Mapping the melatonin receptor. 2. synthesis and biological activity of indole derived melatonin analogues with restricted conformations of the C-3 amidoethane side chain

Bioorganic & Medicinal Chemistry Letters
1994.0

Abstract

A number of indole derived melatonin analogues have been prepared with the C-3 amidoethane side chain partially constrained by incorporation in a ring. The biological achvity has been correlated with the conformation of the "side chain", the nature of the N-acylating group, and the spatial distance between the methoxyl and amide functions.The pineal hormone melatonin (la) plays a major role in the regulation of seasonal cycles and the control of circadran rhythms'** and has been the focus of considerable clinical interest3 As part of a programme to map the melatonrn receptor by examrning the spahal and electronrc restnctions that it imposes on melatonin anafogues for them stall to act as agonrsts4 we have synthesised a number of mdoles annelated on the [b] face of the pyrrole moiety. Such compounds have constrained or partially constrained conformations of the C-3 amidoethane side chain. We chose indole as the basis for our model system in order to minimrse deviations from the natural melatonin structure, since we were also concerned with the relative spatial arrangement of this side chain and the methoxyl group at a position equrvalent to C-5 in melatonin We now report the preparation and biological activity of a number of N-acyl-9amino-1,2.3,4-tetrahydrocarbabazoles and N-acyl-4-ammomethyl-9-methyl-l ,2,3,4-tetrahydrocarbazoles.5

Knowledge Graph

Similar Paper

Mapping the melatonin receptor. 2. synthesis and biological activity of indole derived melatonin analogues with restricted conformations of the C-3 amidoethane side chain
Bioorganic & Medicinal Chemistry Letters 1994.0
Conformationally Restrained Melatonin Analogues:  Synthesis, Binding Affinity for the Melatonin Receptor, Evaluation of the Biological Activity, and Molecular Modeling Study
Journal of Medicinal Chemistry 1997.0
1-(2-Alkanamidoethyl)-6-methoxyindole Derivatives:  A New Class of Potent Indole Melatonin Analogues
Journal of Medicinal Chemistry 1997.0
Indole-based melatonin analogues: Synthetic approaches and biological activity
European Journal of Medicinal Chemistry 2020.0
Mapping the Melatonin Receptor. 3. Design and Synthesis of Melatonin Agonists and Antagonists Derived from 2-Phenyltryptamines
Journal of Medicinal Chemistry 1995.0
Mapping the Melatonin Receptor. 5. Melatonin Agonists and Antagonists Derived from Tetrahydrocyclopent[b]indoles, Tetrahydrocarbazoles and Hexahydrocyclohept[b]indoles
Journal of Medicinal Chemistry 1998.0
Design and synthesis of 1-(2-alkanamidoethyl)-6-methoxy-7-azaindole derivatives as potent melatonin agonists
Bioorganic & Medicinal Chemistry Letters 2011.0
Mapping the melatonin receptor. 1. the 5-methoxyl group of melatonin is not an essential requirement for biological activity
Bioorganic & Medicinal Chemistry Letters 1994.0
2-[N-Acylamino(C<sub>1</sub>−C<sub>3</sub>)alkyl]indoles as MT<sub>1</sub> Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists
Journal of Medicinal Chemistry 1998.0
Synthesis of a Novel Series of Benzocycloalkene Derivatives as Melatonin Receptor Agonists
Journal of Medicinal Chemistry 2002.0