Synthesis and biological evaluation of 1,3-dioxolane-based 5-HT1A receptor agonists for CNS disorders and neuropathic pain-Reference-Cited by-同舟云学术

Synthesis and biological evaluation of 1,3-dioxolane-based 5-HT1A receptor agonists for CNS disorders and neuropathic pain

Published:2018-09-01 Issue:18 Volume:10 Page:2137-2154
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Franchini Silvia¹,Bencheva Leda Ivanova¹,Battisti Umberto Maria¹,Tait Annalisa¹,Sorbi Claudia¹,Fossa Paola²,Cichero Elena²,Ronsisvalle Simone³,Aricò Giuseppina³,Denora Nunzio⁴,Iacobazzi Rosa Maria⁵,Cilia Antonio⁶,Pirona Lorenza⁶,Brasili Livio¹

Affiliation:

1. Dipartimento di Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, Via Campi 103, 41125 Modena, Italy

2. Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV 3, 16132 Genova, Italy

3. Dipartimento di Scienze del Farmaco Sezione di Chimica Farmaceutica e Sezione di Farmacologia e Tossicologia, Università degli Studi di Catania, Viale Andrea Doria 6, 95125, Catania, Italy

4. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, I-70125 Bari, Italy

5. Istituto tumori IRCCS “Giovanni Paolo II”, Via O. Flacco, 65, 70124 Bari, Italy

6. Divisione Ricerca e Sviluppo, Recordati S.p.A., Via Civitali 1, 20148 Milano, Italy

Abstract

Aim: Targeting 5-HT1A receptor (5-HT1AR) as a strategy for CNS disorders and pain control. Methodology: A series of 1,3-dioxolane-based 2-heteroaryl-phenoxyethylamines was synthesized by a convergent approach and evaluated at α1-adrenoceptors and 5-HT1AR by binding and functional experiments. Absorption, distribution, metabolism, excretion and toxicity prediction studies were performed to explore the drug-likeness of the compounds. Results & conclusion: The most promising compound, the pyridin-4-yl derivative, emerged as a potent and selective 5-HT1AR agonist (pKi = 9.2; pD2 = 8.83; 5-HT1A/α1 = 135). In vitro it was able to permeate by passive diffusion MDCKII-MDR1 monolayer mimicking the blood–brain barrier and showed promising neuroprotective activity.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

http://www.future-science.com/doi/pdf/10.4155/fmc-2018-0107

Reference40 articles.

1. The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor

2. 5-HT1A Receptor: An Old Target as a New Attractive Tool in Drug Discovery from Central Nervous System to Cancer

3. Serotonin and brain function: a tale of two receptors

4. The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder

5. NLX-112, a highly selective 5-HT 1A receptor agonist, mediates analgesia and antidepressant-like activity in rats via spinal cord and prefrontal cortex 5-HT 1A receptors, respectively

Cited by 10 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Advances in drug design and therapeutic potential of selective or multitarget 5‐HT1A receptor ligands;Medicinal Research Reviews;2024-05-29

2. Synthesis and biological activity of 5-acetyl- and 5-hydroxyalkyl1,3-dioxane derivatives;Fine Chemical Technologies;2023-10-08

3. SYNTHESIS, STRUCTURE AND BIOLOGICAL ACTIVITY OF 2,2,4-TRISUBSTITUTED OF 1,3-DIOXOLANES;ChemChemTech;2023

4. Meet the Editorial Board Member;Pharmaceutical Nanotechnology;2022-10

5. Effect of the replacement of the o-methoxyphenyl moiety with nitrogen-containing aromatic rings within N-phenyl-piperazine and phenoxy-ethylamine-based 1,3-dioxo/oxathio/dithiolanes as α1 and 5-HT1A receptor ligands;Results in Chemistry;2022-01