Diphenylmethane derivatives as SGLT2 inhibitors
First Claim
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1. A compound of formula I, or a pharmaceutically acceptable salt or a prodrug thereof:
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Abstract
A compound with a diphenylmethane moiety having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney is disclosed. A pharmaceutical composition including the compound as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly diabetes is disclosed. A method for preparing the compound, and a method for preventing or treating metabolic disorders, particularly diabetes, by using the compound is provided.
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Citations
12 Claims
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1. A compound of formula I, or a pharmaceutically acceptable salt or a prodrug thereof:
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2. The compound of claim 1, wherein said ring A-2 is selected from the group consisting of:
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3. The compound of claim 1, wherein said ring B-1 is selected from the group consisting of:
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4. The compound of claim 1, wherein said ring B-2 is selected from the group consisting of:
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5. The compound of claim 1, wherein said ring A is a dihydrobenzofuran, dihydroisobenzofuran, benzofuran, dihydrobenzothiophene, benzothiophene, chroman, chromene, isochroman, isochromene, benzodioxole, benzodioxane, benzooxazine, tetrahydroquinoline, tetrahydroquinoxaline, tetrahydroisoquinoline, indazole, indole, indoline, benzoimidazole, benzooxazole, benzothiazole, benzotriazole, quinazoline, quinoxaline, cinnoline, phthalazine, or benzotriazine ring, which is optionally substituted with a substituent as defined in claim 1.
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6. The compound of claim 1, wherein said ring B is a quinoline, quinoxaline, 3,4-dihydro-2H-benzo[b][1,4]dioxepine, 2,3-dihydrobenzo[b]thiophene, indazole, indole, 2,3-dihydrobenzo[b][1,4]dioxine, benzodioxole, indane, tetrahydronaphthalene, 3,4-dihydro-2H-thiochromene, dihydrobenzofuran, benzo[d][1,3]oxathiole, tetrahydroquinoline, or 3,4-dihydro-2H-benzo[b][1,4]oxazine ring, which is optionally substituted with a substituent as defined in claim 1.
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7. The compound of claim 1, which is selected from the group consisting of:
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(1) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (2) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (3) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-ethoxybenzyl)chroman-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (4) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-ethoxybenzyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (5) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-methoxybenzyl)chroman-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (6) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-ethylbenzyl)chroman-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (7) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-methoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (8) (2S,3R,4R,5S,6R)-2-(6-(4-ethylbenzyl)-7-chloro-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (9) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (10) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (11) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-ethylbenzyl)chroman-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (12) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (13) (2S,3R,4R,5S,6R)-2-(5-chloro-6-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)chroman-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (14) (2S,3R,4R,5S,6R)-2-(7-chloro-6-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (15) (2S,3R,4R,5S,6R)-2-(8-chloro-7-((2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (16) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-methoxybenzyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (17) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-ethylbenzyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (18) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-vinylbenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (19) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-cyclopropylbenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (20) ((2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-cyclopropylbenzyl)chroman-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (21) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-(trifluoromethyl)benzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (22) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-chlorobenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (23) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(trifluoromethyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (24) (2S,3R,4S,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-methyltetrahydro-2H-pyran-3,4,5-triol; (25) (2S,3R,4R,5S,6S)-2-(7-chloro-6-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(fluoromethyl)tetrahydro-2H-pyran-3,4,5-triol; (26) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(1-hydroxyethyl)tetrahydro-2H-pyran-3,4,5-triol; (27) (2S,3R,4R,5S,6S)-2-(7-chloro-6-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(difluoromethyl)tetrahydro-2H-pyran-3,4,5-triol; (28) (2S,3R,4R,5S,6R)-2-(6-(4-ethoxybenzyl)-7-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (29) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-methoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (30) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (31) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (32) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-cyclopropylbenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (33) (2S,3R,4R,5S,6R)-2-(4-chloro-2-methyl-5-(4-propylbenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (34) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (35) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethylbenzyl)-2-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (36) (2S,3R,4R,5S,6R)-2-(7-chloro-2-methyl-6-(4-vinylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (37) ((2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-cyclopropylbenzyl)-2-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (38) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(methylamino)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol 2,2,2-trifluoroacetate (39) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-2-methyl-2,3-dihydrobenzo[b]thiophen-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (40) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzo[b]thiophen-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (41) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-2-methyl-2,3-dihydrobenzo[b]thiophen-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (42) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; (43) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(methylsulfonyl)tetrahydro-2H-pyran-3,4,5-triol; (44) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-((S)-methylsulfinyl)tetrahydro-2H-pyran-3,4,5-triol; (45) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-ethoxybenzyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; (46) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-isopropylbenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (47) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-isopropylbenzyl)-2-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (48) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-(methylthio)benzyl)chroman-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (49) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-cyclopropylbenzyl)chroman-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (50) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-methoxybenzyl)chroman-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (51) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-ethoxybenzyl)chroman-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (52) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-cyclopropylbenzyl)benzo[d][1,3]dioxol-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (53) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-isopropylbenzyl)benzo[d][1,3]dioxol-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (54) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)benzo[d][1,3]dioxol-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (55) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-methoxybenzyl)benzo[d][1,3]dioxol-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (56) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethylbenzyl)benzo[d][1,3]dioxol-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (57) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-cyclopropylbenzyl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (58) (2S,3R,4R,5S,6R)-2-(9-chloro-8-(4-ethoxybenzyl)-3,4-dihydro-2H-benzo[b][1,4]dioxepin-6-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (59) (2S,3R,4R,5S,6R)-2-(9-chloro-8-(4-ethylbenzyl)-3,4-dihydro-2H-benzo[b][1,4]dioxepin-6-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (60) (2S,3R,4R,5S,6R)-2-(6-benzyl-7-chloro-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (61) 1-(4-((7-chloro-4-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2,3-dihydrobenzofuran-6-yl)methyl)phenyl)ethanone; (62) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(1-hydroxyethyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (63) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(1-fluoroethyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (64) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-vinylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (65) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-cyclopropylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (66) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-cyclopropylbenzyl)benzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (67) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(2-hydroxypropan-2-yl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (68) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(difluoromethyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (69) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(1,1-difluoroethyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (70) (2S,3R,4R,5S,6R)-2-(6-(4-cyclopropylbenzyl)-7-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (71) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(2-hydroxybut-3-yn-2-yl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (72) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(prop-1-en-2-yl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (73) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-isopropylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (74) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethynylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (75) 4-((7-chloro-4-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2,3-dihydrobenzofuran-6-yl)methyl)benzonitrile; (76) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-propylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (77) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-methoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-thiopyran-3,4,5-triol; (78) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(methylthio)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (79) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(dimethylamino)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (80) (2S,3R,4R,5S,6R)-2-(4-chloro-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (81) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-hydroxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (82) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(3-hydroxypropoxyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (83) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-propoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (84) 4-chloro-5-(4-methoxybenzyl)-7-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)benzofuran-3(2H)-one; (85) (2S,3R,4R,5S,6R)-2-(4-chloro-3-hydroxy-5-(4-methoxybenzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (86) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-(dimethylamino)benzyl)-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (87) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(2-cyclopropoxyethoxyl)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (88) (2S,3R,4R,5S,6R)-2-(6-(4-(azetidin-1-yl)benzyl)-7-chloro-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (89) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(trifluoromethoxy)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (90) 2-(4-((7-chloro-4-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-2,3-dihydrobenzofuran-6-yl)methyl)phenyl)acetonitrile; (91) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(oxetan-3-yloxy)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (92) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-isopropoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (93) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(cyclopropylthio)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (94) (2S,3R,4R,5S,6R)-2-(7-chloro-6-((5-methoxythiophen-2-yl)methyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (95) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-methoxybenzyl)chroman-8-yl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; (96) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-2,3-dihydrobenzo[b]thiophen-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (97) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-ethoxybenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (98) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-ethoxybenzyl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (99) (2S,3R,4R,5S,6R)-2-(5-chloro-6-(4-ethylbenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (100) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-3-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (101) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-3-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (102) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethylbenzyl)-3,3-dimethyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (103) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-3,3-dimethyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (104) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-methoxybenzyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (105) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (106) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-3-methyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (107) (2S,3R,4R,5S,6R)-2-(4-chloro-5-(4-ethoxybenzyl)-3,3-dimethyl-2,3-dihydrobenzofuran-7-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (108) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-3-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (109) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-3,3-dimethyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (110) 7-chloro-6-(4-ethoxybenzyl)-4-(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yl)benzofuran-3(2H)-one (111) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-ethoxybenzyl)-3-methoxy-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (112) (2S,3R,4R,5S,6R)-2-(7-cyclopropyl-6-(4-ethoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (113) (2S,3R,4R,5S,6R)-2-(6-(4-ethoxybenzyl)-7-propyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (114) (2S,3R,4R,5S,6R)-2-(7-chloro-6-((1,2,3,4-tetrahydroquinolin-7-yl)methyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (115) (2S,3R,4R,5S,6R)-2-(7-chloro-6-((3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (116) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-(cyclopentyloxy)benzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (117) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-cyclopentylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (118) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-cyclobutoxybenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (119) (2S,3R,4R,5S,6R)-2-(6-(4-tert-butylbenzyl)-7-chloro-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (120) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-cyclobutylbenzyl)-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol; (121) (2S,3R,4R,5S,6R)-2-(7-(difluoromethyl)-6-(4-methoxybenzyl)-2,3-dihydro-1H-inden-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (122) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-methoxybenzyl)-2,3-dihydrobenzo[b]thiophen-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (123) (2S,3R,4R,5S,6R)-2-(8-chloro-7-(4-methoxybenzyl)thiochroman-5-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; (124) (2S,3R,4R,5S,6R)-2-(4-chloro-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-2-methoxyphenyl)-6-(hydroxymethyl)tetrahydro-2H-thiopyran-3,4,5-triol; and (125) (2S,3R,4R,5S,6R)-2-(7-chloro-6-(4-isopropylbenzyl)-2-methyl-2,3-dihydrobenzofuran-4-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol.
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8. A method for preparing a compound of formula I-a, comprising:
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a) reacting a compound of formula II with a compound of formula III to obtain a compound of formula IV; and (b) deprotecting and reducing the compound of formula IV to obtain a compound of formula I-a,
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9. The method of claim 8, wherein step (b) is carried out by deprotecting the compound of formula IV to obtain a compound of formula V, and reducing the compound of formula V to obtain the compound of formula I-a, when PG is trimethylsilyl:
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10. The method of claim 8, wherein step (b) is carried out by reducing the compound of formula IV to obtain a compound of formula VI, and deprotecting the compound of formula VI to obtain the compound of formula I-a, when PG is benzyl:
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11. A pharmaceutical composition, comprising as an active ingredient the compound of formula I of claim 1 or a pharmaceutically acceptable salt or a prodrug thereof, and a pharmaceutically acceptable carrier.
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12. A method for treating a diabetes in a mammal, which comprises administering the compound of formula I of claim 1 or a pharmaceutically acceptable salt or a prodrug thereof to the mammal.
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2. The compound of claim 1, wherein said ring A-2 is selected from the group consisting of:
Specification
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Current AssigneeGreen Cross Corporation (Green Cross Holdings Corporation)
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Original AssigneeGreen Cross Corporation (Green Cross Holdings Corporation)
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InventorsChoi, Soongyu, Song, Kwang Seop, Lee, Suk Ho, Kim, Min Ju, Seo, Hee Jeong, Park, Eun-Jung, Kong, Younggyu, Park, So Ok, Kang, Hyunku, Jung, Myung Eun, Lee, Kinam, Kim, Hyun Jung, Lee, Jun Sung, Lee, Min Woo, Kim, Mi-Soon, Hong, Dong Ho, Kang, Misuk
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Primary Examiner(s)SHAMEEM, GOLAM M
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Application NumberUS14/122,836Publication NumberTime in Patent Office1,082 DaysField of Search549/356, 549/414, 514/451, 514/460US Class Current514/460CPC Class CodesA61P 3/00 Drugs for disorders of the ...A61P 3/10 for hyperglycaemia, e.g. an...A61P 43/00 Drugs for specific purposes...C07D 309/10 Oxygen atomsC07D 405/10 linked by a carbon chain co...C07D 405/14 containing three or more he...C07D 407/04 directly linked by a ring-m...C07D 407/10 linked by a carbon chain co...C07D 407/14 containing three or more he...C07D 409/04 directly linked by a ring-m...C07D 409/10 linked by a carbon chain co...C07D 409/14 containing three or more he...C07D 411/10 linked by a carbon chain co...C07D 413/04 directly linked by a ring-m...C07D 413/10 linked by a carbon chain co...C07D 413/12 linked by a chain containin...C07D 413/14 containing three or more he...