New benzimidazole compounds for use as active therapeutic...

C - Chemistry – Metallurgy – 07 – D

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C07D 403/12 (2006.01) A61K 31/505 (2006.01) C07D 417/12 (2006.01)

Patent

CA 2359107

The present invention relates to new benzimidazole compounds with general structure (I): in which Y-X is ~C = X when X is NR8, O, or S and R2 is H, alkyl, substituted alkylaryl or substituted aryl; or Y-X is ~C-X when X is H, alkyl, substituted alkyl, aryl, substituted aryl, OR9 or NHR9 and R2 is a bond to Y; Z = O, S or NR12; R1 is H, alkyl, substituted alkyl, aryl or substituted aryl; R3 is H, alkyl, substituted alkyl, aryl or substituted aryl, OR9 or NHR9; R4, R5, R6, R7 are H, halogen, OR10, NR10, R11, NO2, CF3, CN, COR8, COOR8, CONHR8 and/or N3 in any combination and/or two adjacent R4, R5, R6 or R7 form a carbocyclic or heterocyclic ring; R8, R9, R10, R11, R12 and R13 are H, alkyl, substituted alkylaryl, aryl and/or substituted aryl in any combination. These compounds are useful as a human Growth Hormone (hGH) mimetic, which trigger GH agonist effects in animals and especially as an orally availabel human Growth Hormone (hGH).

L'invention concerne de nouveaux composés de benzimidazole de structure générale (I), dans laquelle Y-X est > C=X quand X est NR8, O ou S et R2 est H, alkyle, alkylaryle substitué ou aryle substitué; ou bien Y-X est > C-X quand X est H, alkyle, alkyle substitué, aryle, aryle substitué, OR9 ou NHR9 et R2 est une liaison avec Y; Z = O, S ou NR12; R1 est H, alkyle, alkyle substitué, aryle or aryle substitué; R3 est H, alkyle, alkyle substitué, aryle ou aryle substitué, OR9 ou NHR9; R4, R5, R6, R7 sont H, halogène, OR10, NR10, R11, NO¿2?, CF¿3?, CN, COR8, COOR8, CONHR8 et/ou N¿3? dans n'importe quelle combinaison et/ou deux R4, R5, R6 ou R7 adjacents forment un noyau carbocyclique or hétérocyclique; et R8, R9, R10, R11, R12 et R13 sont H, alkyle, alkylaryle substitué, aryle et/ou aryle substitué dans n'importe quelle combinaison. Ces composés, utiles comme mimétiques de l'hormone de croissance humaine (hGH), déclenchent des effets agonistes de GH chez l'animal. Ils peuvent donc notamment être utilisés chez l'homme comme hormone de croissance à administration orale (hGH).

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