Selective alpha-2c adrenergic receptor agonists and uses thereof
AssigneeAlpheraBio LLC
InventorsLingyu ZHU, Zhiqiang CHENG
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Abstract
The present disclosure relates to selective alpha-2C adrenergic receptor agonists and uses thereof. In particular, the present disclosure relates to compounds of formula (I). These compounds can be useful as alpha-2C adrenergic receptor agonists for the treatment or prevention of disease thereof. In addition, the present disclosure describes the first discovered therapeutic use of these compounds against Tumor Necrosis Factor-α (TNF-α)-mediated inflammatory and autoimmune diseases, since these compounds can significantly inhibit lipopolysaccharide (LPS)-induced inflammatory responses and effectively down-regulate the expression, production and secretion of TNF-α.
Claims27
A compound of formula (I):
- or a stereoisomer, tautomer, pharmaceutically acceptable salt or a solvate thereof,
- wherein,
- ring A is a bicyclic ring;
- R1 is chosen from —C0-12 haloalkyl, —C(O)—C0-12 alkyl, —C(O)—C0-12 haloalkyl, —C(O)-aryl, —C(O)-heteroaryl, C0-12 alkylene-COOH, —C(O)—NR3R3′, —CN, —NR3R3′, —N3C(O) R3′, —NR3—SO2—R3′, —O—C0-12 alkyl, —SO2—R3, —SO2—NR3R3′, —C0-12 alkylene-C2-12 heteroaryl, and —C0-12 alkylene-C2-12 heterocyclyl;
- R2 is chosen from hydrogen, halogen, haloalkyl, and alkyl;
- and
- each of R3 and R3′ is independently hydrogen, haloalkyl, or alkyl.
A compound selected from the group consisting of:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt or a solvate thereof.
A method of treating or preventing a disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a selective alpha-2C adrenergic receptor (ADRA2C) agonist.
A method of selectively activating alpha-2C adrenergic receptor in a subject in need thereof, the method comprising administering to the subject an effective amount of a selective alpha-2C adrenergic receptor (ADRA2C) agonist.
A method of down-regulating TNF-α in a subject in need thereof, the method comprising administering to the subject an effective amount of a selective alpha-2C adrenergic receptor (ADRA2C) agonist.
Dependencies are inferred from the claim text.