4-(2-furoyl) aminopiperidines, intermediates in synthesizing...

C - Chemistry – Metallurgy – 07 – D

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C07D 405/14 (2006.01) A61K 31/443 (2006.01) A61K 31/4525 (2006.01) A61K 31/453 (2006.01) A61K 31/454 (2006.01) A61K 31/4545 (2006.01) A61K 31/497 (2006.01) A61K 31/5377 (2006.01) A61P 1/04 (2006.01) A61P 1/08 (2006.01) A61P 1/10 (2006.01) A61P 17/04 (2006.01) A61P 43/00 (2006.01) C07D 211/58 (2006.01) C07D 401/12 (2006.01) C07D 405/12 (2006.01) C07D 413/14 (2006.01)

Patent

CA 2468529

There are provided novel 4-(2-furoyl)aminopiperidines represented by the general formula (I), their synthetic intermediates, processes for their preparation and medicaments containing them. (see formula I) In the above formula, X is CH or N, and Y is a group of the following general formula (II), formula (II-a) or formula (III): (see formula II) (see formula II-a) (see formula III) wherein a, b and c are each an integer of 0-6; Z is CH2 or NH; W is O or S; T is O or N-R15 wherein R15 is H, a C1-C6 alkyl group, a benzyl group or a phenethyl group; and R1 is H, a C1-C6 alkoxycarbonyl group, a benzyloxycarbonyl group, or the like. The 4-(2-furoyl) aminopiperidine derivatives according to this invention possess opioid µ antagonistic activity and are useful for the treatment or prevention of side effects which are caused by µ receptors agonist and which are selected from constipation, nausea/emesis or itch, or for the treatment or prevention of idiopathic constipation, postoperative ileus, paralytic ileus, irritable bowel syndrome or chronic pruritus.

La présente invention concerne de nouvelles 4-(2-furoyl)aminopipéridines représentées par la formule générale (I), des intermédiaires utilisés dans la synthèse de ces dernières, leur procédé de production et des médicaments les contenant en tant que principe actif. Dans la formule (I), X représente CH ou N ; et Y représente un groupe représenté par la formule générale suivante (II), (II-a) ou (III) dans lesquelles a, b et c représentent chacun un entier compris entre 0 et 6 ; Z représente CH¿2? ou NH ; W représente O ou S ; T représente O ou N-R?15¿ (où R?15¿ représente H, alkyle C¿1-6?, benzyle ou phénéthyle) ; et R?1¿ représente H, alcoxycarbonyle C¿1-6?, benzyloxycarbonyle, etc. Du fait de leur antagonisme à l'opioïde µ, ces dérivés de 4-(2-furoyl)aminopipéridines sont utiles dans la prévention ou le traitement d'effets secondaires des agonistes du récepteur d'opioïde µ sélectionnés parmi la constipation, la nausée, le vomissement et l'eczéma, la constipation soudaine, l'iléus postopératoire, l'iléus paralytique, le syndrome du côlon irritable ou l'eczéma chronique.

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