NOVEL C-ARYL ANSA SGLT2 INHIBITORS

摘要

Disclosed is a novel C-aryl ansa compound having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney, and a pharmaceutical composition comprising the same as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly diabetes. Also provided are a method for preparing the compound, and a method for preventing or treating metabolic disorders, particularly diabetes, by using the compound.

主权项

1. A compound of formula I, or a pharmaceutically acceptable salt or a prodrug thereof: wherein, X is methylene or cyclopropane; ring A is benzene, naphthalene, or indole; ring B is said ring D being C3-10 cycloalkyl, C5-10 cycloalkenyl, C6-14 aryl, 5 to 13-membered heteroaryl, or 5 to 10-membered heterocycloalkyl; ring C is a macrocycle formed by connecting ansa bridge between the tetrahydropyran ring and ring A; and n is an integer of 5 to 10, wherein, said ring A and ring B are each independently optionally substituted with at least one selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, cyano, nitro, amino, carboxy, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, hydroxy-C1-7 alkyl, C1-7alkoxy, C1-7 alkoxy-C1-7 alkyl, C2-7 alkenyl-C1-7 alkyloxy, C2-7 alkynyl-C1-7 alkyloxy, C3-10 cycloalkyl, C5-10 cycloalkenyl, C3-10 cycloalkyloxy, phenyl-C1-7 alkoxy, mono- or di-C1-7 alkylamino, C1-7 alkanoyl, C1-7 alkanoylamino, C1-7 alkoxycarbonyl, carbamoyl, mono- or di-C1-7 alkylcarbamoyl, C1-7 alkylsulfonylamino, phenylsulfonylamino, C1-7 alkylsulfanyl, C1-7 alkylsulfinyl, alkylsulfonyl, C6-14 arylsulfanyl, C6-14 arylsulfonyl, C6-14 aryl, 5 to 13-membered heteroaryl, and 5 to 10-membered heterocycloalkyl; said R5a, R5b, R6a, and R6b are each independently selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, cyano, nitro, amino, carboxy, alkyl, C2-7 alkenyl, C2-7 alkynyl, hydroxy-C1-7 alkyl, C1-7alkoxy, C1-7alkoxy-C1-7 alkyl, C2-7 alkenyl C1-7 alkyloxy, C2-7 alkynyl-C1-7 alkyloxy, C3-10 cycloalkyl, C5-10 cycloalkenyl, C3-10 cycloalkyloxy, phenyl-C1-7 alkoxy, mono- or di-C1-7 alkylamino, alkanoyl, C1-7 alkanoylamino, alkoxycarbonyl, carbamoyl, mono- or di-C1-7 alkylcarbamoyl, alkylsulfonylamino, phenylsulfonylamino, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, C6-14 arylsulfanyl, C6-14 arylsulfonyl, C6-14 aryl, 5 to 13-membered heteroaryl, and 5 to 10-membered heterocycloalkyl; said alkyl, alkenyl, alkynyl, or alkoxy is optionally substituted with at least one selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, mercapto, C1-7alkyl, and C2-7 alkynyl; and said cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocycloalkyl is optionally substituted with at least one selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, mercapto, C1-4 alkyl, and C1-4 alkoxy.