INHIBITORS OF SODIUM GLUCOSE COTRANSPORTER 1

摘要

Inhibitors of sodium glucose cotransporter 1 (SGLT1), compositions comprising them, and methods of their use to treat diseases and disorders such as diabetes are disclosed. Particular compounds are of the formula:;;the various substituents of which are defined herein.

主权项

1. A compound of the formula:or a pharmaceutically acceptable salt, dimer or trimer thereof, wherein:
R1 is hydrogen or optionally substituted C1-10-alkyl, C1-5-cycloalkyl, or 5-membered heterocycle, which optional substitution is with one or more R1A; each R1A is independently amino, ester, amide, thiol, carboxylic acid, cyano, halo, hydroxyl, or optionally substituted C1-4-alkoxy, C1-5-cycloalkyl, or 5-membered heterocycle, which optional substitution is with one or more R1B; each R1B is independently C1-4-alkyl, halo, or hydroxyl; n is 0, 1, or 2; each R2 is independently F or OR2A, wherein each R2A is independently hydrogen, C1-4-alkyl, or acyl; each R3 is independently halo, hydroxyl, or optionally substituted C1-10-alkyl or C1-10-alkoxy, which optional substitution is with one or more R3A; each R3A is independently amino, ester, amide, thiol, carboxylic acid, cyano, halo, hydroxyl, or optionally substituted C1-4-alkoxy, C1-5-cycloalkyl, or 5-membered heterocycle, which optional substitution is with one or more R3B; each R3B is independently C1-4-alkyl, amino, cyano, halo, or hydroxyl; p is 0, 1, or 2; each R4 is independently R4A, —N(R4A)(R4B), —OR4A, —SR4A, —S(O)R4A, or —S(O)2R4A; R4A is optionally substituted C4-20-alkyl or 4-20-membered heteroalkyl, which optional substitution is with one or more R4C, and which is optionally attached to another R4A moiety to provide a dimer or trimer; R4B is hydrogen or R4A; each R4C is independently amino, amido, azo, carbonyl, carboxyl, cyano, formyl, guanidino, halo, hydroxyl, imido, imino, isothiocyanate, nitrile, nitro, nitroso, nitroxy, oxo, sulfanyl, sulfinyl, sulfonyl, thial, thiocyanate, thione, thiourea, urea, or X1, X1-L1-X2, or X1-L1-X2-L2-X3, wherein each of X1, X2 and X3 is independently optionally substituted C1-4-alkyl, C1-6-cycloalkyl, 5- or 6-membered heterocycle, or aryl, which optional substitution is with one or more R4D, and each of L1 and L2 is independently optionally substituted C1-6-alkyl or 1-10-membered heteroalkyl, which optional substitution is with one or more of R4E; each R4D is independently R4E or C1-6-alkyl optionally substituted with one or more of R4E; each R4E is independently amino, amido, azo, carbonyl, carboxyl, cyano, formyl, guanidino, halo, hydroxyl, imido, imino, isothiocyanate, nitrile, nitro, nitroso, nitroxy, oxo, sulfanyl, sulfinyl, sulfonyl, thial, thiocyanate, thione, or urea; and m is 1, 2 or 3.