A serie of dihydrothienocyclopentapyrazole-based derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The major term, the 6-methyl-1-(1,4-dichlorophenyl)-N-piperidinyl)- 1,4-dihydrothieno[20 ,30 -4,5]cyclopenta[1,2-c]pyrazole-3-carboxamide (6a), displayed a high affinity and good selectivity for CB2 receptors (Ki values of 2.30 nM for CB2 receptor and 440 nM for CB1 receptors respectively). Subsequent analogue preparation resulted in the identification of compounds such as 6b, 6d, 6e, 6k, 6l, 6m, 6s and 6t that showed 1.3e485 fold selectivity for CB2 receptors with potencies in the 1.1e7.2 nM range. These compounds profiled as full agonists at CB2 receptor in an inhibition assay of P- ERK 1/2 up regulation in HL-60 cells.

Tricyclic pyrazoles Part 7. Discovery of potent and selective dihydrothienocyclopentapyrazole derived CB2 ligands / Pinna, G; Curzu, Maria Michela; Dore, A; Lazzari, P; Ruiu, S; Pau, Amedeo; Murineddu, Gabriele; Pinna, Gerard Aime. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 85:(2014), pp. 747-757. [10.1016/j.ejmech.2014.08.042]

Tricyclic pyrazoles Part 7. Discovery of potent and selective dihydrothienocyclopentapyrazole derived CB2 ligands

Pinna, G;Curzu, Maria Michela;Dore, A;Ruiu, S;Pau, Amedeo;Murineddu, Gabriele;Pinna, Gerard Aime
2014

Abstract

A serie of dihydrothienocyclopentapyrazole-based derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The major term, the 6-methyl-1-(1,4-dichlorophenyl)-N-piperidinyl)- 1,4-dihydrothieno[20 ,30 -4,5]cyclopenta[1,2-c]pyrazole-3-carboxamide (6a), displayed a high affinity and good selectivity for CB2 receptors (Ki values of 2.30 nM for CB2 receptor and 440 nM for CB1 receptors respectively). Subsequent analogue preparation resulted in the identification of compounds such as 6b, 6d, 6e, 6k, 6l, 6m, 6s and 6t that showed 1.3e485 fold selectivity for CB2 receptors with potencies in the 1.1e7.2 nM range. These compounds profiled as full agonists at CB2 receptor in an inhibition assay of P- ERK 1/2 up regulation in HL-60 cells.
Tricyclic pyrazoles Part 7. Discovery of potent and selective dihydrothienocyclopentapyrazole derived CB2 ligands / Pinna, G; Curzu, Maria Michela; Dore, A; Lazzari, P; Ruiu, S; Pau, Amedeo; Murineddu, Gabriele; Pinna, Gerard Aime. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 85:(2014), pp. 747-757. [10.1016/j.ejmech.2014.08.042]
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: http://hdl.handle.net/11388/134340
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 8
social impact