Treatment of obesity and pulmonary arterial hypertension

1. A method of treating a condition selected from the group consisting of obesity and pulmonary arterial hypertension comprising administering to a subject having obesity and/or pulmonary arterial hypertension a compound of formula (I) in an amount effective to treat obesity and/or pulmonary arterial hypertension,

wherein if the subject has obesity, the compound is administered in an amount effective to reduce glucose intolerance,

wherein if the subject has pulmonary arterial hypertension, the compound is administered in an amount effective to reduce right ventricular pulse pressure, and

wherein formula (I) is:

wherein

W is O or NR5;

R1 is H, —CH 3 , —(CH 2 ) 2 OH,

R2 is

R3 is —(CH 2 ) 5 CH 3 , —(CH 2 ) 6 CO 2 H, —(CH 2 ) 6 CO 2 CH 3 , —(CH 2 ) d NHCO-Ph, —(CH 2 ) 6 CONH-Ph, —(CH 2 ) 6 CONHCH 2 -Ph,

R4 and R5 are independently H or —CH 3 ;

R6 is O or NR9;

R7 is H, —CH 3 , —C(CH 3 ) 3 , —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 O(CH 2 ) 2 OH, —(CH 2 CH 2 O) 3 CH 3 , —(CH 2 CH 2 O) 2 CH 2 CO 2 CH 3 , —(CH 2 ) 5 CH 3 ,

R8 is H, —OH, —CH 2 OH, —CO 2 H, —CO 2 CH 2 CH 3 , —CO(CH 2 ) 6 CH 3 , —OCH 3 , —NH 2 , —SO 2 NH 2 , —CONH-Bn or

R9 is H or —CH 3 ;

R10 is —CH 2 NH 2 , —CO 2 H or —CO 2 CH 3 ;

R11 is —SO 2 -Ph, —CH 2 -Ph, —CONH-Ph, —COCH 3 ,

and

R12 is —CH 3

where X1, X2, X3, X4, X5, X6 and X7 are independently H, halogen, —OH, —CH 3 , —CF 3 , —OCH 3 , —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 H, —CH 2 CO 2 CH 3 , phenyl or —O-Bn; and

where a=0-2; b=1-6; c=0-1; d=4-7; and e=0-1;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein W is NR5.

3. The method of claim 1 , wherein R6 is NR9.

4. The method of claim 1 , wherein at least one of R4, R5 and R9 is H.

5. The method of claim 1 , wherein all of R4, R5 and R9 are H.

6. The method of claim 1 , wherein one of X1 and X2 is H, and the other is halogen, —CF 3 , —CH 3 , —CO 2 H, —CO 2 CH 3 , —OCH 3 or phenyl.

7. The method of claim 1 , wherein one of X3 and X4 is —OH, and the other is halogen, —CO 2 H or —CO 2 CH 3 .

8. The method of claim 1 , wherein X7 is H, —CF 3 or —OCH 3 .

9. The method of claim 1 , wherein X1 is located in meta position and X2 is located in para position.

10. The method of claim 1 , wherein X1 is located in ortho position and X2 is located in para position.

11. The method of claim 1 , wherein X3 is in meta position and X4 is in para position.

12. The method of claim 1 , wherein X5 or X6 is in meta position.

13. The method of claim 1 , wherein X5 or X6 is in para position.

14. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 , wherein

R1 is

R2 is

and

R3 is

and

where X1, X2, X3, X4, X5 and X6 are independently H, halogen, —OH, —CH 3 , —CF 3 , —OCH 3 , —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 H or —CH 2 CO 2 CH 3 , and

where a=1-2; and b=1-5;

or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein

R1 is

R2 is

and

R3 is

and

where X1 is H or halogen;

where X4 is H, halogen or —CO 2 H; and

where X5 is H, halogen or —OCH 3 ;

or a pharmaceutically acceptable salt thereof.

19. The method of claim 1 , where R5 is H.

20. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 , wherein the halogen is Br, Cl or F.

22. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

23. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

24. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.