Granted Patent B2

US 7,838,499 · App. 12/197,095 · Granted Nov 23, 2010

Assignee: Theracos, Inc.

Abstract

Claims (90)

1. A compound of Formula I:

wherein

V is a member selected from the group consisting of oxygen; sulfur; SO; SO 2 ; and a single bond;

W is a member selected from the group consisting of C 1 -C 6 alkylene, C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, C 3 -C 10 cycloalkylene, C 5 -C 10 cycloalkenylene and (C 3 -C 10 cycloalkylene)(C 1 -C 6 alkylene) wherein the C 3 -C 10 cycloalkylene portion bonds to V and the C 1 -C 6 alkylene portion bonds to X, and

wherein alkylene, alkenylene, alkynylene, cycloalkylene and cycloalkenylene groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by substituents independently selected from the group consisting of chlorine, hydroxy, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyloxy, C 5 -C 10 cycloalkenyl and C 5 -C 10 cycloalkenyloxy, and in cycloalkylene and cycloalkenylene groups or portions one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO 2 or NR b , and one or two methyne groups are optionally replaced by N;

X is a member selected from the group consisting of oxygen; sulfur; SO; and SO 2 ;

Y is a member selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 5 -C 10 cycloalkenyl, (C 3 -C 10 cycloalkyl)C 1 -C 4 alkyl, (C 5 -C 10 cycloalkenyl)C 1 -C 3 alkyl, (C 3 -C 10 cycloalkyl)C 2 -C 4 alkenyl, C 3 -C 6 cycloalkylidenmethyl, (C 5 -C 10 cycloalkenyl)C 2 -C 4 alkenyl, (C 1 -C 4 alkyloxy)C 1 -C 3 alkyl, (C 2 -C 4 alkenyloxy)C 1 -C 3 alkyl, (C 3 -C 10 cycloalkyloxy)C 1 -C 3 alkyl, (C 5 -C 10 cycloalkenyloxy)C 1 -C 3 alkyl, (amino)C 1 -C 3 alkyl, (C 1 -C 4 alkylamino)C 1 -C 3 alkyl, di-(C 1 -C 3 alkylamino)C 1 -C 3 alkyl, (C 1 -C 6 alkyl)carbonyl(C 1 -C 3 )alkyl, (C 2 -C 6 alkenyl)carbonyl(C 1 -C 3 )alkyl, (C 2 -C 6 alkynyl)carbonyl(C 1 -C 3 )alkyl, (arylcarbonyl)C 1 -C 3 alkyl, (heteroarylcarbonyl)C 1 -C 3 alkyl, (C 1 -C 6 alkylsulfonyl)C 1 -C 3 alkyl, (C 2 -C 6 alkenylsulfonyl)C 1 -C 3 alkyl, (C 2 -C 6 alkynylsulfonyl)C 1 -C 3 alkyl, (arylsulfonyl)C 1 -C 3 alkyl, (heteroarylsulfonyl)C 1 -C 3 alkyl, (C 1 -C 6 alkyl)aminocarbonyl(C 1 -C 3 )alkyl, (C 2 -C 6 alkenyl)aminocarbonyl(C 1 -C 3 )alkyl, (C 2 -C 6 alkynyl)aminocarbonyl(C 1 -C 3 )alkyl, (arylaminocarbonyl)C 1 -C 3 alkyl, (heteroarylaminocarbonyl)C 1 -C 3 alkyl, (C 1 -C 6 alkyl)carbonyl, (C 2 -C 6 alkenyl)carbonyl, (C 2 -C 6 alkynyl)carbonyl, arylcarbonyl, heteroarylcarbonyl, (C 1 -C 6 alkyl)sulfonyl, (C 2 -C 6 alkenyl)sulfonyl, (C 2 -C 6 alkynyl)sulfonyl, arylsulfonyl and heteroarylsulfonyl;

wherein alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by substituents independently selected from the group consisting of chlorine, hydroxy, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyloxy, C 5 -C 10 cycloalkenyl, C 5 -C 10 cycloalkenyloxy, and NR b R c , and in cycloalkyl and cycloalkenyl groups or portions one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO 2 or NR b , and one or two methyne groups are optionally replaced by N, wherein the heterocycle formed by said optional replacement is other than heteroaryl, and wherein

when V is a member selected from the group consisting of oxygen, sulfur and a single bond and W is C 1 -C 6 alkylene, then Y is other than hydrogen or C 1 -C 6 alkyl; and

when V is oxygen, W is C 3 -C 10 cycloalkylene and X is oxygen, then Y is other than hydrogen, C 1 -C 6 alkyl or trifluoromethyl; and

when V is a single bond and W is a member selected from the group consisting of C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, C 3 -C 10 cycloalkylene and C 5 -C 10 cycloalkenylene, then Y is other than hydrogen, C 1 -C 6 alkyl or (C 3 -C 10 cycloalkyl)C 1 -C 4 alkyl; and

when V is a member selected from the group consisting of oxygen, sulfur, SO and SO 2 , W is a member selected from the group consisting of C 2 -C 6 alkenylene and C 2 -C 6 alkynylene, and Y is a member selected from the group consisting of C 3 -C 10 cycloalkyl and C 5 -C 10 cycloalkenyl, then X can also represent a single bond;

or optionally, X is NR a and Y is a member selected from the group consisting of C 1 -C 6 alkylsulfonyl, C 2 -C 6 alkenylsulfonyl, C 2 -C 6 alkynylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C 1 -C 6 alkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, (C 1 -C 6 alkyl)carbonyl, (C 2 -C 6 alkenyl)carbonyl, (C 2 -C 6 alkynyl)carbonyl, arylcarbonyl, heteroarylcarbonyl, (C 1 -C 6 alkyl)aminocarbonyl, (C 2 -C 6 alkenyl)aminocarbonyl, (C 2 -C 6 alkynyl)aminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, (C 1 -C 6 alkylsulfonyl)C 1 -C 3 alkyl, (C 2 -C 6 alkenylsulfonyl)C 1 -C 3 alkyl, (C 2 -C 6 alkynylsulfonyl)C 1 -C 3 alkyl, (arylsulfonyl)C 1 -C 3 alkyl, (heteroarylsulfonyl)C 1 -C 3 alkyl, (C 1 -C 6 alkylsulfinyl)C 1 -C 3 alkyl, (arylsulfinyl)C 1 -C 3 alkyl, (heteroarylsulfinyl)C 1 -C 3 alkyl, (C 1 -C 6 alkyl)aminocarbonyl(C 1 -C 3 )alkyl, (C 2 -C 6 alkenyl)amino carbonyl(C 1 -C 3 )alkyl, (C 2 -C 6 alkynyl)aminocarbonyl(C 1 -C 3 )alkyl, (arylaminocarbonyl)C 1 -C 3 alkyl and (heteroarylaminocarbonyl)C 1 -C 3 alkyl;

wherein alkyl, alkenyl and alkynyl portions are optionally partly or completely fluorinated, and

when R a is a member selected from the group consisting of H and (C 1 -C 4 alkyl)carbonyl, then Y is other than (C 1 -C 6 alkyl)carbonyl or arylcarbonyl;

Z is a member selected from the group consisting of oxygen; sulfur; SO; SO 2 ; 1,1-cyclopropylene; carbonyl; and methylene optionally substituted with one to two substituents independently selected from halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl and C 3 -C 6 cycloalkyloxy;

R 1 , R 2 and R 3 are each members independently selected from the group consisting of hydrogen, halo, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 5 -C 10 cycloalkenyl, C 1 -C 6 alkyloxy, C 3 -C 10 cycloalkyloxy, cyano and nitro, wherein alkyl and cycloalkyl groups or portions are optionally mono- or polysubstituted by fluorine, or

when R 1 and R 2 are bound to two adjacent C atoms, R 1 and R 2 are optionally joined together to form a C 3 -C 5 alkylene, C 3 -C 5 alkenylene or butadienylene bridge, which is optionally partly or completely fluorinated and is optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C 1 -C 3 alkoxy and C 1 -C 3 alkyl, and wherein one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO 2 or NR b , and wherein one or two methyne groups are optionally replaced by N;

R 4 and R 5 are each members independently selected from the group consisting of hydrogen, halo, cyano, nitro, hydroxy, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, C 1 -C 3 alkyloxy and C 3 -C 10 cycloalkyloxy, wherein alkyl and cycloalkyl groups or portions are optionally mono- or polysubstituted by fluorine, or

when R 4 and R 5 are bound to two adjacent C atoms, R 4 and R 5 are optionally joined together to form a C 3 -C 5 alkylene, C 3 -C 5 alkenylene or butadienylene bridge, which is optionally partly or completely fluorinated and is optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C 1 -C 3 alkoxy and C 1 -C 3 alkyl, and wherein one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO 2 or NR b , and wherein one or two methyne groups are optionally replaced by N;

R 6 , R 7 , R 8 and R 9 are each members independently selected from the group consisting of hydroxy, (C 1 -C 18 alkyl)carbonyloxy, (C 1 -C 18 alkyl)oxycarbonyloxy, arylcarbonyloxy, aryl-(C 1 -C 3 alkyl)carbonyloxy, (C 3 -C 10 cycloalkyl)carbonyloxy, hydrogen, halo, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (C 3 -C 10 )cycloalkyl-(C 1 -C 3 )alkyl, (C 5 -C 7 )cycloalkenyl-(C 1 -C 3 )alkyl, aryl-(C 1 -C 3 )alkyl, heteroaryl-(C 1 -C 3 )alkyl, C 1 -C 6 alkyloxy, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyloxy, C 3 -C 7 cycloalkyloxy, C 5 -C 7 cycloalkenyloxy, aryloxy, heteroaryloxy, (C 3 -C 7 )cycloalkyl-(C 1 -C 3 )alkyloxy, (C 5 -C 7 )cycloalkenyl-(C 1 -C 3 )alkyloxy, aryl-(C 1 -C 3 )alkyloxy, heteroaryl-(C 1 -C 3 )alkyloxy, aminocarbonyl, hydroxycarbonyl, (C 1 -C 4 alkyl)aminocarbonyl, di-(C 1 -C 3 alkyl)aminocarbonyl, (C 1 -C 4 alkyloxy)carbonyl, aminocarbonyl-(C 1 -C 3 )alkyl, (C 1 -C 4 alkyl)aminocarbonyl-(C 1 -C 3 )alkyl, di-(C 1 -C 3 alkyl)aminocarbonyl-(C 1 -C 3 )alkyl, hydroxycarbonyl-(C 1 -C 3 )alkyl, (C 1 -C 4 alkyloxy)carbonyl-(C 1 -C 3 )alkyl, (C 3 -C 7 )cycloalkyloxy-(C 1 -C 3 )alkyl, (C 5 -C 7 )cycloalkenyloxy-(C 1 -C 3 )alkyl, aryloxy-(C 1 -C 3 )alkyl, heteroaryloxy-(C 1 -C 3 )alkyl, alkylsulfonyloxy, arylsulfonyloxy, aryl-(C 1 -C 3 )alkyl-sulfonyloxy, trimethylsilyloxy, t-butyldimethylsilyloxy, and cyano;

wherein alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by substituents independently selected from chlorine, hydroxy, C 1 -C 3 alkoxy and C 1 -C 3 alkyl, and in cycloalkyl and cycloalkenyl groups or portions one or two methylene groups are optionally replaced independently of one another by NR b , O, S, CO, SO or SO 2 ;

when Y is hydrogen or C 1 -C 6 alkyl, then both R 8 and R 9 are hydroxy;

each R a is a member independently selected from the group consisting of H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and (C 1 -C 4 alkyl)carbonyl, wherein alkyl and cycloalkyl groups or portions are optionally partly or completely fluorinated;

each R b is a member independently selected from the group consisting of H, C 1 -C 4 alkyl and (C 1 -C 4 alkyl)carbonyl, wherein alkyl groups or portions are optionally partly or completely fluorinated;

each R c is a member independently selected from the group consisting of H, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, CHR d R e , SO 2 R d , C(O)OR d and C(O)NR d R e , wherein alkyl and cycloalkyl groups are optionally partly or completely fluorinated; and

R d and R e each independently represent H or C 1 -C 6 alkyl, wherein alkyl groups are optionally partly or completely fluorinated;

and pharmaceutically acceptable salts thereof.

2. A compound of claim 1 , wherein when V is a member selected from the group consisting of oxygen, sulfur and a single bond and W is C 1 -C 6 alkylene, then Y is other than hydrogen, C 1 -C 6 alkyl or (C 3 -C 10 cycloalkyl)C 1 -C 4 alkyl, wherein the cycloalkyl portion of Y is carbocyclic.

3. A compound of claim 1 , wherein V is selected from the group consisting of oxygen, sulfur and a single bond.

4. A compound of claim 3 , wherein V is selected from the group consisting of oxygen and a single bond.

5. A compound of claim 1 , wherein W is selected from the group consisting of C 1 -C 6 alkylene, C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, C 3 -C 10 cycloalkylene and (C 3 -C 10 cycloalkylene)(C 1 -C 6 alkylene).

6. A compound of claim 5 , wherein W is selected from the group consisting of C 1 -C 6 alkylene, C 2 -C 6 alkenylene and C 2 -C 6 alkynylene.

7. A compound of claim 1 , wherein X is selected from the group consisting of oxygen, sulfur, a single bond and NR a .

8. A compound of claim 7 , wherein X is selected from the group consisting of oxygen and a single bond.

9. A compound of claim 1 , wherein Y is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)C 1 -C 4 alkyl, (C 1 -C 4 alkyloxy)C 1 -C 3 alkyl, (C 3 -C 10 cycloalkyloxy)C 1 -C 3 alkyl, (amino)C 1 -C 3 alkyl, (C 1 -C 4 alkylamino)C 1 -C 3 alkyl, (C 1 -C 6 alkyl)carbonyl, (C 2 -C 6 alkenyl)carbonyl, (C 2 -C 6 alkynyl)carbonyl, (C 1 -C 6 alkyl)sulfonyl, (C 2 -C 6 alkenyl)sulfonyl, or (C 2 -C 6 alkynyl)sulfonyl, wherein alkyl, alkenyl, alkynyl and cycloalkyl groups or portions are optionally partly or completely fluorinated and are optonally mono- or disubstituted by substituents independently selected from chlorine, hydroxy, C 1 -C 3 alkyl, C 1 -C 3 alkoxy and C 3 -C 6 cycloalkyl, and in cycloalkyl groups or portions one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO 2 or NR b , and one or two methyne groups are optionally replaced by N.

10. A compound of claim 9 , wherein Y is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl and (C 1 -C 4 alkyloxy)C 1 -C 3 alkyl.

11. A compound of claim 1 , wherein Z is selected from the group consisting of oxygen, sulfur, or methylene optionally substituted with one to two substituents independently selected from halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl and C 3 -C 6 cycloalkyloxy.

12. A compound of claim 11 , wherein Z is methylene.

13. A compound of claim 1 , wherein R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkyloxy and cyano.

14. A compound of claim 13 , wherein R 1 , R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo and C 1 -C 6 alkyl.

15. A compound of claim 14 , wherein R 1 is selected from the group consisting of hydrogen, halo and C 1 -C 6 alkyl, and R 2 and R 3 are each hydrogen.

16. A compound of claim 1 , wherein R 4 and R 5 are each independently selected from the group consisting of hydrogen, halo, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkyloxy and cyano.

17. A compound of claim 16 , wherein R 4 and R 5 are each independently selected from the group consisting of hydrogen, halo and C 1 -C 6 alkyl.

18. A compound of claim 17 , wherein R 4 and R 5 are each hydrogen.

19. A compound of claim 1 , wherein R 6 , R 7 , R 8 and R 9 are each independently selected from the group consisting of hydroxy, halo, C 1 -C 6 alkyl, C 1 -C 6 alkyloxy, (C 3 -C 7 )cycloalkyloxy, aryloxy and (C 3 -C 7 )cycloalkyl-(C 1 -C 3 )alkyloxy, wherein alkyl and cycloalkyl groups or portions are optionally partly or completely fluorinated.

20. A compound of claim 19 , wherein R 6 , R 7 , R 8 and R 9 are each hydroxy.

21. A compound of claim 1 , having Formula IA:

wherein

R 1 is a member selected from the group consisting of hydrogen, halo and C 1 -C 6 alkyl;

V is a member selected from the group consisting of oxygen and a single bond;

W is a member selected from the group consisting of C 1 -C 6 alkylene, C 2 -C 6 alkenylene, C 2 -C 6 alkynylene, C 3 -C 10 cycloalkylene, and (C 3 -C 10 cycloalkylene)(C 1 -C 6 alkylene);

X is a member selected from the group consisting of oxygen, a single bond, and NR a ; and

Y is a member selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 cycloalkyl, (C 3 -C 10 cycloalkyl)C 1 -C 4 alkyl, (C 1 -C 4 alkyloxy)C 1 -C 3 alkyl, (C 3 -C 10 cycloalkyloxy)C 1 -C 3 alkyl, (amino)C 1 -C 3 alkyl, (C 1 -C 4 alkylamino)C 1 -C 3 alkyl, (C 1 -C 6 alkyl)carbonyl, (C 2 -C 6 alkenyl)carbonyl, (C 2 -C 6 alkynyl)carbonyl, (C 1 -C 6 alkyl)sulfonyl, (C 2 -C 6 alkenyl)sulfonyl, and (C 2 -C 6 alkynyl)sulfonyl,

wherein alkyl, alkenyl, alkynyl and cycloalkyl groups or portions of W, X and Y are optionally partly or completely fluorinated and optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, and C 3 -C 6 cycloalkyl, and in cycloalkyl groups or portions one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO 2 or NR b , and one or two methyne groups are optionally replaced by N.

22. A compound of claim 1 , selected from the group consisting of:

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(2-methoxyethoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(3-(4-(2-(allyloxy)ethoxy)benzyl)-4-chlorophenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(prop-2-ynyloxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(1-(prop-2-ynyloxy)propan-2-yloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(4-hydroxybut-2-ynyloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(4-methoxybut-2-ynyloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(cyclopentyloxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(443-cyclopropylprop-2-ynyloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(difluoromethoxy)ethyl)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(2,2,2-trifluoroethoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(cyclohex-2-enyloxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-((E)-3-cyclopropylallyloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(2-fluoroethoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(2,2-difluoroethoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(2-(pyrrolidin-1-yl)ethoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-((R)-tetrahydrofuran-3-yloxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-cyclobutoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(1-methylcyclopropoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethyl)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(cyclopropoxymethyl)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-cyclopropoxypropoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; and

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(3-cyclopropoxypropyl)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;

or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 .

24. A method of treating a disease or condition affected by inhibition of SGLT activity, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

25. A method of treating diabetes, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

26. A method in accordance with claim 25 , wherein said diabetes is type 1 diabetes.

27. A method in accordance with claim 25 , wherein said diabetes is type 2 diabetes.

28. A method in accordance with claim 25 , wherein said compound is administered in combination with a second therapeutic agent.

29. A method in accordance with claim 28 , wherein said second therapeutic agent is selected from the group consisting of antidiabetic agents, lipid-lowering/lipid-modulating agents, agents for treating diabetic complications, anti-obesity agents, antihypertensive agents, antihyperuricemic agents, and agents for treating chronic heart failure and atherosclerosis.

30. A method in accordance with claim 24 , wherein said disease or condition is selected from the group consisting of type 1 diabetes mellitus, type 2 diabetes mellitus, hyperglycemia, diabetic complications, insulin resistance, metabolic syndrome, hyperinsulinemia, hypertension, hyperuricemia, obesity, edema, dyslipidemia, chronic heart failure, and atherosclerosis.

31. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

Assignments (9)

Continuity (2)