Treprostinil derivatives and compositions and uses thereof
AssigneeCorsair Pharma, Inc.
InventorsXiaoming ZHANG, Meenakshi S. VENKATRAMAN, Cyrus K. BECKER
Life of this patent
Estimating the term…
Abstract
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.
Claims28
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;
- 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)NR9 R10;
- 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 benzoate;
- neither —OR1 nor —OR2 forms a substituted cyclohexane-ester;
- neither —OR1 nor —OR2 forms an ester with or of an amino acid (protected or unprotected), a peptide or a protein;
- and
- the compound of Formula (I) is not a homopolymer or heteropolymer of treprostinil, or does not contain more than one molecule or unit of treprostinil.
A compound of Formula (II):
- wherein:
- —O—Z—CO2H is
- —O-heteroalkyl-CO2H, —O-cyclyl-CO2H, —O-CH2-cyclyl-CO2H, —O-cyclyl-CH2—CO2H, or —O-CH2-cyclyl-CH2—CO2H, each of which may optionally be substituted,
- wherein:
- -cyclyl- is -cycloalkyl-, -heterocyclyl-, -aryl- or -heteroaryl-;
- R7 and R8 in each occurrence independently are hydrogen, C1-C6 alkyl or C3-C6 cycloalkyl, or R7 and R8 and the carbon atom to which they are connected form a C3-C6 cycloalkyl ring;
- and
- n is an integer from 1 to 10;
- or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof, with the proviso that:
- —O—Z—CO2H is not
- and
- —O—Z—CO2H does not contain a sugar moiety.
A pharmaceutical composition comprising a compound of Formula (I) or Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof, and one or more pharmaceutically acceptable excipients or carriers.
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 (I) or Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, clathrate, polymorph or stereoisomer thereof.
Dependencies are inferred from the claim text.