Tags

Type your tag names separated by a space and hit enter

Investigations on the 4-quinolone-3-carboxylic acid motif. 3. Synthesis, structure-affinity relationships, and pharmacological characterization of 6-substituted 4-quinolone-3-carboxamides as highly selective cannabinoid-2 receptor ligands.
J Med Chem. 2010 Aug 26; 53(16):5915-28.JM

Abstract

A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting Ki>100 nM, all the quinolone-3-carboxamides 2 proved to be high affinity CB2 ligands, with Ki values ranging from 73.2 to 0.7 nM and selectivity [SI=Ki(CB1)/Ki(CB2)] varying from >14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI<1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonist-like behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors.

Authors+Show Affiliations

Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20718492

Citation

Pasquini, Serena, et al. "Investigations On the 4-quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure-affinity Relationships, and Pharmacological Characterization of 6-substituted 4-quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands." Journal of Medicinal Chemistry, vol. 53, no. 16, 2010, pp. 5915-28.
Pasquini S, Ligresti A, Mugnaini C, et al. Investigations on the 4-quinolone-3-carboxylic acid motif. 3. Synthesis, structure-affinity relationships, and pharmacological characterization of 6-substituted 4-quinolone-3-carboxamides as highly selective cannabinoid-2 receptor ligands. J Med Chem. 2010;53(16):5915-28.
Pasquini, S., Ligresti, A., Mugnaini, C., Semeraro, T., Cicione, L., De Rosa, M., Guida, F., Luongo, L., De Chiaro, M., Cascio, M. G., Bolognini, D., Marini, P., Pertwee, R., Maione, S., Di Marzo, V., & Corelli, F. (2010). Investigations on the 4-quinolone-3-carboxylic acid motif. 3. Synthesis, structure-affinity relationships, and pharmacological characterization of 6-substituted 4-quinolone-3-carboxamides as highly selective cannabinoid-2 receptor ligands. Journal of Medicinal Chemistry, 53(16), 5915-28. https://doi.org/10.1021/jm100123x
Pasquini S, et al. Investigations On the 4-quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure-affinity Relationships, and Pharmacological Characterization of 6-substituted 4-quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands. J Med Chem. 2010 Aug 26;53(16):5915-28. PubMed PMID: 20718492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigations on the 4-quinolone-3-carboxylic acid motif. 3. Synthesis, structure-affinity relationships, and pharmacological characterization of 6-substituted 4-quinolone-3-carboxamides as highly selective cannabinoid-2 receptor ligands. AU - Pasquini,Serena, AU - Ligresti,Alessia, AU - Mugnaini,Claudia, AU - Semeraro,Teresa, AU - Cicione,Lavinia, AU - De Rosa,Maria, AU - Guida,Francesca, AU - Luongo,Livio, AU - De Chiaro,Maria, AU - Cascio,Maria Grazia, AU - Bolognini,Daniele, AU - Marini,Pietro, AU - Pertwee,Roger, AU - Maione,Sabatino, AU - Di Marzo,Vincenzo, AU - Corelli,Federico, PY - 2010/8/20/entrez PY - 2010/8/20/pubmed PY - 2010/9/18/medline SP - 5915 EP - 28 JF - Journal of medicinal chemistry JO - J Med Chem VL - 53 IS - 16 N2 - A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting Ki>100 nM, all the quinolone-3-carboxamides 2 proved to be high affinity CB2 ligands, with Ki values ranging from 73.2 to 0.7 nM and selectivity [SI=Ki(CB1)/Ki(CB2)] varying from >14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI<1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonist-like behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors. SN - 1520-4804 UR - https://www.unboundmedicine.com/medline/citation/20718492/Investigations_on_the_4_quinolone_3_carboxylic_acid_motif__3__Synthesis_structure_affinity_relationships_and_pharmacological_characterization_of_6_substituted_4_quinolone_3_carboxamides_as_highly_selective_cannabinoid_2_receptor_ligands_ L2 - https://doi.org/10.1021/jm100123x DB - PRIME DP - Unbound Medicine ER -