US 12,168,071 B2
Treprostinil derivatives and their use in pharmaceutical compositions
Hitesh Batra, Herndon, VA (US); Liang Guo, Vienna, VA (US); Patrick Poisson, Chapel Hill, NC (US); and Susovan Jana, Rockville, MD (US)
Assigned to United Therapeutics Corporation, Silver Spring, MD (US)
Filed by United Therapeutics Corporation, Silver Spring, MD (US)
Filed on Mar. 2, 2022, as Appl. No. 17/685,038.
Claims priority of provisional application 63/156,110, filed on Mar. 3, 2021.
Prior Publication US 2022/0280430 A1, Sep. 8, 2022
Int. Cl. C07D 471/04 (2006.01); A01N 43/90 (2006.01); A61K 9/00 (2006.01); A61K 9/14 (2006.01); A61K 31/5575 (2006.01); A61K 45/06 (2006.01)
CPC A61K 9/14 (2013.01) [A61K 9/0075 (2013.01); A61K 31/5575 (2013.01); A61K 45/06 (2013.01)] 21 Claims
 
1. A compound having the following formula:

OG Complex Work Unit Chemistry
wherein X is a salt moiety or a promoiety; wherein each of OR2 and OR3 has a lower reactivity with a carboxyl group than that of the respective hydroxyl group of unsubstituted treprostinil and C═OX has a lower reactivity with hydroxyl than that of the carboxyl group of unsubstituted treprostinil, wherein R2 and R3 are each independently selected from CH2OBn, CH2OH,

OG Complex Work Unit Chemistry
wherein Z is O or CH2; or wherein R2 and R3 are joined together to form an 8-12 membered heterocyclyl comprising
—C(O)—, —SO2—, or

OG Complex Work Unit Chemistry
and wherein
each R10 is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkenyl, optionally substituted cycloalkyl, optionally substituted heteroaryl, or optionally substituted aryl.