Methods for treating obesity employing an SGLT2 inhibitor
View Patent ↗Methods are provided for treating obesity or causing weight loss in a mammalian subject or patient, wherein a therapeutically effective amount of an SGLT2 inhibitor alone or optionally in combination with another anti-obesity agent, is administered to a mammalian subject or patient. In addition, a pharmaceutical composition is provided which comprises an SGLT2 inhibitor, alone or in combination with another anti-obesity agent, and a pharmaceutically acceptable carrier thereof.
1. A method for treating obesity in a mammalian subject or patient comprising administering to a mammalian subject or patient in need of such treatment a therapeutically effective amount of an SGLT2 inhibitor, wherein said amount is below the effective amount for treating diabetes and said SGLT2 inhibitor has the structure
wherein
R 1 , R 2 and R 2a are independently hydrogen, OH, OR 5 , alkyl, CF 3 , OCHF 2 , OCF 3 , SR 5i or halogen, or two of R 1 , R 2 and R 2a together with the carbons to which they are attached can form an annelated five, six or seven membered carbocycle or heterocycle which can contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO 2 ;
R 3 and R 4 are independently hydrogen, OH, OR 5a , OAryl, OCH 2 Aryl, cycloalkyl, CF 3 , —OCHF 2 —OCF 3 , halogen, —CN, —CO 2 R 5b , —CO 2 H, COR 6b , —CH(OH)R 6c , —CH(OR 5h )R 6d , —CONR 6 R 6a , —NHCOR 5c , —NHSO 2 R 5d , —NHSO 2 Aryl, Aryl, —SR 5e , —SOR 5f , —SO 2 R 5g , —SO 2 Aryl, or a five, six or seven membered heterocycle which can contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO 2 , or R 3 and R 4 together with the carbons to which they are attached form an annelated five, six or seven membered carbocycle or heterocycle which can contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO 2 ;
R 5 , R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g , R 5h and R 5i are independently alkyl;
R 6 , R 6a , R 6b , R 6c , and R 6d are independently hydrogen, alkyl, aryl, alkylaryl or cycloalkyl, or R 6 and R 6a together with the nitrogen to which they are attached form an annelated five, six or seven membered heterocycle which can contain 1 to 4 heteroatoms in the ring which are N, O, S, SO, and/or SO 2 ;
A is O, S, NH, or (CH 2 ) n where n is 0-3, or a pharmaceutically acceptable salt, stereoisomer, or prodrug ester thereof;
with the proviso that where A is (CH 2 ) n where n is 0, 1, 2, or 3 or A is O, and at least one of R 1 , R 2 , and R 2a is OH or OR 5 , then at least one of R 1 , R 2 , and R 2a is CF 3 , OCF 3 , or OCHF 2 and/or at least one of R 3 and R 4 is CF 3 , —OCHF 2 , —OCF 3 , —CN, —CO 2 R 5b , CH(OR 5h )R 6d , CH(OH)R 6c , COR 6b , —NHCOR 5c , —NHSO 2 R 5d , —NHSO 2 Aryl, Aryl, —SR 5e , —SOR 5f , —SO 2 R 5g or —SO 2 Aryl.
2. The method according to claim 1 , wherein the mammal is a human.
3. The method according to claim 1 , wherein the mammal is a human with type II diabetes mellitus.
4. The method according to claim 1 , wherein the SGLT2 inhibitor is selected from the group consisting of dapagliflozin and dapagliflozin-PGS.
5. The method according to claim 1 , wherein the SGLT2 inhibitor has the structure
wherein
A is CH 2 ; R 1 is hydrogen, halogen or lower alkyl; R 2 and R 2a are each H; R 3 is H; R 4 is COR 6b , —CH(OH)R 6c , —CH(OR 5h )R 6d , R 5a O, —OCHF 2 , —OCF 3 or —SR 5e .
6. The method according to claim 1 , wherein the SGLT2 inhibitor has the structure
7. The method according to claim 4 , wherein the SGLT2 inhibitor is dapagliflozin.
8. The method according to claim 7 , wherein dapagliflozin is provided as a propylene glycol hydrate.