N1-cyclic amine-N5-substituted phenyl biguanide derivatives, methods of preparing the same and pharmaceutical composition comprising the same

摘要

An N1-cyclic amine-N5-substituted phenyl biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs. Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

主权项

1. A compound of Formula 1 or a pharmaceutically acceptable salt thereof: wherein R1 and R2 are taken together with nitrogen to which they are attached to form 3- to 8-membered heterocycloalkyl, wherein the heterocycloalkyl is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen, hydroxy and C1-6alkyl; n is an integer ranging from 2 to 5; each R3 is unsubstituted or substituted and is independently selected from the group consisting of halogen, unsubstituted hydroxy, substituted C1-6alkyl, unsubstituted or substituted C1-6alkoxy, unsubstituted or substituted C1-6alkylthio, unsubstituted or substituted amino, unsubstituted or substituted amide, unsubstituted or substituted sulfonamide, nitro, unsubstituted or substituted heteroaryl, cyano, sulfonic acid and unsubstituted or substituted sulfamoyl, wherein the substituted R3 has at least one substituent selected from the group consisting of halogen, hydroxy and C1-6alkyl.