US 12,337,001 B2
Neutral endopeptidase (NEP) and human soluble endopeptidase (hSEP) inhibitors to reduce detrimental effects of perfusion deficiency of parenchymal organs
Christopher Turski, Waunakee, WI (US)
Appl. No. 16/964,984
Filed by Christopher Turski, Waunakee, WI (US)
PCT Filed Jan. 31, 2019, PCT No. PCT/PL2019/000013
§ 371(c)(1), (2) Date Jul. 26, 2020,
PCT Pub. No. WO2019/151883, PCT Pub. Date Aug. 8, 2019.
Claims priority of application No. 424453 (PL), filed on Jan. 31, 2018.
Prior Publication US 2021/0047352 A1, Feb. 18, 2021
Int. Cl. A61K 31/55 (2006.01); A61K 31/675 (2006.01); A61P 25/00 (2006.01); C07D 225/06 (2006.01); C07F 3/04 (2006.01); C07F 9/553 (2006.01)
CPC A61K 31/55 (2013.01) [A61K 31/675 (2013.01); A61P 25/00 (2018.01); C07D 225/06 (2013.01); C07F 3/04 (2013.01); C07F 9/5535 (2013.01)] 20 Claims
 
1. A method of treating perfusion deficiency of an organ or part thereof in a human subject as measured by an elevated concentration of a biomarker in one or more bodily fluids wherein the organ is the brain or part thereof, comprising administering a therapeutically effective amount of a compound of the general formula (4):

OG Complex Work Unit Chemistry
wherein A is CH2,
wherein R2 and R3 independently represent hydrogen;
R4 and R6 independently represent hydrogen or a group that forms a biolabile carboxylic ester; and R5 is selected from the group consisting of -alkyl-(C1-C6)-phenyl, and -alkyl-(C1-C6)-naphthyl,
or a pharmaceutically acceptable salt or stereoisomer thereof; wherein the biomarker is selected from the group consisting of Endothelin-1 biomarker, pre-Endothelin-1, Pro-Endothelin (Big Endothelin-1), endothelin-1 converting enzyme (ECE-1), neutral endopeptidase (NEP), human soluble endopeptidase (hSEP), and combinations thereof.