Treprostinil derivative compounds and methods of using same

Inventors

BECKER, Cyrus K. • Venkatraman, Meenakshi S. • Zhang, Xiaoming • Pfister, Jürg R. • Rescourio, Gwenaella

Assignees

Corsair Pharma Inc

Abstract

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Core Innovation

The invention provides transdermal patch topical compositions that comprise a compound of Formula (I) or a pharmaceutically acceptable salt, polymorph or stereoisomer thereof. The compounds include deuterium variants in which R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35 and R36 are independently H or deuterium. The variable group Z is P1, and R1 and R2 are independently H or P2, with P1 and P2 selected from defined structural options parameterized by m being 1, 2, 3 or 4.

The structural definitions further include broad substituent options for R14 and R15, and optional ring-forming combinations in which R14 and R15 together form a 5- to 7-membered ring incorporating two ring heteroatoms chosen from N, O and S, optionally substituted with halo, methyl and methoxy. Additional optional ring formations are defined for R14 with R18, R14 with R19, R15 with R18, and R15 with R19. R18 and R19 are independently hydrogen or alkyl with defined substitution options, and the substituent vocabularies for alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, haloalkyl, and substituted variants are explicitly enumerated.

The disclosure also describes treprostinil and prostacyclin-analog prodrug derivative compounds, including deuterated isotopologues and structures described in terms of enantiomers, salts, solvates, and polymorphs. The technical goal is improving systemic bioavailability and enabling oral or especially transdermal delivery. The compounds are described for treatment of pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH).

Claims Coverage

The consolidated claim coverage includes one independent claim directed to a transdermal patch topical composition with a Formula (I) compound or a pharmaceutically acceptable salt, polymorph or stereoisomer thereof. The independent claim content centers on five inventive features: H/deuterium substitution at R20-R36, Z defined as P1, R1/R2 defined as H or P2, and detailed R14/R15 and R18/R19 substituent and ring-forming constraints.

Overall, the independent claim coverage is directed to a transdermal patch topical composition containing Formula (I) compounds with tightly defined hydrogen/deuterium placement, P1 and P2 structural selection, and multiple optional ring-forming and substituent constraints.

Stated Advantages

Documented Applications