Treprostinil derivatives and compositions and uses thereof
The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.
1. A compound of the following formula:
wherein ring A is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and u is an integer from 0 to 9;
or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.
2. The compound of claim 1 , wherein ring A is cyclopropyl and u is an integer from 0 to 9 or from 0 to 5.
3. The compound of claim 2 , which is
or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.
4. A pharmaceutical composition comprising a compound of the following formula:
wherein ring A is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and u is an integer from 0 to 9;
or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof, and one or more pharmaceutically acceptable excipients or carriers.
5. The pharmaceutical composition of claim 4 , wherein ring A is cyclopropyl and u is an integer from 0 to 9 or from 0 to 5.
6. The pharmaceutical composition of claim 5 , wherein the compound is
or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.
7. The pharmaceutical composition of claim 4 , which is formulated for transdermal delivery of the compound.
8. The pharmaceutical composition of claim 7 , which is formulated as a transdermal patch.
9. 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 the following formula:
wherein ring A is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, and u is an integer from 0 to 9;
or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.
10. The method of claim 9 , wherein the medical condition is selected from the group consisting of pulmonary hypertension, pulmonary fibrosis, interstitial lung disease, asthma, congestive heart failure, peripheral vascular disease, severe intermittent claudication, atherogenesis, ischemic lesions, critical limb ischemia, neuropathic foot ulcers, kidney malfunction and failure, immunosuppression, proliferative disorders, and pain associated with each of the preceding conditions.
11. The method of claim 10 , wherein the medical condition is pulmonary hypertension.
12. The method of claim 11 , wherein the medical condition is pulmonary arterial hypertension.
13. The method of claim 9 , wherein ring A is cyclopropyl and u is an integer from 0 to 9 or from 0 to 5.
14. The method of claim 13 , wherein the compound is
or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.
15. The method of claim 9 , wherein the compound is administered transdermally.
16. The method of claim 15 , wherein the compound is administered via a transdermal patch.
17. The method of claim 9 , further comprising administering an additional therapeutic agent.
18. The method of claim 17 , wherein the additional therapeutic agent comprises a vasoactive agent, a diuretic, an anticoagulant or a cardiac glycoside, or any combination thereof.