166599-76-4Relevant articles and documents
3-Indolyl-1-naphthylmethanes: New cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB1 cannabinoid receptor
Huffman, John W.,Mabon, Ross,Wu, Ming-Jung,Lu, Jianzhong,Hart, Richard,Hurst, Dow P.,Reggio, Patricia H.,Wiley, Jenny L.,Martin, Billy R.
, p. 539 - 549 (2007/10/03)
A series of 1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (9-11) and 2-methyl-1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (12-14) have been synthesized to investigate the hypothesis that cannabimimetic 3-(1-naphthoyl)indoles interact with the CB1 receptor by hydrogen bonding to the carbonyl group. Indoles 9-11 have significant (Ki=17-23 nM) receptor affinity, somewhat less than that of the corresponding naphthoylindoles (5, 15, 16). 2-Methyl-1-indoles 12-14 have little affinity for the CB1 receptor, in contrast to 2-methyl-3-(1-naphthoyl)indoles 17-19, which have affinities comparable to those of 5, 15, 16. A cannabimimetic indene hydrocarbon (26) was synthesized and found to have Ki=26±4 nM. Molecular modeling and receptor docking studies of naphthoylindole 16, its 2-methyl congener (19) and indolyl-1-naphthylmethanes 11 and 14, combined with the receptor affinities of these cannabimimetic indoles, strongly suggest that these cannabinoid receptor ligands bind primarily by aromatic stacking interactions in the transmembrane helix 3-4-5-6 region of the CB1 receptor.
