Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-05-09
1995-12-12
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546271, 5483087, 548159, 548181, 548207, 548209, 548241, 5483091, 514367, 514370, 514373, 514379, 514395, A61K 3147, A61K 31415, C07D40104, C07D23504
Patent
active
054750059
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP92/02564 filed Nov. 4, 1992.
The present invention related to certain benzimidazole anthelmintic agents which, quite unexpectedly, are topically and parenterally active and are thus suitable for transdermal and parenteral (especially intramuscular) administration.
These benzimidazole derivatives are represented by the formula: ##STR1## and their non-toxic salts, wherein R.sup.1, which is in the 5(6)-position, is either (i) H, benzoyl, phenyloxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylsulfonyloxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 alkylsulfonyl or (C.sub.3 -C.sub.7 cycloalkyl) carbonyl, said phenyl groups, and the phenyl portion of said benzoyl group, optionally having 1 to 3 substituents each independently selected from halo, C.sub.1 -C.sub.4 alkyl, halo-(C.sub.1 -C.sub.4 alkyl), C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulfinyl, C.sub.1 -C.sub.4 alkylsulfonyl, C.sub.2 -C.sub.4 alkanoyl, nitro, isothiocyanato, and cyano; or (ii) a group of the formula: ##STR2## where X is O,S,SO,SO.sub.2 or NR.sup.4 in which R.sub.4 is hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl or phenyl-(C.sub.1 -C.sub.4 alkyl), wherein said phenyl and the phenyl portion of said phenyl-(C.sub.1 -C.sub.4) alkyl) groups are optionally substituted by 1 or 2 substituents each selected from C.sub.1 -C.sub.4 alkyl, halo, hydroxy and C.sub.1 -C.sub.4 alkoxy; and R.sub.5 is H, C.sub.1 -C.sub.4 alkyl, halo, hydroxy or C.sub.1 -C.sub.4 alkoxy; ##STR3## "alk" is a methylene or ethylene group; R.sup.2 is cyano, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, C.sub.2 -C.sub.4 alkanoyl, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.4 alkenoxy, aryl, heteroaryl, aryl-(C.sub.1 -C.sub.4 alkoxy) or heteroaryl-(C.sub.1 -C.sub.4 alkoxy), in which "aryl" means phenyl optionally substituted by 1 to 3 substituents each independently selected from halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphinyl and C.sub.1 -C.sub.4 alkylsulphonyl, and in which "heteroaryl" means thienyl, furyl or pyridinyl all optionally substituted by 1 to 3 substituents each independently selected from halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphinyl and C.sub.1 -C.sub.4 alkylsulphonyl; and R.sub.3 is a C.sub.1 -C.sub.4 alkyl group.
Preferred alkyl and alkoxy groups have 1 to 4 carbon atoms.
R.sup.1 is preferably H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphinyl, phenylthio, phenylsulfinyl, benzoyl optionally substituted by halo, phenylsulfonyloxy optionally substituted by halo, or 1,2-benzisoxazol-3-yl.
More preferably, R.sup.1 is H, benzoyl, 4-fluorobenzoyl, 4-fluorophenylsulfonyloxy, n-propylthio, n-propylsulfinyl, phenylthio, phenylsulfinyl, n-butyl, n-propyloxy, or 1,2-benzisoxazol-3-yl.
Most preferably, R.sup.1 is n-propylthio;
"alk" is preferably methylene.
R.sup.2 is preferably methoxy, ethoxy, allyloxy, benzyloxy, phenyl optionally substituted by 1 to 3 methoxy substituents, cyano, ethynyl, vinyl or acetyl.
R.sup.3 is preferably methyl.
Alkyl, alkoxy, alkenyl and alkynyl groups, when appropriate, can be straight or branched chain. "Halo" means F, Cl, Br or I.
Suitable non-toxic acid addition salts, suitable for veterinary use, are for example the hydrochloride, hydrobromide, and sulphate salts. These can all be prepared conventionally.
The benzimidazoles of the formula (I) and their salts are in particular anthelmintics suitable for the control of parasitic diseases in both human and non-human animals such as sheep and cattle and domestic pets. The compounds exhibit activity against mature and immature parasitic forms of, for example, nematodes, trematodes and cestodes such as are represented by Trichostrongylus, Dictyocaulus, Ostertagia, Nematodirus, Stronglyoides, Trichuris, Haemonchus, Cooperia, Dirofilaria, Toxocara, Trichur
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Banks Bernard J.
Dutton Christopher J.
Goudie Alexander C.
Creagan B. Timothy
Holtrust Gezina
Pfizer Inc.
Richardson Peter C.
Richter Johann
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