Treprostinil derivatives and compositions and uses thereof

A method of promoting vasodilation, inhibiting platelet activation or aggregation, inhibiting thrombus formation, stimulating thrombolysis, inhibiting atherogenesis, inhibiting cell proliferation, promoting endothelial cell membrane remodeling, reducing inflammation, or providing cytoprotection, comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of Formula (I):

• wherein R1 and R2 independently are hydrogen,
• wherein:
• R3 in each occurrence independently is alkyl, -alkylaryl, cycloalkyl, heterocyclyl, aryl or heteroaryl, each of which may optionally be substituted with one to six substituents independently selected from the group consisting of halide, cyano, nitro, hydroxyl, —SH, —NH2, —OR11, —SR11, —NR12R13, —C(═O)R11, —C(═O)OR11, —OC(═O)R11, —C(═O)NR12R13, —NR11C(═O)R11, cycloalkyl, heterocyclyl, aryl, heteroaryl and unsubstituted alkyl, wherein:
• R11 in each occurrence independently is hydrogen, cycloalkyl, heterocyclyl, aryl, heteroaryl or unsubstituted alkyl;
• and
• R12 and R13 in each occurrence independently are hydrogen, cycloalkyl, heterocyclyl, aryl, heteroaryl or unsubstituted alkyl, or R12 and R13 and the nitrogen atom to which they are connected form a heterocyclic or heteroaryl ring;
• R4 and R5 in each occurrence independently are hydrogen, C1-C6 alkyl or C3-C6 cycloalkyl, or R4 and R5 and the carbon atom to which they are connected form a C3-C6 cycloalkyl ring;
• R6 in each occurrence independently is hydrogen, R3, —C(═O)R3, —C(═O)OR3 or —C(═O)NR9R10;
• or
• R6 and R4 or R5, together with the atoms to which they are connected, form a heterocyclic ring;
• R9 and R10 in each occurrence independently are hydrogen, alkyl, -alkylaryl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
• or
• R9 and R10 and the nitrogen atom to which they are connected form a heterocyclic or heteroaryl ring;
• j in each occurrence independently is an integer from 0 to 4;
• and
• m in each occurrence independently is an integer from 1 to 10;
• or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof, with the proviso that:
• both R1 and R2 are not hydrogen;
• neither —OR1 nor —OR2 forms an acetate;
• neither —OR1 nor —OR2 forms a substituted cyclohexane-ester;
• and
• neither —OR1 nor —OR2 forms an ester with or of an amino acid (protected or unprotected), a peptide or a protein.