -alkylsulfinyl, C -C -haloalkylsulfinyl, C -C -
1 6 1 6 1 6 1 6
alkylsulfonyl, C -C -haloalkylsulfonyl, cyano, nitro, amino, N-mono- or N,N-di-C -C -
1 6 1 4
alkylamino, C -C -alkoxycarbonyl, sulfonamido, N-mono- or N,N, di-C -C -
1 6 1 4
alkylsulfonamido, C -C -alkylcarbonylamino, N-mono- or N,N-di-C -C -
1 6 1 6
alkylaminocarbonyl, C -C -alkanoyl, or phenyl, which is unsubstituted or substituted by
halogen, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy, C -C -haloalkoxy, cyano or nitro.
1 6 1 6 1 6 1 6
The term heterocyclyl may denote, for example, a 5- or 6-membered heteroaryl
radical having from 1 to 4, preferably from 1 to 3 same or different heteroatoms selected
from the group consisting of N, O and S, which is further unsubstituted or substituted by
one or more substituents as defined above for heterocyclyl. The heteroaryl radical is
preferably substituted by 0 to 3, in particular 0, 1 or 2 substituents from the group as
defined above.
The term 5- or 6-membered heteroaryl, either alone or in terms such as
heteroarylamino or heteroarylcarbonyl, may include, for example, a thienyl, pyrryl,
pyrazolyl, furyl, oxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyrimidinyl or
thiazinyl radical which is each unsubstituted or substituted, for example, by halogen,
cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -C -cycloalkyl, C -C -alkoxy, C -C -
1 2 1 2 3 6 1 4 2 4
alkanoyl, C1-C4-alkoxycarbonyl or unsubstituted or substituted phenyl.
The term heterocyclyl may further denote a 3 to 6-membered heterocycloalkyl
radical having from 1 to 3 same or different heteroatoms selected from the group
consisting of B, N, O and S, which is further unsubstituted or substituted by one or more
substituents as defined above for heterocyclyl. The heterocycloalkylene radical is
preferably substituted by 0 to 3, in particular 0, 1 or 2 substituents from the group as
defined above. Examples are tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperidinyl,
piperazinyl or dioxoborolanyl which is each unsubstituted or substituted by halogen, C -
C -alkyl, C -C -haloalkyl or C -C -alkoxy.
2 1 2 1 2
Examples of heterocyclyloxy are 2-, 3-or 4-pyridyloxy or pyrimidinyloxy,
which is each unsustituted or substituted by by halogen, C -C -alkyl, C -C -cycloalkyl,
1 2 3 6
C -C -haloalkyl or C -C -alkoxy.
1 2 1 2
Examples of heterobicyclic ring radicals are benzoxazolyl, benzothiazolyl,
tetrahydro-benzothiazolyl, indolyl, benzimidazolyl, benzopyrazolyl, 5,6-dihydro-4H-
cyclopenta[b]thiophenyl, methylenedioxoyphenyl, benzooxaboronyl, chinolinyl,
triazolopyrimidinonyl, for example 1,2,3-triazolo[4,5-d]pyrimidinoneyl, or
phthalhydrazidyl, which may each be unsubstituted or substituted, for example, by
halogen, cyano, C -C -alkyl, C -C -haloalkyl, hydroxy or C -C -alkoxy.
1 4 1 2 1 2
Concerning the variables contained in the compounds of formula (I), the following
meanings and preferences apply.
The variable n is preferably 1 if A is a phenyl radical. The variable n is preferably
0 if A is different from a phenyl radical, e.g. if A is C -C -alkyl, C -C -haloalkyl, C -C -
1 6 1 6 3 6
cycloalkyl; C -C -halocycloalkyl; a 5- or 6-membered heterocycloalkyl radical, a
heteroaromatic radical, or a hetero-bicyclic ring radical.
Preferred substituents of the phenyl radical A are halogen; C -C -alkyl; C -C -
1 4 1 4
haloalkyl; amino; C -C -alkoxy; C -C -haloalkoxy; C -C -haloalkylthio; C -C -
1 4 1 4 1 4 1 4
alkylsulfonyl; C1-C4-haloalkylsulfonyl; tri-C1-C2-alkylsilyl; C1-C4-alkoxycarbonyl; N-
mono- or N,N-di-C -C -alkylaminocarbonyl; aminosulfonyl; N-mono- or N,N-di-C -C -
1 4 1 4
alkylaminosulfonyl; N-C1-C2-alkyl-N-C1-C4-alkoxycarbonylamino; cyano; nitro; or 5- or
6-membered heterocycloalkyl comprising 1 or 2 same or different heteroatoms selected
from O, S and N, which is unsubstituted or substituted by halogen, C1-C2-alkyl, C1-C2-
haloalkyl or C -C -alkoxy.
More preferred substituents of the phenyl radical A are halogen; C -C -alkyl; C -
1 2 1
C -haloalkyl; amino; C -C -alkoxy; C -C -haloalkoxy; C -C -alkylsulfonyl; C -C -
4 1 4 1 4 1 4 1 4
haloalkylsulfonyl; trimethylsilyl; C -C -alkoxycarbonyl; N,N-di-C -C -alkylamino-
1 4 1 2
carbonyl; aminosulfonyl; N,N-di-C -C -alkylaminosulfonyl; N-C -C -alkyl-N-C -C -
1 2 1 2 1 4
alkoxycarbonylamino; cyano; nitro; or a heterocycloalkyl radical selected from the group
consisting of tetrahydrofuranyl, pyrrolidinyl, morpholinyl and piperidinyl.
Especially preferred substituents of the phenyl radical A are halogen, C -C -alkyl,
C -C -haloalkyl, C -C -alkoxy, C -C -haloalkoxy or cyano, and especially chlorine,
1 2 1 2 1 2
fluorine or CF .
Specific preferred phenyl radicals A are 2-, 3- or 4-Cl-phenyl, 4-CF -phenyl, 3,5-
di-Cl-phenyl, 3,5-di-CF -phenyl, 2,4,6-tri-Cl-phenyl, 3,4,5-tri-Cl-phenyl, 2-ClCF -
phenyl, 2-CF Cl-phenyl or 2,6-di-ClCF -phenyl, in particular 4-Cl-phenyl.
A as C -C -alkyl is preferably C -C -alkyl. A as haloalkyl is preferably C -C -
1 6 1 4 1 2
haloalkyl, in particular CF .
A as 5- or 6-membered heterocycloalkyl is preferably a pyrrolidinyl, piperazinyl,
morpholinyl or dioxaborolanyl, which is each unsubstituted or substituted by methyl.
A as a heteroaromatic radical is preferably pyrryl, pyrazolyl,triazolyl, thienyl,
thiazinyl, thiazolyl, pyridyl or pyrimidinyl , which is each unsubstituted or substituted by
halogen, cyano, C -C -alkyl, C -C -alkoxy, C -C -haloalkyl, acetyl, propionyl, phenyl or
1 2 1 2 1 2
morpholinyl-methyl. Particularly preferred meanings of A as heteroaromatic radical
are 2-, 3- or 4-pyridyl which is unsubstituted or substituted by halogen, cyano, C -C -
alkoxy, acetyl or propionyl; pyrimidinyl which is unsubstituted or substituted by halogen
or acetyl; 1,2,4-triazolyl which is unsubstituted or substituted by phenyl;, thienyl
which is unsubstituted or substituted by halogen, acetyl or morpholinyl-methyl;
pyrazolyl or yl which is each unsubstituted or substituted by methyl; or thiazinyl.
A as a hetero-bicyclic ring radical is preferably indolyl, benzopyrazolyl or
benzothiazol, which is each unsubstituted or substituted by methyl.
According to a preferred embodiment described herein A is C -C -alkyl; C -C -
1 4 1 2
haloalkyl; heterocycloalkyl selected from pyrrolidinyl, piperazinyl, morpholinyl and
dioxaborolanyl, which is each unsubstituted or substituted by methyl; a heteroaromatic
radical selected from pyrryl, pyrazolyl, triazolyl, thienyl, thiazinyl, thiazolyl, pyridyl and
pyrimidinyl, which is each unsubstituted or substituted by halogen, cyano, C -C -alkyl,
C -C -alkoxy, C -C -haloalkyl, acetyl, propionyl, phenyl or morpholinyl-methyl; or a
1 2 1 2
hetero-bicyclic ring radical selected from indolyl, benzopyrazolyl and benzothiazol,
which is each unsubstituted or substituted by methyl.
The variable R is preferably H.
T as alkyl radical is preferably C -C -alkyl, which is unsubstituted or substituted
by halogen, cyclopropyl, cyclohexyl, trimethylsilyl, carboxy or C -C -alkoxycarbonyl.
Particularly preferred meanings of T as alkyl radical are C -C -alkyl; C -C -haloalkyl, in
1 4 1 3
particular CF , -CH -CF or -CH -CH -CF ; trimethylsilyl-C -C -alkyl; C -C -
3 2 3 2 2 3 1 2 1 2
alkoxycarbonylmethyl; carboxymethyl; or cyclohexylmethyl; especially methyl.
T as C -C -cycloalkyl, in preferably cyclopropyl or cyclohexyl.
T as bicarbocyclyl is, for example, a bicycloalkylene or bicycloalkylenone radical,
for example 1,7,7-trimethylbicyclo[2.2.1]heptyl or 1,7,7-trimethylbicyclo[2.2.1]heptan
one-yl ((+)- or (-)-camphor).
T as phenyl radical is preferably phenyl which is unsubstituted or substituted by
fluorine, chlorine, methyl, methoxy, CF or nitro.
T as heteroaromatic radical is preferably pyridyl, thienyl or pyrimidinyl.
T as heterocycloalkyl is preferably piperidinyl, piperazinyl, tetrahydropyranyl,
morpholinyl, thiomorpholinyl or thiomorpholinyl-1,1-dioxide, which is each
unsubstituted or substituted by methyl or benzyloxycarbonyl. Particularly preferred
heterocyclyl radicals T are 1-methylpiperazinyl, 1-(benzyloxycarbonyl)-piperazinyl,
tetrahydro-2H-pyranyl or, thiomorpholinyl-1,1-dioxide.
R is preferably methyl, halophenyl, trifluoromethylpyridyl, tert.-
butoxycarbonylmethyl or morpholinyloxycarbonylmethyl.
T is preferably C1-C4-alkyl; C1-C3-haloalkyl; trimethylsilyl-C1-C2-alkyl; C1-C2-
alkoxycarbonylmethyl; carboxymethyl; cyclohexylmethyl; C -C -cycloalkyl; 1,7,7-
trimethylbicyclo[2.2.1]heptyl or 1,7,7-trimethylbicyclo[2.2.1]heptanone-yl ((+)- or (-)-
camphor); phenyl which is unsubstituted or substituted by fluorine, chlorine, methyl,
methoxy, CF3 or nitro; pyridyl, thienyl or pyrimidinyl; heterocycloalkyl selected from
piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl or
thiomorpholinyl-1,1-dioxide, which is each unsubstituted or substituted by methyl or
NN R
benzyloxycarbonyl; or a group wherein R is methyl, halophenyl,
trifluoromethylpyridyl, tert.-butoxycarbonylmethyl or morpholinyloxycarbonylmethyl.
R is preferably H.
Preferred substituents of the phenyl or phenylamino radical Y are halogen; C -C -
alkyl; C -C -haloalkyl; C -C -cycloalkyl; C -C -alkoxy; C -C -haloalkoxy; C -C -
1 4 3 6 1 4 1 4 1 4
haloalkylthio; SF ; N,N-di-C -C -alkylamino-C -C -alkylaminocarbonyl; N-C -C -
1 4 1 4 1 4
alkylsulfonylamino; cyano; nitro; hydroxy; B(OH) or methylsulfonylamino.
More preferred substituents of the phenyl or phenylamino radical Y are halogen;
C -C -alkyl; C -C -haloalkyl; C -C -alkoxy; C -C -haloalkoxy; C -C -haloalkylthio; SF ;
1 2 1 3 1 2 1 3 1 2 5
cyano; nitro; hydroxy; or methylsulfonylamino.
Particularly preferred substituents of the phenyl or phenylamino radical Y
halogen, methyl, C -C -haloalkyl, methoxy, C -C -haloalkoxy, SCF , SF , cyano, nitro or
1 3 1 3 3 5
hydroxy and especially halogen or CF .
A specific preferred phenyl radical Y is 3,4,5-trichlorophenyl, 3,5-di-
trifluoromethylchlorophenyl and 3,5-di-trifluoromethylphenyl.
A specific preferred phenylamino radical Y is phenyl amino which is substituted
by chlorine, bromine, methyl trifluoromethyl, methoxy, cyano or nitro.
A heteroaryl radical Y is, for example, pyrryl, pyrazolyl, oxazolyl, thienyl,
thiazolyl, isothiazolyl, thiadiazolyl, pyridyl or pyrimidinyl, which is each unsubstituted or
substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy, C -C -
1 4 1 2 1 2 1 2
alkoxycarbonyl, or phenyl or phenylsulfonyl which is in turn each unsubstituted or
substituted by halogen, cyano, nitro methyl or methoxy.
A heteroaryl radical Y is preferably 2-, 3- or 4-pyridyl which is unsubstituted or
substituted by halogen, C1-C4-alkyl or C1-C2-alkoxy; 2-thienyl, which is unsubstituted or
substituted by C -C -alkyl or C -C -alkoxycarbonyl; 2-thiazolyl, which is unsubstituted or
1 2 1 2
substituted by halogen, cyano, nitro, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxycarbonyl,
or phenyl or phenylsulfonyl which is in turn each unsubstituted opr substituted by
halogen, cyano, nitro or methyl; 5-isothiazoyl which is unsubstituted or substituted by
halogen or methyl; 2-oxazolyl, which is unsubstituted or substituted by C -C -alkyl or C -
1 2 1
C -haloalkyl; or 1,3,4-thiadiazolyl, which is unsubstituted or substituted by C -C -
2 1 2
alkyl or C -C -haloalkyl.
A heteroarylamino radical Y is preferably 2-, 3- or 4-pyridylamino, which is
unsubstituted or substituted by halogen, C -C -alkyl or C -C -alkoxy.
1 4 1 2
A benzoyl or heteroarylcarbonyl radical Y is preferably benzoyl, which is
unsubstituted or substituted by halogen; or 2-, 3- or 4-pyridylcarbonyl which is
unsubstituted or substituted by halogen or C -C -alkyl.
A preferred bicarbocyclic radical Y is preferably a radical , a radical
H C CH
or indanyl.
A preferred heterobicyclic ring radical Y is benzothiazolyl, indolyl, chinolinyl,
methylenedioxophenyl, benzooxaboronyl, triazolopyrimidinonyl or phthalhydrazidyl,
which is each be unsubstituted or substituted by halogen, C -C -alkyl, C -C -haloalkyl,
1 4 1 2
C -C -alkoxy or hydroxy.
The variable R is preferably propynyl, 2,2,2-trifluoroethyl or cyanomethyl.
A preferred radical Y is thus (i) phenyl or phenylamino which is substituted by
halogen, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy, C -C -haloalkoxy, C -C -
1 2 1 3 1 2 1 3 1 2
haloalkylthio, SF , cyano, nitro, hydroxy or methylsulfonylamino; (iia) heteroaryl
selected from 2-, 3- or 4-pyridyl which is unsubstituted or substituted by halogen, C -C -
alkyl or C -C -alkoxy, 2-thienyl, which is unsubstituted or substituted by C -C -alkyl or
1 2 1 2
C -C -alkoxycarbonyl, 2-thiazolyl, which is unsubstituted or substituted by halogen,
cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -C -alkoxycarbonyl, or phenyl or
1 2 1 2 1 2
phenylsulfonyl which is in turn each unsubstituted or substituted by halogen, cyano, nitro
or methyl, 5-isothiazoyl which is unsubstituted or substituted by halogen or methyl, 2-
oxazolyl, which is unsubstituted or substituted by C -C -alkyl or C -C -haloalkyl, or
1 2 1 2
1,3,4-thiadiazolyl, which is unsubstituted or substituted by C -C -alkyl or C -C -
1 2 1 2
haloalkyl; (iib) heteroarylamino selected from 2-, 3- or 4-pyridylamino, which is
unsubstituted or substituted by halogen, C -C -alkyl or C -C -alkoxy; (iii) benzoyl, which
1 4 1 2
is unsubstituted or substituted by halogen, or 2-, 3- or 4-pyridylcarbonyl which is
unsubstituted or substituted by halogen or C -C -alkyl; (iv) a bicarbocyclic radical
H C CH
selected from a radical , a radical and indanyl; (v) a heterobicyclic ring
radical selected from benzothiazolyl, indolyl, chinolinyl, methylenedioxophenyl,
benzooxaboronyl, triazolopyrimidinonyl and phthalhydrazidyl, which is each be
unsubstituted or substituted by halogen, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy or
1 4 1 2 1 4
hydroxy; or (vi) a radical –H C-C(O)-NH-R , wherein R is propynyl, 2,2,2-
trifluoroethyl or cyanomethyl.
If R and Y together with the N-atom to which they are attached, form a
piperidinyl or piperazinyl radical, said piperidinyl or piperazinyl radical is preferably
substituted by methyl; methoxy; halogen-, amino-, methoxy- or trifluoromethyl-
substituted phenyl or benzoylamino; or halogen-, trifluoromethyl- and/or cyclopropyl-
substituted pyridyl or pyrimidinyl.
One embodiment described herein concerns a compound of formula
NH-SO CH
(Ia),
wherein n has the above-given meaning including the preferences, Y’ is phenyl which is
substituted as mentioned above including the preferences; and A’ is C -C -alkyl; C -C -
1 6 1 6
haloalkyl; C -C -cycloalkyl; C -C -halocycloalkyl; 5- or 6-membered heterocycloalkyl
3 6 3 6
having from 1 to 3 same or different heteroatoms selected from the group consisting of B,
N, O and S, which is further unsubstituted or substituted by halogen, C -C -alkyl or C -
1 4 1
C -alkoxy; a heteroaromatic radical, which is further unsubstituted or substituted by
halogen, cyano, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy, C -C -haloalkoxy, C -C -
1 4 1 4 1 4 1 4 1 4
alkanoyl, 5- or 6-membered heterocycloalkyl-C -C -alkyl or unsubstituted or halogen-,
C -C -alkyl- or C -C -alkoxy-substituted phenyl; or is a hetero-bicyclic ring radical
1 4 1 4
comprising a total of 8 to 10 ring members, from which 1 to 5, preferably 1 or 2,
members are same or different heteroatoms selected from the group consisting of B, N, O
and S, and from which 0 to 2 members are a group –C(O)-, which bicyclic ring radical is
further unsubstituted or substituted by halogen, cyano, hydroxyl, C -C -alkoxy, C -C -
1 4 1 4
alkyl or C -C -haloalkyl.
A compound of formula (Ia), wherein Y’ is phenyl which is substituted by 2 or 3
same or different radicals selected from halogen or CF ; and A’ is C -C -alkyl; CF ;
3 1 4 3
pyrrolidinyl, piperazinyl, morpholinyl or dioxaborolanyl, which is each unsubstituted or
substituted by methyl; pyrryl, pyrazolyl, triazolyl, thienyl, thiazinyl, thiazolyl, pyridyl or
pyrimidinyl , which is each unsubstituted or substituted by halogen, cyano, C -C -alkyl,
C -C -alkoxy, C -C -haloalkyl, acetyl, propionyl, phenyl or morpholinyl-methyl; or
1 2 1 2
indolyl, benzopyrazolyl or benzothiazolyl, which is each unsubstituted or substituted by
methyl or methoxy; and n is 0 or 1, in particular 1; is especially preferred.
A further preferred embodiment described herein concerns a compound of
formula
NR -SO T
(Ib),
wherein A is phenyl which is unsubstituted or substituted as mentioned above including
the preferences, Y is phenyl which is substituted as mentioned above including the
preferences, T is C -C -alkyl, which is unsubstituted or substituted by halogen,
trimethylsilyl, C -C -cycloalkyl, carboxy or C -C -alkoxycarbonyl; C -C -cycloalkyl; C -
3 6 1 4 3 6 6
C -bicarbocyclyl ; phenyl which is unsubstituted or substituted by halogen, cyano, nitro,
C -C -alkyl, C -C -haloalkyl or C -C -alkoxy; a 5- or 6 membered heteroaromatic radical,
1 4 1 4 1 4
which is further unsubstituted or substituted by halogen, C -C -alkyl or C -C -alkoxy;
1 4 1 4
amino; N-mono- or N,N-di- C -C -alkylamino; 5- or 6-membered heterocycloalkyl
having from 1 to 3 same or different heteroatoms selected from the group consisting of N,
O, S and S(O ), which is further unsubstituted or substituted by C -C -alkyl; or a group
2 1 4
CHNN R
, and R is C -C -alkyl, unsubstituted or halogen-, C -C -alkyl- or
1 4 1 4
C -C -haloalkyl-substituted phenyl, unsubstituted or halogen-, C -C -alkyl- or C -C -
1 4 1 4 1 4
haloalkyl-substituted pyridyl, C -C -alkoxycarbonylmethyl or morpholinyl-
carbonylmethyl.
A preferred embodiment relates to a compound of formula (Ib), wherein A is
phenyl which is unsubstituted or preferably mono-substituted by chlorine, fluorine or
CF , Y is phenyl which is substituted by 2 or 3 same or different radicals selected from
halogen or CF , and T is C -C -alkyl, which is unsubstituted or substituted by halogen,
3 2 4
cyclopropyl, cyclohexyl, trimethylsilyl, carboxy or C -C -alkoxycarbony; cyclopropyl or
cyclohexyl; the radical of (+)- or (-)-camphor; phenyl which is unsubstituted or
substituted by fluorine, chlorine, methyl, methoxy, CF or nitro; or pyridyl, thienyl or
pyrimidinyl; piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl or
thiomorpholinyl-1,1-dioxide, which is each unsubstituted or substituted by methyl or
benzyloxycarbonyl.
A further preferred embodiment described herein concerns a compound of
formula
O Y''
NH-SO -CH
(Ic),
wherein A is phenyl which is unsubstituted or substituted as mentioned above including
the preferences, R is H or hydroxyl; and Y’’ is
(i) 5- or 6 membered heteroaryl or heteroarylamino, which is each further
unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -
1 4 1 4 1
C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl or phenyl or phenylsulfonyl which is
4 1 4 1 4
each unsubstituted or substituted by halogen, cyano, nitro methyl or methoxy; or is
(ii) benzoyl or 5- or 6 membered heteroarylcarbonyl, which is each further
unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C -
1 4 1 4 1
C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl or phenyl; or is
4 1 4 1 4
(iii) a C -C -bicarbocyclic radical; or is a
6 12
(iv) a hetero-bicyclic ring radical comprising a total of 8 to 10 ring members, from
which 1 to 5, preferably 1 or 2, are same or different heteroatoms selected from the group
consisting of B, N, O and S, and from which 0 to 2 are a group –C(O)-, which bicyclic
ring radical is further unsubstituted or substituted by halogen, cyano, hydroxyl, C -C -
alkyl, C -C -alkoxy or C -C -haloalkyl; or is
1 4 1 4
(v) a radical –H C-C(O)-NH-R , wherein R is C -C -haloalkyl, C -C -alkynyl or
2 1 4 2 3
cyano-C -C -alkyl; or R and Y together with the N-atom to which they are attached,
form a piperidinyl or piperazinyl radical which is substituted by C -C -alkyl, C -C -
1 4 1 4
alkoxy, unsubstituted or halogen-, C -C -alkyl-, halo- C -C -alkyl-, amino- and/or C -C -
1 4 1 4 1 4
alkoxy-substituted phenyl or benzoylamino, or unsubstituted or C -C -alkyl-, C -C -
1 4 1 4
haloalkyl-, C -C -cycloalkyl- or halogen-substituted pyridyl or pyrimidinyl.
Concerning a preferred embodiment of the compounds of formula (Ic), A is
phenyl which is unsubstituted or preferably mono-substituted by chlorine, fluorine or
CF ; R is H, and Y’’ is
(i) 2-, 3- or 4-pyridyl which is unsubstituted or substituted by halogen, C -C -alkyl
or C -C -alkoxy; 2-thienyl, which is unsubstituted or substituted by C -C -alkyl, C -C -
1 2 1 2 1 2
alkoxycarbonyl; 2-thiazolyl, which is unsubstituted or substituted by halogen, cyano,
nitro, C -C -alkyl, C -C -haloalkyl, C -C -alkoxycarbonyl, or phenyl or phenylsulfonyl
1 2 1 2 1 2
which is in turn each unsubstituted opr substituted by halogen, cyano, nitro or methyl; 5-
isothiazoyl which is unsubstituted or substituted by halogen or methyl; 2-oxazolyl, which
is unsubstituted or substituted by C -C -alkyl or C -C -haloalkyl; or 1,3,4-thiadiazolyl,
1 2 1 2
which is unsubstituted or substituted by C -C -alkyl or C -C -haloalkyl; 2-, 3- or 4-
1 2 1 2
pyridylamino, which is unsubstituted or substituted by halogen, C -C -alkyl or C -C -
1 4 1 2
alkoxy; or
(ii) benzoyl, which is unsubstituted or substituted by halogen or 2-, 3- or 4-
pyridylcarbonyl which is unsubstituted or substituted by halogen or C1-C4-alkyl; or
H C CH
(iii) a radical , a radical or indanyl; or
(iv) benzothiazolyl, indolyl, chinolinyl, methylenedioxophenyl, benzooxaboronyl,
triazolopyrimidinonyl or phthalhydrazidyl, which is each be unsubstituted or substituted
by halogen, C -C -alkyl, C -C -haloalkyl or hydroxy; or
1 4 1 2
(v) a radical –H2C-C(O)-NH-CH2-C≡CH, –H2C-C(O)-NH-CH2-CN or –H2C-
C(O)-NH-CH -CF or R and Y together with the N-atom to which they are attached,
2 3;
form a piperidinyl or piperazinyl radical, which is substituted by methyl; methoxy;
halogen-, amino-, methoxy- or trifluoromethyl-substituted phenyl or benzoylamino; or
halogen-, trifluoromethyl- and/or cyclopropyl-substituted pyridyl or pyrimidinyl.
A salt of a compound or formula (I) may be produced in known manner. Acid
addition salts, for example, are obtainable by treatment with a suitable acid or a suitable
ion exchange reagent, and salts with bases are obtainable by treatment with a suitable
base or a suitable ion exchange reagent.
Salts of compounds of formula (I) can be converted into the free compounds by
the usual means, acid addition salts e.g. by treating with a suitable basic composition or
with a suitable ion exchange reagent, and salts with bases e.g. by treating with a suitable
acid or a suitable ion exchange reagent.
Salts of compounds of formula (I) can be converted into other salts of compounds
of the formula (I) in a known manner; acid addition salts can be converted for example
into other acid addition salts, e.g. by treating a salt of an inorganic acid, such as a
hydrochloride, with a suitable metal salt, such as a sodium, barium, or silver salt, of an
acid, e.g. with silver acetate, in a suitable solvent, in which a resulting inorganic salt, e.g.
silver chloride, is insoluble and thus precipitates out from the reaction mixture.
Depending on the method and/or reaction conditions, the compounds of formula
(I) with salt-forming characteristics can be obtained in free form or in the form of salts.
Compounds of formula (I) can also be obtained in the form of their hydrates and/or also
can include other solvents, used for example where necessary for the crystallisation of
compounds present in solid form.
As mentioned before, the compounds of formula (I) may be optionally present as
optical and/or geometric isomers or as a mixture thereof. The present disclosure relates
both to the pure isomers and to all possible isomeric mixtures, and is hereinbefore and
hereinafter understood as doing so, even if stereochemical details are not specifically
mentioned in every case.
Diastereoisomeric mixtures of compounds of formula (I), which are obtainable by
the process or in another way, may be separated in known manner, on the basis of the
physical-chemical differences in their components, into the pure diastereoisomers, for
example by fractional crystallisation, distillation and/or chromatography.
Splitting of mixtures of enantiomers, that are obtainable accordingly, into the pure
isomers, may be achieved by known methods, for example by recrystallisation from an
optically active solvent, by chromatography on chiral adsorbents, e.g. high-pressure liquid
chromatography (HPLC) on acetyl cellulose, with the assistance of appropriate micro-
organisms, by cleavage with specific immobilised enzymes, through the formation of
inclusion compounds, e.g. using chiral crown ethers, whereby only one enantiomer is
complexed.
The compounds of the formula (I), wherein n is 0, may be prepared, for example,
by reaction of a compound of formula
NR - S(O) - T
(II)
wherein R , R , T and Y are each as defined above and LG is a leaving group, for
example halogen such as bromine, with a compound of formula
B(OH)
(III),
in the presence of a palladium catalyst, wherein A is defined above. The details of this
palladium-catalyzed carbon-carbon bond forming reaction, called Suzuki reaction, are
known from textbooks of organic chemistry.
The compounds of formula (II) are known or may be prepared according to
known processes, for example by reacting a compound of formula
NR - S(O) - T
(IV)
with a compound of formula
(V),
wherein LG’ is a leaving group, for example halogen, C -C -alkoxy or hydroxyl, and the
further variables each have the above mentioned meaning. The amide formation from an
carboxylic acid or an derivative thereof with an amine is known from textbooks of
organic chemistry. The compounds of formula (IV) are known or may be prepared
according to known processes, for example by reacting the corresponding amine with
methane sulfonyl chloride in known manner. The componds of formula (III) and (V) are
known compounds which are commercially available.
Certain compounds of the formula (I), wherein n is 0, may also be prepared, for
example, by reaction of a compound of formula
NR Y
NR - S(O) - T
(IIa)
wherein R , R , T and Y are each as defined above and LG is a leaving group, for
example halogen such as bromine or chlorine, with a compound of formula
(IIIa),
wherein A* is a heterocyclic radical A and the H-atom is attached to a heteroatom, for
example N or O, by way of an electrophilic substitution at the phenyl ring. The
compounds of formula (IIa) may be obtained in analogy to the compounds of formula of
formula (II) above.
The compounds of the formula (I), wherein n is 1, may be prepared, for example,
by reaction of a compound of formula
(VI)
with a compound of formula
(VII),
wherein the variables are as defined above, followed by the reduction of the nitro group
and further reacting the resulting amine with methane sulfonyl chloride. The details of
these reactions are known from textbooks of organic chemistry. The compounds of
formula (VI) may be prepared in analogy to the compounds of formula (II). The
compounds of formula (VII) are known per se and are commercially available.
The compounds of the formula (I), wherein n is 1 may also be prepared by
reaction of a compound of formula
(VIII)
with a compound of formula
(V),
wherein the variables each have the above given meaning, followed by the reduction of
the nitro group and further reacting the resulting amine with methane sulfonyl chloride. In
the alternative, the nitro group of the compound of formula (VIII) may first of all be
reduced and the resulting amino group be reacted with methane sulfonyl chloride, before
the reaction with the compound of formula (V) is performed.
The compounds of formula (VIII) may be prepared in a manner known per se, for
example by reaction of a compound of formula
(IX) with a compound of formula (VIIa).
The Examples further illustrate the different synthesis methods.
The compounds of formula (I) according to the present disclosure are notable for
their broad activity spectrum and are valuable active ingredients for use in pest control,
including in particular the control of endoparasites, especially helminths, in and on warm-
blooded animals, especially productive livestock and pets, whilst being well-tolerated by
warm-blooded animals and fish.
Productive livestock includes mammals such as, for example, cattle, horses,
sheep, pigs, goats, donkeys, rabbits, deer, as well as birds, for example chickens, geese,
turkeys, ducks and exotic birds.
Pets include, for example, dogs, cats and hamsters, in particular dogs and cats.
The compounds of formula (I) of the present disclosure are effective against helminths, in
which the endoparasitic nematodes and trematodes may be the cause of serious diseases
of mammals and poultry. Typical nematodes of this indication are: Filariidae, Setariidae,
Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris,
Bunostonum, Oesophagostonum, Charbertia, Trichuris, Strongylus, Trichonema,
Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma,
Uncinaria, Toxascaris and Parascaris. The trematodes include, in particular, the family
of Fasciolideae, especially Fasciola hepatica (liver fluke).
It could also be shown surprisingly and unexpectedly that the compositions
described herein have exceptionally high efficacy against nematodes that are resistant to
many active substances. This can be demonstrated, for example in vitro by the LDA test.
Certain pests of the species Nematodirus, Cooperia and Oesophagostonum infest
the intestinal tract of the host animal, while others of the species Haemonchus and
Ostertagia are parasitic in the stomach and those of the species Dictyocaulus are parasitic
in the lung tissue. Parasites of the families and may be found in the internal cell tissue and
in the organs, e.g. the heart, the blood vessels, the lymph vessels and the subcutaneous
tissue. A particularly notable parasite is the heartworm of the dog, Dirofilaria immitis.
The compounds of formula (I) described herein are highly effective against these
parasites.
The pests which may be controlled by the compounds of formula (I) described
herein also include those from the class of Cestoda (tapeworms), e.g. the families
Mesocestoidae, especially of the genus Mesocestoides, in particular M. lineatus;
Dipylidiidae, especially Dipylidium caninum, Joyeuxiella spp., in particular Joyeuxiella
pasquali, and Diplopylidium spp., and Taeniidae, especially Taenia pisiformis, Taenia
cervi, Taenia ovis, Taeneia hydatigena, Taenia multiceps,Taenia taeniaeformis, Taenia
serialis, and Echinococcus spp., most preferably Taneia hydatigena, Taenia ovis, Taenia
multiceps, Taenia serialis; Echinococcus granulosus and Echinococcus multilocularis.
Furthermore, the compounds of formula (I) are suitable for the control of human
pathogenic parasites. Of these, typical representatives that appear in the digestive tract are
those of the genus Ancylostoma, Necator, Ascaris, Strongyloides, Trichinella, Capillaria,
Trichuris and Enterobius. The compounds described herein are also effective against
parasites of the genus Wuchereria, Brugia, Onchocerca and Loa from the family of
Dracunculus and parasites of the genus Strongyloides and Trichinella, which infect the
gastrointestinal tract in particular.
The good endoparasiticidal activity of the compounds of formula (I) corresponds
to a mortality rate of at least 50-60%, in particular at least 80% and especially at least
90% of the endoparasites mentioned.
Administration of the compounds of formula (I) described herein may be effected
therapeutically or preferably prophylactically.
Application of the compounds of formula (I) described herein to the animals to be
treated may take place, for example, topically, perorally, parenterally or subcutaneously.
A preferred embodiment described herein relates to compounds of formula (I) for
parenteral use or, in particular, for peroral use.
Preferred application forms for usage on warm-blooded animals in the control of
nematodes/ helminths comprise solutions; emulsions including classical emulsions,
microemulsions and self-emulsifying compositions, that are waterless organic, preferably
oily, compositions which form emulsions – together with body fluids - upon addition to
an animal body; suspensions (drenches); pour-on formulations; food additives; powders;
tablets including effervescent tablets; boli; capsules including micro-capsules; and
chewable treats; whereby the physiological compatibility of the formulation excipients
must be taken into consideration. Particularly preferred application forms are tablets,
capsules, food additives or chewable treats.
The compounds of formula (I) described herein are employed in unmodified form
or preferably together with adjuvants conventionally used in the art of formulation and
may therefore be processed in a known manner to give, for example, emulsifiable
concentrates, directly dilutable solutions, dilute emulsions, soluble powders, powder
mixtures, granules or microencapsulations in polymeric substances. As with the
compositions, the methods of application are selected in accordance with the intended
objectives and the prevailing circumstances.
The formulation, i.e. the agents, preparations or compositions containing the one
or more active ingredients and optionally a solid or liquid adjuvant, are produced in a
manner known per se, for example by intimately mixing and/or grinding the active
ingredients with the adjuvants, for example with solvents, solid carriers and/or surface-
active compounds (surfactants).
The solvents in question may be: alcohols, such as ethanol, propanol or butanol,
and glycols and their ethers and esters, such as propylene glycol, dipropylene glycol
ether, ethylene glycol, ethylene glycol monomethyl or -ethyl ether, ketones, such as
cyclohexanone, isophorone or diacetanol alcohol, strong polar solvents, such as N-
methylpyrrolidone, dimethyl sulfoxide or dimethylformamide, or water, vegetable oils,
such as rape, castor, coconut, or soybean oil, and also, if appropriate, silicone oils.
Suitable surfactants are, for example, non-ionic surfactants, such as, for example,
nonylphenolpolyethoxyethanols; castor oil polyglycol ethers, for example macrogol
glycerolhydroxystearate 40; polyethylene glycols; polypropylene/polyethylene oxide
adducts; or fatty acid esters of polyoxyethylene sorbitan, e.g. polyoxyethylene sorbitan
monooleate.
Solid carriers, for example for tablets and boli, may be chemically modified
polymeric natural substances that are soluble in water or in alcohol, such as starch,
cellulose or protein derivatives (e.g. methyl cellulose, carboxymethyl cellulose,
ethylhydroxyethyl cellulose, proteins such as zein, gelatin and the like), as well as
synthetic polymers, such as polyvinyl alcohol, polyvinyl pyrrolidone etc. The tablets also
contain fillers (e.g. starch, microcrystalline cellulose, sugar, lactose etc.), glidants and
disintegrants.
If the anthelminthics are present in the form of feed concentrates, then the carriers
used are e.g. performance feeds, feed grain or protein concentrates. Such feed
concentrates or compositions may contain, apart from the active ingredients, also
additives, vitamins, antibiotics, chemotherapeutics or other pesticides, primarily
bacteriostats, fungistats, coccidiostats, or even hormone preparations, substances having
anabolic action or substances which promote growth, which affect the quality of meat of
animals for slaughter or which are beneficial to the organism in another way.
Suitable compositions of the compounds of formula (I) may also contain further
additives, such as stabilisers, antioxidants, for example tocopherols like α-tocopherol,
anti-foaming agents, viscosity regulators, binding agents, colors or tackifiers, as well as
other active ingredients, in order to achieve special effects. Preferably, the composition
comprises from 0.001 to 1 % w/v of one or more antioxidants. If desired, the formulations
described herein may comprise a color, for example in an amount of from 0.001 to 1 %
w/v.
As a rule, an anthelminthic composition described herein contains 0.1 to 99 % by
weight, especially 0.1 to 95 % by weight of a compound of formula (I), 99.9 to 1 % by
weight, especially 99.8 to 5 % by weight of a solid or liquid admixture, including 0 to
% by weight, especially 0.1 to 25 % by weight of a surfactant.
In each of the processes described herein for pest control or in each of the pest
control compositions described herein, the compounds of formula (I) can be used in all of
their steric configurations or in mixtures thereof.
Also described is a method of prophylactically protecting warm-blooded animals,
especially productive livestock and pets, in particular dogs or cats, against parasitic
helminths, which is characterised in that a compound of formula (I) or the active
ingredient formulation prepared therefrom is administered to the warm-blooded animal as
an additive to the feed, or to the drinks or also in solid or liquid form, orally or by
injection or parenterally. Also described are compounds of formula (I) described herein
for usage in one of the said processes.
The compounds of formula (I) described herein may be used alone or in
combination with other biocides. They may be combined with pesticides having the same
sphere of activity e.g. to increase activity, or with substances having another sphere of
activity e.g. to broaden the range of activity. It can also be sensible to add so-called
repellents.
The following Examples illustrate the invention further.
Analysis of the purified samples is in each case done using a Waters
Autopurification (HPLC/MS) system with a reversed phase column using method B
described below. The samples are characterized by m/z and retention time. The above-
given retention times relate in each case to the use of a solvent system comprising two
different solvents, solvent A: H O + 0.01% HCOOH, and solvent B: CH CN + 0.01%
HCOOH).
- Method B: column Waters XTerra MS C18 5μm, 50X4.6mm (Waters), flow rate
of 3.00 mL/min with a time-dependent gradient as given in the Table:
Time [min] A [%] B [%]
0 90 10
0.5 90 10
2.5 5 95
2.8 5 95
2.9 90 10
3.0 90 10
Example 1A
Synthesis of 2-(methylsulfonamido)morpholino-N-(3,4,5-trichlorophenyl)benzamide
(Ex.1.2 in Table 1)
Step A: 5-chloronitro-N-(3,4,5-trichlorophenyl) benzamide.
-chloronitrobenzoic acid (10 g) was treated with thionyl chloride (7.2 mL) at reflux
for 4h. Excess SOCl2 was removed under vacuum. CH2Cl2 (100 mL) was added to the
acyl chloride. At 0°C, 3,4,5-trichloroaniline (9.7 g) and NEt (13.8 mL) in 100 mL
CH2Cl2 were added slowly. The reaction mixture was allowed to warm up and it was
stirred at rt (room temperature) overnight. The reaction mixture was diluted with 200 mL
diethyl ether. 10 mL HCl 2 N and 200 mL H2O were added, and the mixture was stirred
until a yellow precipitate is formed. The precipitate was filtered off and dried under high
vacuum before analysis (yield: 66%). LCMS (method B): 380.59 (M+H) at 1.97 min.
Step B: 5-morpholinonitro-N-(3,4,5-trichlorophenyl)benzamide
To a solution of 300 mg of 5-chloronitro-N-(3,4,5-trichlorophenyl)benzamide in 1.5
mL DMF, was added morpholine (206 μL). The reaction mixture was heated at 110°C for
1.5 h. After work-up and extraction with AcOEt, the mixture was evaporated to dryness.
The title compound was pure enough to be engaged in step B. (yield: 71%). LCMS
(method B): 427.7 (M-H) at 1.81 min.
Step C: 2-aminomorpholino-N-(3,4,5-trichlorophenyl)benzamide
Under N , 5-morpholinonitro-N-(3,4,5-trichlorophenyl)benzamide (230 mg) in 4 mL
EtOH/H O (3/1) was treated with Fe (208 mg) and HCl 25% (4 μL) and the reaction
mixture was stirred at rt for 4 h. When the reduction was completed, the reaction mixture
was filtered on a plug of celite and washed with ethyl acetate. The filtrate was evaporated
under vacuum. Ethyl acetate was added, and the organic layer was washed with brine,
dried over MgSO , and evaporated to dryness (yield: 95%). LCMS (method B): 399.68
(M+H) at 1.61 min.
Step D: 2-(methylsulfonamido)morpholino-N-(3,4,5-trichlorophenyl)benzamide
A N degassed solution of 2-aminomorpholino-N-(3,4,5-trichlorophenyl)benzamide
(193 mg) in 3 mL CH2Cl2, pyridine (0.194 mL) was added. The mixture was cooled to
0°C before the drop wise addition of methane sulfonyl chloride (0.037 mL). The reaction
mixture was stirred overnight at rt, then diluted with 50 mL ethyl acetate. The organic
layer was washed with a saturated solution of Na CO , with brine, then dried over MgSO
2 3 4
and evaporated to dryness (yield: 43%). LCMS (method B): 477.7 (M+H) at 1.78 min.
Example 1B
N-(3,5-bis (trifluoromethyl) phenyl)(2-fluoropyridinyl)(methylsulfonamido)
benzamide (Ex.1.14 in Table 1)
Step A: methyl 5-bromo(methylsulfonamido) benzoate.
A N degassed solution of methyl 2-aminobromobenzoate (2.8 g) in 10 mL 1 pyridine
was cooled to 0°C before the drop wise addition of methane sulfonyl chloride (0.9 mL).
The reaction mixture was stirred overnight at rt, then diluted with 50 mL ethyl acetate.
The organic layer was washed with a saturated solution of Na CO , with brine, then dried
over MgSO and evaporated to dryness (yield: 82%). LCMS (method B): 305.6 (M-H) at
1.55 min.
Step B: 5-bromo(methylsulfonamido)benzoic acid
Methyl 5-bromo(methylsulfonamido) benzoate (3.15 g) was suspended in THF (20
mL, 1/1). NaOH 4 N (6.9 mL) was added and the reaction mixture was stirred 4h at
reflux. Upon completion, the reaction mixture was treated with 2N HCl (1mL) and
extracted twice with ethyl acetate. Combined organic layers were washed with H O,
brine, dried over Na SO , filtered and evaporated to dryness. The title product was pure
enough by LCMS to be engaged into next step without further purification. (yield: 66%)
LCMS (method B): 291.64 (M-H) at 1.2 min.
Step C: N-(3,5-bis(trifluoromethyl)phenyl)bromo(methylsulfonamido)benzamide.
5-bromo(methylsulfonamido) benzoic acid (2.4 g) was treated with thionyl chloride
(23 mL) at reflux for 4h. Excess SOCl was removed under vacuum. CH Cl (20 mL) was
2 2 2
added to the acyl chloride. At 0°C, 3,5-bis(trifluoromethly)aniline (1.4 mL) and NEt
(5.68 mL) in 10 mL CH Cl were added slowly. The reaction mixture was allowed to
warm up and it was stirred at rt overnight.
The reaction mixture was diluted with 30 mL CH Cl . 20 mL HCl 2 N and 20 mL H O
2 2 2
were added, and the mixture was stirred until a yellow precipitate is formed. The
precipitate was filtered off and dried under high vacuum before analysis (yield: 67%).
LCMS (method B): 502.93 (M-H) at 1.99 min.
Step D: N-(3,5-bis (trifluoromethyl) phenyl)(2-fluoropyridinyl)
(methylsulfonamido) benzamide.
To a solution of N-(3,5-bis(trifluoromethyl)phenyl)bromo(methylsulfonamido)
benzamide (0.2 g) and 2-Fluoro(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)pyridine
(133 mg) under N in dioxane/H O (6 mL, 1/1) was added Na CO (252 mg),
2 2 2 3
Pd(dppf)Cl .CH Cl (355 mg). The reaction mixture was stirred for 3h at 80°C. It was
2 2 2
diluted with ethyl acetate, filtered through celite. The filtrate was washed with H O,
brine, dried over Na SO , filtered and evaporated to dryness.
The crude mixture was purified by flash chromatography eluting with a gradient of 100%
heptane to 60% heptane/40% ethyl acetate to offer the title compound in 25% yield.
LCMS (method C): 521.8 (M+H) at 1.90 min.
The substances named in the following Table 1 are prepared analogously to the
above-described methods. The compounds are of formula
(R )
NH-SO CH
wherein the meaning of A and (R) is given in Table 1.
The following physical data are obtained according to the above-described
HPLC/MS characterization process (method B). R refers to “retention time”.
Table 1:
Ex. m/z: R [min] Physical
A (R )
No. [M+H ] (Method B) state
1.2 Morpholinyl 3,4,5-tri-Cl 477.7 1.78 Solid
1.3 4-Methylpiperazinyl 3,4,5-tri-Cl 490.9 1.29 Solid
1.4 Thiazinyl 3,4,5-tri-Cl 493.7 1.97 Solid
1.5 Pyrrolidinyl 3,4,5-tri-Cl 461.7 2.04 Foam
1.6 Pyrazolyl 3,4,5-tri-Cl 458.8 1.89 Powder
1.7 Isopropyl 3,5-di-CF3 468.8 2.07 Powder
1.8 CF 3,5-di-CF 494.5 1.99 Oil
1.9 3,5-di-CF 552.9 2.22 Powder
3,5-di-CF
1.10 3 550.7 1,99 Powder
3,5-di-CF3
1.11 534.8 1.78 Solid
1.12 506.7 1.79 Powder
3,5-di-CF
1.13 607.9 1.27 Resin
3,5-di-CF3
3,5-di-CF
1.14 521.8 1.90 Powder
1.15 3,5-di-CF 542.8 1.85 Powder
1.16 521.7 1.94 Powder
3,5-di-CF
1.17 571.7 2.06 Foam
3,5-di-CF
3,5-di-CF
1.18 537.7 2.00 Powder
3,5-di-CF
1.19 571.6 2.10 Powder
1.20 551.7 2.06 Powder
3,5-di-CF
H CÔ
1.21 533.7 2.02 Powder
3,5-di-CF
1.22 538.7 1.93 Powder
3,5-di-CF
N 3,5-di-CF
H CÔ
1.23 534.7 1.85 Powder
1.24 504.8 1.71 Powder
3,5-di-CF
1.25 537.8 1.90 Solid
3,5-di-CF
N 3,5-di-CF
1.26 537.8 1.89 Foam
H C-H C-Ô
1.27 548.0 2.08 Powder
3,5-di-CF
1.28 529.0 1.89 Powder
3,5-di-CF
3,5-di-CF
1.29 537.9 1.94 Powder
1.30 542.9 2.28 Powder
3,5-di-CF3
1.31 572.9 2.11 Powder
3,5-di-CF3
3,5-di-CF3
1.32 571.8 2.05 Powder
3,5-di-CF
1.33 537.7 1.99 Resin
Example 2
-phenoxy(phenylsulfonamido)-N-(3,4,5-trichlorophenyl)benzamide
(Ex.2.2 in Table 2)
Step A: 2-nitrophenoxy-N-(3,4,5-trichlorophenyl)benzamide.
-Chloronitro-N-(3,4,5-trichlorophenyl) benzamide (29.1 g), K CO (21.3 g) and
phenol (8 g) in DMA were heated at 140°C during 14h. The reaction mixture was poured
in H O (100 mL), the precipitate was filtered off, dried under high vacuum to afford a
brown solid (yield: 80%). LCMS (method B): 436.6 (M-H) at 2.14 min.
Step B: 2-aminophenoxy-N-(3,4,5-trichlorophenyl)benzamide
2-nitrophenoxy-N-(3,4,5-trichlorophenyl)benzamide treated with iron in a similar
manner as described for step C Example 1 (yield: 27%). LCMS (method B): 406.7
(M+H) at 2.28 min.
Step C: 5-(4-Chlorophenoxy)(methylsulfonamido)-N-(3,4,5-trichlorophenyl)
benzamide
To N degassed solution of 2-aminophenoxy-N-(3,4,5-
trichlorophenyl)benzamide (0.26 mg) in 2mL of CH Cl , pyridine (0.25 mL) was added.
The mixture was cooled to 0°C before the drop wise addition of benzene sulfonyl chloride
(0.124 mg). The reaction mixture was stirred overnight at rt, then diluted with additional
mL CH2Cl2. The organic layer was washed with a saturated solution of Na2CO3, with
brine, then dried over MgSO and evaporated to dryness (yield: 81%). LCMS (method
B): 546.7 (M+H) at 2.39 min.
The substances named in the following Table 2 are prepared analogously to the
above-described methods. The compounds are of formula
NR -SO T
wherein the meaning of (R ) , (R) , and X are given in Table 2
The following physical data are obtained according to the above-described HPLC/MS
characterization process (Method B).
Table 2:
m/z: Physical
(R) T [M+H ] state
[min]
4-Cl 4-CH -phenyl
2.1 594.6 2.22 Powder
2.2 H phenyl 546.7 2.39 Powder
2.3 4-Cl 2-NO CF -phenyl 693.6 1.88 Gum
2.4 4-Cl 3-ClF-phenyl 632.5 2.57 Solid
2.5 4-Cl 2-CF3F-phenyl 666.5 2.59 Solid
2.6 4-Cl 4-CF -phenyl 648.5 2.58 Solid
2.7 4-Cl 3,4-dimethoxyphenyl 640.6 2.40 Solid
2.8 4-Cl 4-nitrophenyl 625.5 2.46 Solid
2.9 4-Cl 4-chlorophenyl 614.7 2.59 Solid
2.10 4-Cl 3,5-di-Cl-phenyl 2.78 Solid
648.5
2.11 4-Cl 4-methoxyphenyl 610.6 2.46 Solid
2.12 4-Cl 2-Chloro-phenyl 614.5 2.57 Solid
2.13 4-Cl 3-Chlorophenyl 614.7 2.60 Solid
2.14 4-Cl 3-Pyridyl 581.6 2.31 Solid
2.15 4-Cl 3-methoxyphenyl 610.6 2.49 Solid
4-Cl 3,4-dichlorophenyl H
2.16 648.5 2.71 Solid
4-Cl 2,6-dichlorophenyl H
2.17 648.6 2.66 Solid
4-Cl 2-methoxyphenyl H
2.18 610.6 2.43 Solid
4-Cl 2,4-dichlorophenyl H
2.19 648.6 2.74 Solid
4-Cl 2-NO OCH -phenyl H
2.20 655.5 2.42 Powder
4-Cl 2,4-dimethoxyphenyl H
2.21 640.6 2.41 Solid
4-Cl ethyl H
2.22 532.5 2.37 Solid
4-Cl -CH CF H
2.23 586.4 2.39 Powder
4-Cl -CH CH CF H
2 2 3
2.24 598.5 2.47 Solid
4-Cl n-propyl H
2.25 2.44 Solid
546.6
4-Cl n-butyl H
2.26 560.7 2.52 Solid
4-Cl Iso-butyl H
2.27 560.7 2.51 Powder
4-Cl -CH CH Si(CH ) H
2 2 3 3
2.28 604.7 2.68 Powder
4-Cl Cyclopropyl H
2.29 544.6 2.36 Powder
4-Cl Cyclohexyl H
2.30 586.6 2.65 Powder
4-Cl 1-(benzyloxycarbonyl)- H
2.31 721.8 2.54 Powder
piperazinyl
4-Cl Isopropyl H
2.32 546.6 2.23 Solid
4-Cl Cyclohexylmethyl H
2.33 600.6 2.74 Solid
4-Cl (1R)-(-)-Campher H
2.34 654.7 2.57 Solid
4-Cl -CH C(O)OC H H
2 2 5
2.35 590.6 2.36 Solid
4-Cl -CH C(O)OCH H
2.36 576.6 2.29 Foam
4-Cl -CH C(O)OH H
2.37 2.16 Solid
562.5
4-Cl (1S)-(+)-Campher H
2.38 654.8 2.55 Solid
4-Cl Tetrahydro-2H-pyranyl H
2.39 588.6 2.33 Solid
4-Cl -N(CH ) H
2.40 547.6 2.40 Powder
4-Cl 1-Methylpiperazinyl H
2.41 602.8 1.72 Powder
4-Cl O H
2.42 637.6 2.24 Powder
4-Cl -CH -Cl -SO CH Cl
2 2 2
2.43 664.4 2,44 Solid
4-Cl
2.44 644.6 1.52 Powder
CH N N CH H
4-Cl
2.45 775.6 2.63 Powder
CH N N CF H
4-Cl
2.46 757.8 1.59 Powder
NO H
N N CH
4-Cl
2.47 744.7 2.41 Powder
O CH H
N N CH
CH 3
4-Cl
2.48 740.6 2.68 Powder
CH N N Cl H
Example 3
2-(methylsulfonamido)-N-(3,4,5-trichlorophenyl)((2-(trifluoromethyl)pyridin
yl)oxy)benzamide (Ex 3.2 in Table 3)
Step A: methyl 2-nitro((2-(trifluoromethyl) pyridinyl)oxy)benzoate.
Methyl 5-chloronitrobenzoate was treated in a similar manner as step A of synthesis of
example 3 (yield: 28%). LCMS (method B): 342.86 (M+H) at 1.63 min.
Step B: 2-nitro((2-(trifluoromethyl) pyridinyl)oxy)benzoic acid.
Methyl 2-nitro((2-(trifluoromethyl) pyridinyl)oxy)benzoate (277 mg) was treated
overnight at rt with NaOH 1N (4.13 mL) in THF/MeOH (8 mL, 2/1) (yield: 98%). LCMS
(method B): 328.84 (M+H) at 1.33 min.
Step C: 2-nitro -N- (3,4,5-trichlorophenyl) ((2-(trifluoromethyl)pyridinyl)oxy)
benzamide
2-nitro((2-(trifluoromethyl) pyridinyl) oxy) benzoic acid was treated in a similar
manner as step A of synthesis of example 1 (yield: 45%). LCMS (method B): 505.7
(M+H) at 2.05 min.
Step D: 2-amino -N- (3,4,5-trichlorophenyl) ((2-(trifluoromethyl) pyridine yl)oxy)
benzamide 2-nitro-N-(3,4,5-trichlorophenyl)((2-(trifluoromethyl) pyridinyl) oxy)
benzamide was treated in a similar manner as step C Example 1 (yield: 100%). LCMS
(method B): 475.52 (M+H) at 2.21 min.
Step E: 2-(methylsulfonamido)-N-(3,4,5-trichlorophenyl)((2-(trifluoromethyl)pyridin-
3-yl)oxy) benzamide 2-amino-N-(3,4,5-trichlorophenyl)((2-(trifluoromethyl) pyridine -
3- yl) oxy) benzamide was treated in a similar manner as step D of synthesis of example 1
(yield: 20%). LCMS (method C): 553.7 (M+H) at 2.07 min.
The substances named in the following Table 3 are prepared analogously to the
above-described methods. The compounds are of formula
NH-SO CH
wherein the meaning of A given in Table 3. The following physical data are obtained
according to the above-described HPLC/MS characterization process.
Table 3:
m/z: [M+H ]
R [min] R [min]
(Method) (Method)
3.1 556.7 2.09 (B) Solid
3.2 553.7 2.07 (B) Solid
3.3 N 551.7 3.95 (A) Foam
3.4 558.8 2.95 (C) Solid
Example 4
-(4-chlorophenoxy)(methylsulfonamido)-N-(4-(trifluoromethyl)oxazol
yl)benzamide
(Ex 4.16 in Table 4)
Step A: methyl 5-(4-chlorophenoxy)nitrobenzoate
methyl 5-chloronitrobenzoate was treated in a similar manner as step A of synthesis of
example 3 (yield: 90%). LCMS (method B): 305.0 (M+H) at 1.67 min.
Step B: methyl 2-amino(4-chlorophenoxy) benzoate
methyl 5-(4-chlorophenoxy)nitrobenzoate was treated in a similar manner as step C
Example 1 (yield: 100%). LCMS (method B): 277.82 (M+H) at 1.88 min.
Step C: methyl 5-(4-chlorophenoxy)(methylsulfonamido) benzoate
methyl 2-amino(4-chlorophenoxy)benzoate was treated in a similar manner as step D
of synthesis of example 1 (yield: 95%). LCMS (method B): 353.78 (M-H) at 1.84 min.
Step D: 5-(4-chlorophenoxy)(methylsulfonamido) benzoic acid
methyl 5-(4-chlorophenoxy)(methylsulfonamido)benzoate was saponified in a similar
manner as step B of synthesis of example 4 (yield: 96%). LCMS (method B): 339.62 (M-
H) at 1.61 min.
Step E: 5-(4-chlorophenoxy)(methylsulfonamido)-N-(4-(trifluoromethyl) oxazol
yl)benzamide
-(4-chlorophenoxy)(methylsulfonamido) benzoic acid was treated in a similar manner
as step A of synthesis of example 1 (yield: 3%). LCMS (method B): 475.64 (M+H) at
1.70 min.
The substances named in the following Table 4 are prepared analogously to the
above-described methods. The compounds are of formula
NH-SO -CH
Cl 2 3
wherein the meaning of Y and R is given in Table 4. The following physical data are
obtained according to the above-described HPLC/MS characterization process (Method
Table 4:
m/z:
R [min] R [min]
Y R [M+H ]
(Method) (Method B)
4.1 503.7 1.94 Powder
4.2 447.7 1.99 Solid
4.3 482.6 1.94 Solid
C(O)OC H
4.4 495.6 1.76 Solid
4.5 423.6 1.69 Solid
4.6 468.6 1.79 Powder
4.7 492.7 1.83 Solid
4.8 487.6 1.99 Solid
N 3 H
4.9 509.7 1.95 Solid
C(O)OC H
4.10 608.6 1.85
Solid
SO NO
C(O)OC H
4.11 508.6 2.32
Solid
4.12 563.6. 2.00
Solid
C(O)OC H
4.13 540.5 2.05
N H Solid
H Solid
4.14 571.7 2.20
C(O)OC H
4.15 437.7 1.67
H Solid
4.16 475.6 1.70 Oil
4.17 417.8 1.45
N H Oil
4.18 447.7 2.20
H Oil
H Oil
4.19 465.7 1.47
N H Oil
4.20 451.7 1.71
H Oil
4.21 485.8 1.90
4.22 431.7 1.25 Powder
4.23 496.9 2.06 Foam
4.24 541.7 2.07 Solid
4.25 3 543.8 2.09 Solid
4.26 O 472.7 1.62 Solid
4.27 455.8 1.71 Solid
4.28 H 467.8 1.73 Solid
4.29 475.8 1.51 Solid
4.30 500.8 1.77 Solid
Cl CF
H Solid
4.31 567.6 2.08
H Solid
4.32 510.7 1.78
Cl Cl
4.33 533.6 2.09 Oil
4.34 479.7 1.89 Powder
N Cl
H Oil
4.35 461.8 1.78
H Oil
4.36 465.7 1.82
4.37 499.7 1.89
H Oil
N Cl
4.38 456.7 1.65
H Oil
4.39 509.7 1.75
H Oil
N CH
4.40 423.7 0.61
Powder
N OCH
4.41 515.7 1.67
Foam
4.42 595.7 1.93
Powder
O OCH
4.43 636.8 1.62
Solid
4.44 435.7 1.48
H C N
2 H Solid
4.45 479.7 1.56
H C N CF
H Solid
4.46 436.7 1.46
H C N
2 H Solid
H Oil
4.47 480.7 1.74
Solid
4.48 512.7 1.85
4.49 456.8 1.95
H Resin
H Solid
4.50 513.7 1.76
H C CH
3 3 H
Foam
4.51 477.0 3.09
4.52 434.8 2.02
OH Solid
4.53 481.7 3.27
Biological Examples:
Gastro-intestinal Larval Development Assay
Freshly harvested and cleaned nematode eggs are used to seed a suitably
formatted well plate containing the test substances to be evaluated for antiparasitic
activity and media allowing the full development of eggs through to 3rd instar larvae. The
plates are incubated for 6 days at 25°C and 60% relative humidity. Egg-hatching and
ensuing larval development are recorded to identify a possible nematodicidal activity.
Efficacy is expressed in percent reduced egg hatch, reduced development of L3, or
paralysis & death of larvae at any stage. Compounds Nos. 1.4, 1.10-1.12, 1.14, 1.16-1.21,
1.23, 1.25-1.26, 1.29-1.33, 2.1, 2.22, 2.28, 2.42-2.43, 3.1-3.2, 4.1, 4.3-4.8, 4.19-4.24,
4.28, 4.32, 4.34, 4.36-4.37, 4.39, 4.42-4.43 and 4.51 reached ≥ 60% efficacy at 10ppm,
and are therefore considered active.
Dirofilaria immitis microfilaria assay
Freshly harvested and cleaned Dirofilaria immitis microfilariae are prepared from
blood from donor animals dogs. The microfilariae are then distributed in formatted
microplates containing the test substances to be evaluated for antiparasitic activity. The
plates are incubated for 48 hours at 25°C and 60% relative humidity (RH). Motility of
microfilariae is then recorded to determine efficacy. Efficacy is expressed in percent
reduced motility as compared to the control and standards. Compounds Nos. 1.2-1.4 and
1.6 to 1.33, 2.1-2.20, 2.22-2.44, 2.46, 3.1-3.4, 4.1-4.10, 4.12-4.16, 4.17-4.18, 4.21-4.29,
4.31-4.39, 4.42 and 4.46-4.52 showed an efficacy above 50% at 10 ppm, and are therefore
considered active.
Acanthocheilonema viteae in Gerbil
Gerbils are artificially infected with 80 L3 larvae of A. viteae by subcutaneous
injection. Treatment by gavage with the formulated test compounds occurs consecutively
day 5 to day 9 after infection. Eighty-four days after infection, gerbils are bled for
counting circulating microfilariae, using a Fuchs-Rosenthal counting chamber and
microscope. Only test groups with an average of circulating microfilariae at least 50%
lower than in the placebo treated group are fully dissected to recover adult worms.
Efficacy is expressed as a % reduction in worm numbers in comparison with the placebo
treated group, using the Abbot’s formula. Compound No. 1.6-1.8, 1.17, 1.25, 1.30, 1.32,
2.24, 4.13, 4.24 showed an efficacy above 80% at 10 mg/kg.
Adult liver fluke-in vitro assay
Freshly harvested adult Fasciola hepatica from cattle or sheep livers were
distributed in 12-well plates (1 fluke per well) with 4 mL of RPMI complete medium and
kept in an incubator at 37°C for approximately 12 hours. After renewal of the medium,
the viability of the flukes is determined by video-registration of the movement of the
individual flukes (pre-value). Test compounds are added at a concentration of 100 µg/mL
and the movements of the flukes are measured after 6 and 24 hours. Efficacy is expressed
as percent reduced movement based on the pre-value and the untreated control. In this test
the following examples showed more than >90% efficacy after 6 h and >95% after 24 h
are considered as positive: 2.2, 4.13.
The term “comprising” as used in this specification and claims means “consisting
at least in part of”. When interpreting statements in this specification, and claims which
include the term “comprising”, it is to be understood that other features that are additional
to the features prefaced by this term in each statement or claim may also be present.
Related terms such as “comprise” and “comprised” are to be interpreted in similar
manner.
In this specification where reference has been made to patent specifications, other
external documents, or other sources of information, this is generally for the purpose of
providing a context for discussing the features of the invention. Unless specifically stated
otherwise, reference to such external documents is not to be construed as an admission
that such documents, or such sources of information, in any jurisdiction, are prior art, or
form part of the common general knowledge in the art.
In the description in this specification reference may be made to subject matter
that is not within the scope of the claims of the current application. That subject matter
should be readily identifiable by a person skilled in the art and may assist in putting into
practice the invention as defined in the claims of this application.
Claims (10)
1. A compound of formula NR Y NR - S(O ) - T (I), or a salt or an enantiomer thereof, wherein n is 0 or 1; A is C -C -cycloalkyl; C -C -halocycloalkyl; 5- or 6-membered heterocycloalkyl 3 6 3 6 having from 1 to 3 same or different heteroatoms selected from the group consisting of B, 10 N, O and S, which is further unsubstituted or substituted by halogen, C -C -alkyl or C - 1 4 1 C -alkoxy; or is cinnamyl, which is unsubstituted or substituted in the phenyl moiety by halogen, C -C -alkyl or C -C -alkoxy; or is a heteroaromatic radical, which is further 1 4 1 4 unsubstituted or substituted by halogen, cyano, C -C -alkyl, C -C -haloalkyl, C -C - 1 4 1 4 1 4 alkoxy, C -C -haloalkoxy, C -C -alkanoyl, 5- or 6-membered heterocycloalkyl-C -C - 1 4 2 4 1 2 15 alkyl or unsubstituted or halogen-, C -C -alkyl- or C -C -alkoxy-substituted phenyl; or is 1 4 1 4 a hetero-bicyclic ring radical comprising a total of 8 to 10 ring members, from which 1 to 5 members are same or different heteroatoms selected from the group consisting of B, N, O and S, and from which 0 to 2 members are a group –C(O)-, which bicyclic ring radical is further unsubstituted or substituted by halogen, cyano, hydroxyl, C -C -alkyl or C -C - 1 4 1 4 20 haloalkyl; R is H or –S(O )-T; T is C -C -alkyl which is unsubstituted or substituted by halogen, trimethylsilyl, C -C -cycloalkyl, carboxyl or C -C -alkoxycarbonyl; C -C -cycloalkyl; C -C - 3 6 1 4 3 6 6 12 bicarbocyclyl; a 5- or 6 membered heteroaromatic radical, which is further unsubstituted 25 or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl or C -C -alkoxy; 5- 1 4 1 4 1 4 or 6-membered heterocycloalkyl having from 1 to 3 same or different heteroatoms selected from the group consisting of N, O, S and S(O ), which is further unsubstituted or substituted by C -C -alkyl, C -C -alkoxycarbonyl or benzyloxycarbonyl ; a group 1 4 1 2 CHNN R ; amino; or N-mono- or N,N-di- C -C -alkylamino; R is C -C -alkyl, unsubstituted or halogen-, C -C -alkyl- or C -C -haloalkyl- 1 4 1 4 1 4 substituted phenyl, unsubstituted or halogen-, C -C -alkyl- or C -C -haloalkyl-substituted 1 4 1 4 5 pyridyl, C -C -alkoxycarbonylmethyl or morpholinyl-carbonylmethyl; R is H or hydroxy; and Y is (i) phenyl or a phenylamino, which is substituted by one or more same or different radicals selected from the group consisting of halogen; C -C -alkyl; C -C -haloalkyl; C - 1 6 1 6 3 10 C -cycloalkyl; C -C -halocycloalkyl; hydroxyl; C -C -alkoxy; C -C -haloalkoxy; C -C - 6 3 6 1 6 1 6 1 6 alkylthio; C -C -haloalkylthio; C -C -alkyl-sulfinyl; C -C -haloalkylsulfinyl; C -C - 1 6 1 6 1 6 1 6 alkylsulfonyl; C -C -haloalkylsulfonyl; SF ; amino; N-mono- or N,N-di-C -C - 1 6 5 1 6 alkylamino; tri-C -C -alkylsilyl; C -C -alkoxycarbonyl; aminocarbonyl; N-mono- or 1 4 1 6 N,N-di-C -C -alkylaminocarbonyl; aminosulfonyl; N-mono- or N,N-di-C -C - 1 6 1 6 15 alkylaminosulfonyl; N-C -C -alkylsulfonylamino; C -C -alkoxycarbonylamino; N-C -C - 1 6 1 6 1 4 alkyl-N-C -C -alkoxycarbonylamino; cyano; nitro; and halogen-, C -C -alkyl-, C -C - 1 6 1 4 1 4 haloalkyl-, C -C -alkoxy-, C -C -haloalkoxy-, amino-, cyano- or nitro-substituted C -C - 1 4 1 4 3 6 heterocyclyl; or is (ii) 5- or 6 membered heteroaryl or heteroarylamino, which is each further 20 unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C - 1 4 1 4 1 C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl, or phenyl or phenylsulfonyl which is 4 1 4 2 4 each unsubstituted or substituted by halogen, cyano, nitro, methyl or methoxy; or is (iii) benzoyl or 5- or 6 membered heteroarylcarbonyl, which is each further unsubstituted or substituted by halogen, cyano, nitro, C -C -alkyl, C -C -haloalkyl, C - 1 4 1 4 1 25 C -alkoxy, C -C -alkoxycarbonyl, C -C -alkanoyl or phenyl; or is 4 1 4 2 4 (iv) a C -C -bicarbocyclic radical; or is a 6 12 (v) a radical –H C-C(O)-NH-R , wherein R is C -C -haloalkyl, C -C -alkynyl or 2 1 4 2 3 cyano-C1-C4-alkyl; or R and Y together with the N-atom to which they are attached, form a piperidinyl or piperazinyl radical which is substituted by C -C -alkyl, C -C -alkoxy, unsubstituted or 1 4 1 4 halogen-, C -C -alkyl-, C -C -haloalkyl-, amino- and/or C -C -alkoxy-substituted phenyl 1 4 1 4 1 4 or benzoylamino, or unsubstituted or C -C -alkyl-, C -C -haloalkyl-, C -C -cycloalkyl- or 1 4 1 4 3 6 5 halogen-substituted pyridyl or pyrimidinyl.
2. A compound according to claim 1 of formula NH-SO CH (Ia), wherein Y’ is phenyl which is substituted by one or more same or different radicals 10 selected from the group consisting of halogen; C -C -alkyl; C -C -haloalkyl; C -C - 1 6 1 6 3 6 cycloalkyl; C -C -halocycloalkyl; hydroxyl; C -C -alkoxy; C -C -haloalkoxy; C -C - 3 6 1 6 1 6 1 6 alkylthio; C -C -haloalkylthio; C -C -alkyl-sulfinyl; C -C -haloalkylsulfinyl; C -C - 1 6 1 6 1 6 1 6 alkylsulfonyl; C -C -haloalkylsulfonyl; SF ; amino; N-mono- or N,N-di-C -C - 1 6 5 1 6 alkylamino; tri-C -C -alkylsilyl; C -C -alkoxycarbonyl; aminocarbonyl; N-mono- or 1 4 1 6 15 N,N-di-C -C -alkylaminocarbonyl; aminosulfonyl; N-mono- or N,N-di-C -C - 1 6 1 6 alkylaminosulfonyl; N-C -C -alkylsulfonylamino; C -C -alkoxycarbonylamino; N-C -C - 1 6 1 6 1 4 alkyl-N-C -C -alkoxycarbonylamino; cyano; nitro; halogen-, C -C -alkyl-, C -C - 1 6 1 4 1 4 haloalkyl-, C -C -alkoxy-, C -C -haloalkoxy-, amino-, cyano- or nitro-substituted C -C - 1 4 1 4 3 6 heterocyclyl; and 20 A’ is C -C -cycloalkyl; C -C -halocycloalkyl; 5- or 6-membered heterocycloalkyl 3 6 3 6 having from 1 to 3 same or different heteroatoms selected from the group consisting of B, N, O and S, which is further unsubstituted or substituted by halogen, C -C -alkyl or C - 1 4 1 C -alkoxy; a heteroaromatic radical, which is further unsubstituted or substituted by halogen, cyano, C -C -alkyl, C -C -haloalkyl, C -C -alkoxy, C -C -haloalkoxy, C -C - 1 4 1 4 1 4 1 4 1 4 25 alkanoyl, 5- or 6-membered heterocycloalkyl-C -C -alkyl or unsubstituted or halogen-, C -C -alkyl- or C -C -alkoxy-substituted phenyl; or is a hetero-bicyclic ring radical 1 4 1 4 comprising a total of 8 to 10 ring members, from which 1 to 5, members are same or different heteroatoms selected from the group consisting of B, N, O and S, and from which 0 to 2 members are a group –C(O)-, which bicyclic ring radical is further unsubstituted or substituted by halogen, cyano, hydroxyl, C -C -alkyl or C -C -haloalkyl. 1 4 1 4
3. A compound according to claim 2, wherein Y’ is phenyl which is substituted by 2 5 or 3 same or different radicals selected from halogen or CF ; and A’ is pyrrolidinyl, piperazinyl, morpholinyl or dioxaborolanyl, which is each unsubstituted or substituted by methyl; pyrryl, pyrazolyl, triazolyl, thienyl, thiazinyl, thiazolyl, pyridyl or pyrimidinyl , which is each unsubstituted or substituted by halogen, cyano, C -C -alkyl, C -C -alkoxy, 1 2 1 2 C -C -haloalkyl, acetyl, propionyl, phenyl or morpholinyl-methyl; or indolyl, 10 benzopyrazolyl or benzothiazolyl, which is each unsubstituted or substituted by methyl; and n is 1.
4. A compound according to claim 1, wherein A is morpholinyl, 4- 15 methylpiperazinyl, thiazinyl, pyrrolidinyl, pyrazolyl,
5. The compound according to claim 4, wherein n is 0. 5
6. A compound according to claim 1, wherein A is
7. The compound according to claim 6, wherein n is 1. 10
8. A composition for the control of parasites, which contains as an active ingredient at least one compound of formula (I) according to claim 1, in addition to carriers and/or dispersants.
9. A compound of Formula I as claimed in any one of claims 1-7 substantially as 15 herein described with reference to any example thereof.
10. A composition as claimed in claim 8 substantially as herein described with reference to any example thereof.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP14182960.6 | 2014-08-29 | ||
EP14182960.6A EP2990403A1 (en) | 2014-08-29 | 2014-08-29 | Anthranilamides, sulfonamides and nitro analogues derived therefrom as anthelmintics |
NZ728623A NZ728623A (en) | 2014-08-29 | 2015-08-27 | Novel sulfonylaminobenzamide compounds as anthelmintics |
Publications (2)
Publication Number | Publication Date |
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NZ744117A NZ744117A (en) | 2021-06-25 |
NZ744117B2 true NZ744117B2 (en) | 2021-09-28 |
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