The hallmark of joint diseases, such as osteoarthritis (OA), is pain, originating from both inflammatory and neuropathic components, and compounds able to modulate the signal trans- duction pathways of the cannabinoid type-2 receptor (CB2R) can represent a helpful option in the treatment of OA. In this perspective, a set of 18 cannabinoid type-2 receptor (CB2R) ligands was developed based on an unprecedented structure. With the aim of improving the physicochemical properties of previously reported 4-hydroxy-2-quinolone-3-carboxamides, a structural opti- mization program led to the discovery of isosteric 7-hydroxy-5- oxopyrazolo[4,3-b]pyridine-6-carboxamide derivatives. These new compounds are endowed with high affinity for the CB2R and moderate to good selectivity over the cannabinoid type-1 receptor (CB1R), associated with good physicochemical characteristics. As to the functional activity at the CB2R, compounds able to act either as agonists or as inverse agonists/antagonists were discovered. Among them, compound 51 emerged as a potent CB2R agonist able to reduce pain in rats carrying OA induced by injection of monoiodoacetic acid (MIA).

Mugnaini, C., Kostrzewa, M., Bryk, M., Mokhtar Mahmoud, A., Brizzi, A., Lamponi, S., et al. (2020). Design, Synthesis, and Physicochemical and Pharmacological Profiling of 7‐Hydroxy-5-oxopyrazolo[4,3‐b]pyridine-6-carboxamide Derivatives with Antiosteoarthritic Activity In Vivo. JOURNAL OF MEDICINAL CHEMISTRY, 63(13), 7369-7391 [10.1021/acs.jmedchem.0c00595].

Design, Synthesis, and Physicochemical and Pharmacological Profiling of 7‐Hydroxy-5-oxopyrazolo[4,3‐b]pyridine-6-carboxamide Derivatives with Antiosteoarthritic Activity In Vivo

Claudia Mugnaini
;
Antonella Brizzi;Stefania Lamponi;Gianluca Giorgi;Federico Corelli
2020-01-01

Abstract

The hallmark of joint diseases, such as osteoarthritis (OA), is pain, originating from both inflammatory and neuropathic components, and compounds able to modulate the signal trans- duction pathways of the cannabinoid type-2 receptor (CB2R) can represent a helpful option in the treatment of OA. In this perspective, a set of 18 cannabinoid type-2 receptor (CB2R) ligands was developed based on an unprecedented structure. With the aim of improving the physicochemical properties of previously reported 4-hydroxy-2-quinolone-3-carboxamides, a structural opti- mization program led to the discovery of isosteric 7-hydroxy-5- oxopyrazolo[4,3-b]pyridine-6-carboxamide derivatives. These new compounds are endowed with high affinity for the CB2R and moderate to good selectivity over the cannabinoid type-1 receptor (CB1R), associated with good physicochemical characteristics. As to the functional activity at the CB2R, compounds able to act either as agonists or as inverse agonists/antagonists were discovered. Among them, compound 51 emerged as a potent CB2R agonist able to reduce pain in rats carrying OA induced by injection of monoiodoacetic acid (MIA).
2020
Mugnaini, C., Kostrzewa, M., Bryk, M., Mokhtar Mahmoud, A., Brizzi, A., Lamponi, S., et al. (2020). Design, Synthesis, and Physicochemical and Pharmacological Profiling of 7‐Hydroxy-5-oxopyrazolo[4,3‐b]pyridine-6-carboxamide Derivatives with Antiosteoarthritic Activity In Vivo. JOURNAL OF MEDICINAL CHEMISTRY, 63(13), 7369-7391 [10.1021/acs.jmedchem.0c00595].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1138727
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo