83732-75-6Relevant articles and documents
Novel fused pyrrole heterocyclic ring systems as structure analogs of LE 300: Synthesis and pharmacological evaluation as serotonin 5-HT2A, dopamine and histamine H1 receptor ligands
Rostom, Sherif A. F.
, p. 73 - 80 (2010)
LE 300 represents a structurally novel type of antagonists acting preferentially at the dopamine D1/D5 receptors and the serotonin 5-HT2A receptor. This compound consists of a ten-membered central azecine ring fused to an indole ring on one side and a benzene moiety on the other side. To estimate the importance of the indole and / or phenyl moieties in this highly active benzindolo-azecine, both rings were removed and replaced with a 1H-pyrrole counterpart. Accordingly, some new analogs of LE 300 namely, pyrrolo[2,3-g]indolizine, pyrrolo[3,2-a]quinolizine rings and their corresponding dimethylpyrrolo[2,3-d]azonine, and dimethylpyrrolo[2,3-d]azecine were synthesized to be evaluated for their activity at the 5-HT2A and dopamine D1, D2L, D4, D5 receptors in relation to LE 300. In addition, their activity at the H1-histamine receptors was also determined. The results suggested that the rigid pyrrolo[2,3-g] indolizine 7 and pyrrolo[3,2-a]quinolizine 8 analogs lacked biological activity in the adopted three bioassays. However, their corresponding flexible pyrrolo[2,3-d]azonine 11 and pyrrolo[2,3-d]azecine 12 derivatives revealed weak partial agonistic activity and weak antagonistic potency at the serotonin 5-HT2A and histamine H1 receptors, respectively. Meanwhile, they showed no affinity to any of the four utilized dopamine receptors. Variation in ring size did not contribute to a significant influence on the three tested bioactivities. Removal of the hydrophobic moiety (phenyl ring) and replacement of the indole moiety with a 1H-pyrrole counterpart led to a dramatic alteration in the profile of activity of such azecine-type compounds.
Diastereodivergent pictet-spengler cyclization of bicyclic N-acyliminium ions: Controlling a quaternary stereocenter
De Carn-Carnavalet, Benot,Krieger, Jean-Philippe,Follas, Benot,Brayer, Jean-Louis,Demoute, Jean-Pierre,Meyer, Christophe,Cossy, Janine
supporting information, p. 1273 - 1282 (2015/03/04)
The diastereoselectivity of the Pictet-Spengler cyclization of bicyclic N-acyliminium ions that contain a 3-azabicyclo-[n.3.0]alkane core and an electron-rich ?-nucleophilic moiety, such as an indol-2-yl, indol-3-yl, 1-methylpyrrol-2-yl, or 3,5-dimethoxyphenyl group, was examined. The N-acyliminium ions were generated by protonation of the corresponding enamides or hemiaminals, which were derived from imides. Control of the quaternary stereocenter created at the newly formed ring junction was achieved in a diastereodivergent manner by fine-tuning the reaction conditions, which determined whether the reaction proceeded under kinetic or thermodynamic control. Mechanistic studies indicated that a retro-Pictet-Spengler reaction pathway is involved in the equilibration process.
Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors
Khorana, Nantaka,Smith, Carol,Herrick-Davis, Kathy,Purohit, Anil,Teitler, Milt,Grella, Brian,Dukat, Ma?gorzata,Glennon, Richard A.
, p. 3930 - 3937 (2007/10/03)
On the basis of an earlier finding that 5-methyl-5H-1,2,3,4-tetrahydropyrido[4,3-b]indole (5-methyl-1,2,3,4-tetrahydro-γ-carboline; 1) binds at murine 5-HT 5A receptors, preliminary structure-affinity studies were conducted. The present investigation extends these structure-affinity studies using human 5-HT5A receptors and examined additional analogues of 1. It was found (a) that there is little interspecies difference for the affinities of these compounds, (b) that an intact 1,2,3,4-tetrahydro-γ-carboline ring system seems optimal and an N2-(3-(substituted-phenoxy)propyl) moiety results in high affinity, (c) that structurally related 1,2,3,4-tetrahydro-β-carbolines also bind at 5-HT5A receptors, and (d) that all examined derivatives also possess affinity for 5-HT 2A receptors. Evidence is provided that 5-HT5A and 5-HT2A receptor affinities probably do not covary and that it might be possible, with continued investigation, to develop analogues with enhanced 5-HT5A selectivity.
