METHOD FOR DUAL INHIBITION OF SGLT1 AND SGLT2 USING DIPHENYLMETHANE DERIVATIVES

摘要

The present invention relates to a method for dual inhibition of sodium-dependent glucose cotransporter 1 (SGLT1) and sodium-dependent glucose cotransporter 2 (SGLT2) present in the intestine and kidney by using the compound of formula I or a pharmaceutically acceptable salt or a prodrug thereof:;;wherein ring A, ring B, X and Y have the same meanings as defined in the specification.

主权项

1. A method for dual inhibition of sodium-dependent glucose cotransporter 1 (SGLT1) and sodium-dependent glucose cotransporter 2 (SGLT2) in a mammal, which comprises administering the compound of formula I or a pharmaceutically acceptable salt or a prodrug thereof to the mammal: wherein, X is oxygen or sulfur; Y is C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C1-7 alkoxy, C1-7 alkoxy-C1-7 alkyl, C1-7 alkylsulfinyl, C1-7 alkylsulfonyl, or C1-7 alkylthio; ring A is said R1a, R1b, R4a, R4b and W being each independently selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, cyano, nitro, amino, carboxy, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C1-7 alkoxy, 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, C1-7 alkylsulfonyl, C6-14 arylsulfanyl, C6-14 arylsulfonyl, C6-14 aryl, 5 to 13-membered heteroaryl, or 5 to 10-membered heterocycloalkyl, said R2 being each independently hydroxy, C1-7 alkyl, or C1-7 alkoxy, said n being an integer of 0 to 3, said Z1, Z2, and Z3 being each independently —CH2—, —CH═, —(CO)—, —O—, —S—, —NH—, or —N═, and said p being an integer of 1 to 3; ring B is with the proviso that when ring A is A-1, then ring B is B-2, wherein, said R5a, R5b, R6a, and R6b being each independently selected from the group consisting of hydrogen, halogen, hydroxy, mercapto, cyano, nitro, amino, carboxy, oxo, C1-7 alkyl, C1-7 alkylthio, C2-7 alkenyl, C2-7 alkynyl, C1-7 alkoxy, C1-7 alkoxy-C1-7 alkyl, C2-7 alkenyl-C1-7 alkyloxy, C2-7 alkynyl-C1-7 alkyloxy, C3-10 cycloalkyl, C3-7 cycloalkylthio, C5-10 cycloalkenyl, C3-10 cycloalkyloxy, C3-10 cycloalkyloxy-C1-7 alkoxy, phenyl-C1-7 alkyl, C1-7 alkylthio-phenyl, phenyl-C1-7 alkoxy, mono- or di-C1-7 alkylamino, mono- or di-C1-7 alkylamino-C1-7 alkyl, C1-7 alkanoyl, C1-7 alkanoylamino, C1-7 alkylcarbonyl, C1-7 alkoxycarbonyl, carbamoyl, mono- or di-C1-7 alkylcarbamoyl, C1-7 alkylsulfonylamino, phenylsulfonylamino, C1-7 alkylsulfinyl, C6-14 arylsulfanyl, C6-14 arylsulfonyl, C6-14 aryl, 5 to 13-membered heteroaryl, 5 to 10-membered heterocycloalkyl, 5 to 10-membered heterocycloalkyl-C1-7 alkyl, or 5 to 10-membered heterocycloalkyl-C1-7 alkoxy, and said ring C being C3-10 cycloalkyl, C5-10 cycloalkenyl, C6-14 aryl, 5 to 13-membered heteroaryl, or 5 to 10-membered heterocycloalkyl; said alkyl, alkenyl, alkynyl, or alkoxy is optionally substituted with at least one substituent selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, mercapto, C1-7 alkyl, and C2-7 alkynyl; and said cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocycloalkyl is optionally substituted with at least one substituent selected from the group consisting of halogen, hydroxy, cyano, nitro, amino, mercapto, C1-4 alkyl, and C1-4 alkoxy.