Prolyl hydroxylase inhibitors and methods of use
Inventors
Kawamoto, Richard Masaru • Wu, Shengde • Evdokimov, Artem G. • Greis, Kenneth D. • Boyer, Angelique Sun • Warshakoon, Namal C.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10729681-B2
Publication Date
2020-08-04
Expiration Date
Abstract
The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia.
Core Innovation
The disclosed invention provides HIF-1̲̲ prolyl hydroxylase inhibitors comprising a series of substituted aryl/heteroaryl amide and 3-hydroxy-pyridine-2-carbonyl amino-acid derivatives. The independent claim covers a compound having the depicted formula, or a pharmaceutically acceptable salt thereof, wherein R is selected from enumerated substituted phenyl groups. Tables and examples describe variations across aryl, heteroaryl, and side-chain substitutions.
The compounds stimulate HIF-1 target genes, stabilize HIF-1̲̲, and increase hypoxia-regulated factors including VEGF and erythropoietin, promoting tissue vascularization and erythropoietic responses. Disclosed characterization data demonstrate the inhibition of EGLN-1 and EGLN-3, induction of VEGF, and increased serum erythropoietin in animal data. The background section is omitted from the supplied material, so the specific problem being solved is not explicitly described in the patent.
Claims Coverage
The supplied relevant claims identify one independent claim directed to a compound having a depicted formula or a pharmaceutically acceptable salt thereof, alongside claims specifying a further depicted compound and therapeutic uses, presenting five inventive features across the claims.
Compound with specified substituted phenyl groups
The independent claim covers a compound having the depicted formula, or a pharmaceutically acceptable salt thereof, wherein R is selected from enumerated 2-, 3-, or 4-substituted phenyl groups including fluorophenyl, chlorophenyl, cyanophenyl, alkylphenyl (such as methylphenyl, ethylphenyl), alkoxyphenyl (such as methoxyphenyl, ethoxyphenyl, iso-propoxyphenyl), carbamoylphenyl, carbonyl-substituted phenyl (such as aziridine-1-carbonylphenyl, azetidine-1-carbonylphenyl, pyrrolidine-1-carbonylphenyl, piperidine-1-carbonylphenyl), and amino-substituted phenyl groups (such as acetylaminophenyl, ethanecarbonylaminophenyl, or cyclopropanecarbonylaminophenyl).
Further depicted compound
The claims specify a further depicted compound having the claimed formula, or a pharmaceutically acceptable salt thereof.
Treatment of anemia
The claims cover treating anemia by administering an effective amount of the compound or pharmaceutically acceptable salt to a human or mammal in need.
Promotion of wound healing
The claims cover promoting wound healing by administering an effective amount of the compound or pharmaceutically acceptable salt to a human or mammal in need.
Treatment of diseases affected by specified factors
The claims cover treating a disease affected by VEGF, GAPDH, or erythropoietin levels by administering an effective amount of the compound or pharmaceutically acceptable salt to a human or mammal in need.
The claims focus on the specified substituted-phenyl compound family and pharmaceutically acceptable salts thereof, encompassing a further depicted compound and therapeutic applications for anemia, wound healing, and diseases affected by specified factors.
Stated Advantages
The compounds are described as stimulating HIF-1 target genes and promoting tissue vascularization.
Inhibition of HIF-1̲̲ prolyl hydroxylase stabilizes HIF-1̲̲ and promotes angiogenic and erythropoietic responses.
Documented Applications
Treatment of anemia, including the claimed administration of an effective amount of the compound or pharmaceutically acceptable salt to a human or mammal in need.
Promotion of wound healing, including non-healing wounds, by administering an effective amount of the compound or pharmaceutically acceptable salt to a human or mammal in need.
Treatment of diseases affected by VEGF, GAPDH, or erythropoietin levels in a human or mammal in need.
Treatment of ischemia, peripheral vascular disease (PVD), coronary artery disease (CAD), and heart failure.
Interested in licensing this patent?