Treprostinil derivatives and compositions and uses thereof

1. A compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates, hydrates, clathrates, polymorphs and stereoisomers thereof.

2. A method of treating a medical condition responsive to treatment with treprostinil, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula (II):

wherein:

—O—Z—CO 2 H is

 —O-heteroalkyl-CO 2 H, —O-cyclyl-CO 2 H, —O—CH 2 -cyclyl-CO 2 H, —O-cyclyl-CH 2 —CO 2 H, or —O—CH 2 -cyclyl-CH 2 —CO 2 H, each of which may optionally be substituted,

wherein:

-cyclyl- is -cycloalkyl-, -heterocyclyl-, -aryl- or -heteroaryl-;

R 7 and R 8 in each occurrence independently are hydrogen, C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl, or R 7 and R 8 and the carbon atom to which they are connected form a C 3 -C 6 cycloalkyl ring; and

n is an integer from 1 to 10;

with the proviso that —O—Z—CO 2 H is not

 and does not contain a sugar moiety;

or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.

3. The method of claim 2 , wherein —O—Z—CO 2 H is

and wherein

R 7 and R 8 are as defined as in claim 2 ;

p is an integer from 1 to 9; and

q is an integer from 0 to 8.

4. The method of claim 3 , wherein both R 7 and R 8 are hydrogen, and p is an integer from 1 to 9 or from 1 to 5 (or each occurrence of R 7 and R 8 is hydrogen, and q is an integer from 0 to 8 or from 0 to 4).

5. The method of claim 3 , wherein —O—Z—CO 2 H is

and p is an integer from 2 to 9 or from 2 to 5.

6. The method of claim 2 , wherein —O—Z—CO 2 H is —O-heteroalkyl-CO 2 H, and —O-heteroalkyl-CO 2 H is selected from the group consisting of:

wherein r is each of 1,2 and 3.

7. The method of claim 2 , wherein —O—Z—CO 2 H is —O-cycloalkyl-CO 2 H, —O—CH 2 -cycloalkyl-CO 2 H, —O-cycloalkyl-CH 2 —CO 2 H, or —O—CH 2 -cycloalkyl-CH 2 —CO 2 H, and for each of the preceding moieties -cycloalkyl- is:

1,2-cyclopropyl (cis or trans); or

1,3-cyclobutyl (cis or trans) or 1,2-cyclobutyl (cis or trans); or

1,3-cyclopentyl (cis or trans) or 1,2-cyclopentyl (cis or trans); or

1,4-cyclohexyl (cis or trans), 1,3-cyclohexyl (cis or trans), or 1,2-cyclohexyl (cis or trans).

8. The method of claim 2 , wherein the compound is selected from the group consisting of:

and pharmaceutically acceptable salts, solvates, hydrates, clathrates, polymorphs and stereoisomers thereof.

9. The method of claim 2 , wherein the medical condition is selected from the group consisting of pulmonary hypertension, pulmonary fibrosis, peripheral ischemic lesions on the skin, critical limb ischemia, diabetic neuropathic foot ulcer, kidney malfunction and failure, peripheral vascular disease, atherogenesis, congestive heart failure, tumors, cancers, and pain associated with each of the preceding conditions.

10. The method of claim 9 , wherein the medical condition is pulmonary hypertension.

11. The method of claim 10 , wherein the medical condition is pulmonary arterial hypertension.

12. The method of claim 11 , further comprising administering a vasoactive agent, a diuretic, an anticoagulant or a cardiac glycoside, or any combination thereof.

13. The method of claim 2 , wherein the compound is administered transdermally.

14. The method of claim 13 , wherein the compound is administered via a transdermal patch.