TY - JOUR
T1 - Synthesis and preliminary screening of novel indole-3-methanamines as 5-HT4 receptor ligands
AU - Hanna-Elias, Amir
AU - Manallack, David Thomas
AU - Berque-Bestel, I
AU - Irving, Helen Ruth
AU - Coupar, Ian Michael
AU - Iskander, Magdy Naguib
PY - 2009
Y1 - 2009
N2 - Twenty-three indole-3-methanamines were designed, synthesized and evaluated as ligands for the 5-HT4 receptor. Compounds I-d, I-J, I-o, I-q and I-u showed good affinity at 100 mu M and I-o was found to be only 5-fold less potent than the agonists serotonin (1) and 5-methoxytryptamine (2). Substitution on the 3-methanamine nitrogen clearly influenced activity with docking experiments into a homology model of the 5-HT4 receptor showing a range of interactions with these side chain substituents. This modelling work together with the SAR determined in this study has provided promising ideas for future synthetic work. (C) 2009 Elsevier Masson SAS. All rights reserved.
AB - Twenty-three indole-3-methanamines were designed, synthesized and evaluated as ligands for the 5-HT4 receptor. Compounds I-d, I-J, I-o, I-q and I-u showed good affinity at 100 mu M and I-o was found to be only 5-fold less potent than the agonists serotonin (1) and 5-methoxytryptamine (2). Substitution on the 3-methanamine nitrogen clearly influenced activity with docking experiments into a homology model of the 5-HT4 receptor showing a range of interactions with these side chain substituents. This modelling work together with the SAR determined in this study has provided promising ideas for future synthetic work. (C) 2009 Elsevier Masson SAS. All rights reserved.
UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science?_ob=ArticleURL&_udi=B6VKY-4VFK7P7-1&_user=542840&_coverDate=07%2F31%2F2009&_rdoc=1&_fmt
M3 - Article
SN - 0223-5234
VL - 44
SP - 2952
EP - 2959
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 7
ER -