The synthesis and biological evaluation of quinolyl-piperazinyl piperidines as potent serotonin 5-HT1A antagonists

…, GT Grosu, Z Shen, MA Abou-Gharbia…

文献索引：Childers, Wayne E.; Havran, Lisa M.; Asselin, Magda; Bicksler, James J.; Chong, Dan C.; Grosu, George T.; Shen, Zhongqi; Abou-Gharbia, Magid A.; Bach, Alvin C.; Harrison, Boyd L.; Kagan, Natasha; Kleintop, Teresa; Magolda, Ronald; Marathias, Vasilios; Robichaud, Albert J.; Sabb, Annmarie L.; Zhang, Mei-Yi; Andree, Terrance H.; Aschmies, Susan H.; Beyer, Chad; Comery, Thomas A.; Day, Mark; Grauer, Steven M.; Hughes, Zoe A.; Rosenzweig-Lipson, Sharon; Platt, Brian; Pulicicchio, Claudine; Smith, Deborah E.; Sukoff-Rizzo, Stacy J.; Sullivan, Kelly M.; Adedoyin, Adedayo; Huselton, Christine; Hirst, Warren D. Journal of Medicinal Chemistry, 2010 , vol. 53, # 10 p. 4066 - 4084

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被引用次数: 6

摘要

As part of an effort to identify 5-HT1A antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT1A antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT1A antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SAR ...