Tags

Type your tag names separated by a space and hit enter

Investigations on the 4-quinolone-3-carboxylic acid motif. 2. Synthesis and structure-activity relationship of potent and selective cannabinoid-2 receptor agonists endowed with analgesic activity in vivo.
J Med Chem. 2008 Aug 28; 51(16):5075-84.JM

Abstract

Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the range from 55.9 to 0.8 nM and CB1 affinity in the range from >10,000 to 5.3 nM, with selectivity indeces [Ki(CB1)/Ki(CB2)] varying from >2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity.

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 available

Pub Type(s)

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

Language

eng

PubMed ID

18680276

Citation

Pasquini, Serena, et al. "Investigations On the 4-quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure-activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed With Analgesic Activity in Vivo." Journal of Medicinal Chemistry, vol. 51, no. 16, 2008, pp. 5075-84.
Pasquini S, Botta L, Semeraro T, et al. Investigations on the 4-quinolone-3-carboxylic acid motif. 2. Synthesis and structure-activity relationship of potent and selective cannabinoid-2 receptor agonists endowed with analgesic activity in vivo. J Med Chem. 2008;51(16):5075-84.
Pasquini, S., Botta, L., Semeraro, T., Mugnaini, C., Ligresti, A., Palazzo, E., Maione, S., Di Marzo, V., & Corelli, F. (2008). Investigations on the 4-quinolone-3-carboxylic acid motif. 2. Synthesis and structure-activity relationship of potent and selective cannabinoid-2 receptor agonists endowed with analgesic activity in vivo. Journal of Medicinal Chemistry, 51(16), 5075-84. https://doi.org/10.1021/jm800552f
Pasquini S, et al. Investigations On the 4-quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure-activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed With Analgesic Activity in Vivo. J Med Chem. 2008 Aug 28;51(16):5075-84. PubMed PMID: 18680276.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigations on the 4-quinolone-3-carboxylic acid motif. 2. Synthesis and structure-activity relationship of potent and selective cannabinoid-2 receptor agonists endowed with analgesic activity in vivo. AU - Pasquini,Serena, AU - Botta,Lorenzo, AU - Semeraro,Teresa, AU - Mugnaini,Claudia, AU - Ligresti,Alessia, AU - Palazzo,Enza, AU - Maione,Sabatino, AU - Di Marzo,Vincenzo, AU - Corelli,Federico, Y1 - 2008/08/05/ PY - 2008/8/6/pubmed PY - 2008/9/11/medline PY - 2008/8/6/entrez SP - 5075 EP - 84 JF - Journal of medicinal chemistry JO - J Med Chem VL - 51 IS - 16 N2 - Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the range from 55.9 to 0.8 nM and CB1 affinity in the range from >10,000 to 5.3 nM, with selectivity indeces [Ki(CB1)/Ki(CB2)] varying from >2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity. SN - 1520-4804 UR - https://www.unboundmedicine.com/medline/citation/18680276/Investigations_on_the_4_quinolone_3_carboxylic_acid_motif__2__Synthesis_and_structure_activity_relationship_of_potent_and_selective_cannabinoid_2_receptor_agonists_endowed_with_analgesic_activity_in_vivo_ L2 - https://doi.org/10.1021/jm800552f DB - PRIME DP - Unbound Medicine ER -