Stereoselective Synthesis and Antiallodynic Activity of 3‐Hydroxylated Paroxetines

• Published in: ChemMedChem Vol. 16; no. 3; pp. 472 - 476
• Main Authors: Chamorro‐Arenas, Delfino, Salgado‐Moreno, Giovanna, Martinez‐Mendieta, Liliana, Quintero, Leticia, Godínez‐Chaparro, Beatriz, Sartillo‐Piscil, Fernando
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 04-02-2021
• Subjects: alkaloids; allodynia; Analgesics; neuropathic pain; Paroxetine; stereoselective synthesis; Stereoselectivity; Synthesis; allodynia; neuropathic pain; paroxetine; alkaloids; stereoselective synthesis
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202000674

The design, stereoselective synthesis and in vivo antiallodynic activity of four novel paroxetine analogs, named 3‐hydroxy paroxetines (3HPXs), is reported herein. Among the novel synthesized compounds, three showed an antiallodynic effect, while (R,R)‐3HPX was found to be 2.5 times more bioactive than (‐)‐paroxetine itself in neuropathic rats. Consequently, the current investigation not only discloses a novel promising analgesic drug, but also reveals that functionalization at the C3 position of paroxetine could be as effective as the common functionalization at either C4 or within the sesamol group.
Neuropathic pain relief: Herein we disclose a synthetic alkaloid (R,R‐3HPX, highlighted in blue) as a promising analgesic drug. Among the compounds synthesized in this work, three showed an antiallodynic effect, while (R,R)‐3HPX was found to be 2.5 times more bioactive than (‐)‐paroxetine itself in neuropathic rats. Out study shows that functionalization at the C3 position of paroxetine could be as effective as the common functionalization at either C4 or within the sesamol group.