It is now well established that sigma receptors are an independent class of receptors expressed in peripheral organs and in the central nervous system. There are at least two identified subtypes, namely sigma1 and sigma2, with distinct functional roles and different pharmacological characteristics. On the basis of their neuroregulative and neuropotective functions sigma1 agents could be potentially used for the treatment of depression and psychiatric disorders. The finding of high concentration of sigma2 receptors in neuronal and non-neuronal tumor cell lines provides evidence of a possible role in anticancer therapy. A variety of chemically unrelated compounds is able to bind sigma receptors, however only few bind with high affinity and selectivity to sigma receptor subtypes. This situation has given new impulse to medicinal chemists for the search of new and more selective ligands.We have recently reported that substituted 1-benzylpiperazine and 4-benzylpiperidine derivatives were shown to be high-affinity sigma ligands (Ki in the nanomolar range) with a slight preference for sigma1 over sigma2 receptors1-2. With the aim to improve sigma1/sigma2 selectivity we have studied the effect of some substitutions of the oxygen atoms on the 1,3-dioxolane ring by synthesizing 1,3-oxathiolane, 1,3-dithiolane, tetrahydro-furan, cyclopentanone and cyclopentanol derivatives as depicted below. A spiro derivative was additionally prepared and tested to study the influence of the two aromatic rings on receptor affinity. The preliminary pharmacological results show a significant improvement of sigma1 selectivity for compound A. Structure-activity relationship will be extensively discussed during the congress.

Synthesis and pharmacological evaluation of 1-benzylpiperazine and 4-benzylpiperidine as potent sigma ligands / Baraldi, Anna Maria; Franchini, Silvia; Prandi, Adolfo; O., Prezzavento; G., Ronsisvalle; L., Pirona; Brasili, Livio. - STAMPA. - ...:(2007), pp. 71-71. ((Intervento presentato al convegno XVIII Convegno Nazionale della Divisione di Chimica farmceutica della Società Chimica Italiana tenutosi a Chieti-Pescara nel 16-20 Settembre 2007.

Synthesis and pharmacological evaluation of 1-benzylpiperazine and 4-benzylpiperidine as potent sigma ligands.

BARALDI, Anna Maria;FRANCHINI, Silvia;PRANDI, adolfo;BRASILI, Livio
2007

Abstract

It is now well established that sigma receptors are an independent class of receptors expressed in peripheral organs and in the central nervous system. There are at least two identified subtypes, namely sigma1 and sigma2, with distinct functional roles and different pharmacological characteristics. On the basis of their neuroregulative and neuropotective functions sigma1 agents could be potentially used for the treatment of depression and psychiatric disorders. The finding of high concentration of sigma2 receptors in neuronal and non-neuronal tumor cell lines provides evidence of a possible role in anticancer therapy. A variety of chemically unrelated compounds is able to bind sigma receptors, however only few bind with high affinity and selectivity to sigma receptor subtypes. This situation has given new impulse to medicinal chemists for the search of new and more selective ligands.We have recently reported that substituted 1-benzylpiperazine and 4-benzylpiperidine derivatives were shown to be high-affinity sigma ligands (Ki in the nanomolar range) with a slight preference for sigma1 over sigma2 receptors1-2. With the aim to improve sigma1/sigma2 selectivity we have studied the effect of some substitutions of the oxygen atoms on the 1,3-dioxolane ring by synthesizing 1,3-oxathiolane, 1,3-dithiolane, tetrahydro-furan, cyclopentanone and cyclopentanol derivatives as depicted below. A spiro derivative was additionally prepared and tested to study the influence of the two aromatic rings on receptor affinity. The preliminary pharmacological results show a significant improvement of sigma1 selectivity for compound A. Structure-activity relationship will be extensively discussed during the congress.
XVIII Convegno Nazionale della Divisione di Chimica farmceutica della Società Chimica Italiana
Chieti-Pescara
16-20 Settembre 2007
Baraldi, Anna Maria; Franchini, Silvia; Prandi, Adolfo; O., Prezzavento; G., Ronsisvalle; L., Pirona; Brasili, Livio
Synthesis and pharmacological evaluation of 1-benzylpiperazine and 4-benzylpiperidine as potent sigma ligands / Baraldi, Anna Maria; Franchini, Silvia; Prandi, Adolfo; O., Prezzavento; G., Ronsisvalle; L., Pirona; Brasili, Livio. - STAMPA. - ...:(2007), pp. 71-71. ((Intervento presentato al convegno XVIII Convegno Nazionale della Divisione di Chimica farmceutica della Società Chimica Italiana tenutosi a Chieti-Pescara nel 16-20 Settembre 2007.
File in questo prodotto:
File Dimensione Formato  
POSTERCHIETI.ppt

non disponibili

Tipologia: Altro materiale allegato
Dimensione 704.5 kB
Formato Microsoft Powerpoint
704.5 kB Microsoft Powerpoint   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/715648
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact