Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents.
作者： Claudia Vergelli , Giovanna Ciciani , Agostino Cilibrizzi , Letizia Crocetti , Lorenzo Di Cesare Mannelli
DOI: 10.1016/J.BMC.2015.08.043
关键词:
摘要: A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]-5-vinylpyridazin-3(2H)-one) was synthesized tested for their antinociceptive activity in Writhing Test. Many compounds, at doses 20-40 mg/kg po were able reduce abdominal constrictions by more than 47% and, same cases, potency is comparable as 5e, 24a, 27b 27c. The analgesia induced active compounds completely prevented pretreatment with α2-antagonist yohimbine, confirming involvement adrenergic system mechanism action these new compounds.
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sci-hub.se 参考文章(31)
Petpiboon Prasit, Denis Riendeau, Chapter 21. Selective Cyclooxygenase-2 Inhibitors Annual Reports in Medicinal Chemistry. ,vol. 32, pp. 211- 220 ,(1997) , 10.1016/S0065-7743(08)61479-7
Maria Paola Giovannoni, Claudia Vergelli, Carla Ghelardini, Nicoletta Galeotti, Alessandro Bartolini, Vittorio Dal Piaz, [(3-Chlorophenyl)piperazinylpropyl]pyridazinones and analogues as potent antinociceptive agents. Journal of Medicinal Chemistry. ,vol. 46, pp. 1055- 1059 ,(2003) , 10.1021/JM021057U
Stefano Pieretti, Vittorio Dal Piaz, Rosanna Matucci, Maria Paola Giovannoni, Alessandro Galli, Antinociceptive activity of a 3(2H)-pyridazinone derivative in mice Life Sciences. ,vol. 65, pp. 1381- 1394 ,(1999) , 10.1016/S0024-3205(99)00377-X
Claudia Vergelli, Maria Paola Giovannoni, Stefano Pieretti, Amalia Di Giannuario, Vittorio Dal Piaz, Pierfrancesco Biagini, Claudio Biancalani, Alessia Graziano, Nicoletta Cesari, 4-Amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive agents: Synthesis, SARs, and preliminary studies on the mechanism of action. Bioorganic & Medicinal Chemistry. ,vol. 15, pp. 5563- 5575 ,(2007) , 10.1016/J.BMC.2007.05.035
Maria Paola Giovannoni, Nicoletta Cesari, Claudia Vergelli, Alessia Graziano, Claudio Biancalani, Pierfrancesco Biagini, Carla Ghelardini, Elisa Vivoli, Vittorio Dal Piaz, 4-amino-5-substituted-3(2H)-pyridazinones as orally active antinociceptive agents: synthesis and studies on the mechanism of action. Journal of Medicinal Chemistry. ,vol. 50, pp. 3945- 3953 ,(2007) , 10.1021/JM070161E
Y. Lecrubier, MILNACIPRAN : THE CLINICAL PROPERTIES OF A SELECTIVE SEROTONIN AND NORADRENALINE REUPTAKE INHIBITOR (SNRI) Human Psychopharmacology-clinical and Experimental. ,vol. 12, ,(1997) , 10.1002/(SICI)1099-1077(199709)12:3+<S127::AID-HUP943>3.0.CO;2-X
Steven B Abramson, Jeffrey D Greenberg, Are NSAIDs and selective cyclo-oxygenase 2 inhibitors associated with increased risk of myocardial infarction? Nature Reviews Rheumatology. ,vol. 4, pp. 182- 183 ,(2008) , 10.1038/NCPRHEUM0763
John A. Butera, Current and emerging targets to treat neuropathic pain. Journal of Medicinal Chemistry. ,vol. 50, pp. 2543- 2546 ,(2007) , 10.1021/JM061015W
Ian Gilron, Anthony H Dickenson, Emerging drugs for neuropathic pain Expert Opinion on Emerging Drugs. ,vol. 19, pp. 329- 341 ,(2014) , 10.1517/14728214.2014.915025
Frank Andersohn, Samy Suissa, Edeltraut Garbe, Use of First- and Second-Generation Cyclooxygenase-2–Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction Circulation. ,vol. 113, pp. 1950- 1957 ,(2006) , 10.1161/CIRCULATIONAHA.105.602425