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US 2024/0199602 A1Published application
Inhibitors of plasma kallikrein and uses thereof
AssigneeTakeda Pharmaceutical Company Limited
InventorsJeremy Travins, Thomas Miller, Nikolaos Papaioannou
Life of this patent
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Abstract
Provided herein are compounds that inhibit pKal, a serine protease whose activity is responsible for proteolytically cleaving kininogen and generating the potent vasodilator and pro-inflammatory peptide bradykinin, which can lead to painful and debilitating inflammatory attacks (e.g., edema). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating pKal-related diseases and disorders (e.g., edema) with the compounds in a subject, by administering the compounds and/or compositions described herein.
Claims34
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- A is substituted or unsubstituted heteroarylene, or substituted or unsubstituted heterocyclylene;
- R1 is —N(RA)2;
- R2 is substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —ORA, or —N(RA)2;
- R3 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted acyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroaralkyl, wherein any carbon of R3, valence permitting, is optionally replaced with —O—, —NRA—, —C(O)—, —C(═NRA)—, —S—, —S(O)—, or —S(O)2—;
- and
- each occurrence of RA is, independently, hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, or an oxygen protecting group when attached to an oxygen atom, or two RA groups are joined to form a substituted or unsubstituted heterocyclic ring.
4 more elements
Dependencies are inferred from the claim text.