Treprostinil derivative compounds and methods of using same

A transdermal patch comprising a topical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt, polymorph or stereoisomer thereof:

• wherein:
• R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35 and R36 are independently H or deuterium;
• Z is P1, wherein P1 is selected from:
• wherein:
• m is 1, 2, 3 or 4;
• R14 and R15 are independently in each occurrence selected from H, alkyl, cycloalkyl, alkylcycloalkyl, haloalkyl, heteroalkyl, substituted alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, substituted aryl, substituted heteroaryl, substituted arylalkyl, and substituted heteroarylalkyl;
• or
• R14 and R15 together with the atoms to which they are attached optionally form a 5- to 7-membered ring incorporating two ring heteroatoms chosen from N, O and S, which is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halo, methyl and methoxy;
• R18 and R19 are independently in each occurrence hydrogen or alkyl, wherein the alkyl is unsubstituted or substituted with 1 substituent selected from halo, hydroxy, alkoxy, amino, thio, methylthio, —C(O)OH, —C(O)O-(alkyl), —CONH2, aryl and heteroaryl, wherein the aryl or heteroaryl is unsubstituted or substituted with a substituent selected from alkyl, halo, haloalkyl, hydroxy, alkoxy, and haloalkoxy;
• R14 and R18 together with the atoms to which they are attached optionally form a 5- to 7-membered ring;
• R14 and R19 together with the atoms to which they are attached optionally form a 5- to 7-membered ring;
• R15 and R18 together with the atoms to which they are attached optionally form a 5- to 7-membered ring;
• and
• R15 and R19 together with the atoms to which they are attached optionally form a 5- to 7-membered ring;
• and
• R1 and R2 are independently H or P2, wherein P2 is selected from:
• wherein:
• m is 1, 2, 3 or 4;
• and
• R14 is independently in each occurrence selected from H, alkyl, cycloalkyl, alkylcycloalkyl, haloalkyl, heteroalkyl, substituted alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, substituted aryl, substituted heteroaryl, substituted arylalkyl, and substituted heteroarylalkyl.