Elongated and multiple spacers in activatible prodrugs

A - Human Necessities – 61 – K

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A61K 47/48 (2006.01)

Patent

CA 2441597

This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V-(W)k-(X)1-A-Z, wherein: V is a specifier; (W)k-(X)1-A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclisation elimination spacer; Z is a therapeutic drug; k, 1 and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: - when A is (Y)m: k+1+m >= 1, and if k+1+m = 1; - when A is U: k+1 >= 1.

L'invention, porte sur des prodrogues activables au site d'action préféré de manière à délivrer sélectivement le médicament thérapeutique correspondant à des cellules cibles ou à des sites cibles s'adresse principalement mais non exclusivement à des cellules cibles tumorales. Lesdites prodrogues sont plus spécifiquement des composés de formule V-(W)¿k?-(X)¿1?-A-Z, dans laquelle: V est un spécificateur; (W)¿k?-(X)¿1?-A est un système d'espaceurs allongés à autoélimination; W et X sont chacun un espaceur à cascade électronique 1,(4+2n) identique ou différent; A est soit un groupe espaceur de formule (Y)¿m? dans laquelle: Y est un espaceur à cascade électronique 1,(4+2n), ou un groupe de formule U consistant en un espaceur de cyclisation à élimination; Z est un médicament thérapeutique; k, 1 et m sont des entiers de 0 (inclus) à 5 (inclus); n est un entier de 0 (inclus) à 10 (inclus), sous réserve que: quand A est (Y)¿m?: k+1+m, >= 1, et si k+1+m = 1, n>1; quand A est U: k+1 >= 1.

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