Antidepressant Agents. Derivatives of 2,3-Polymethyleneindoles¹

Abstract

A series of 1-substituted 2,3-polymethyleneindoles was prepared and examined for central nervous system activity. A number of these compounds wrere found to be active as antidepressants. The required 2,3-polymethyleneindoles were prepared by suitable modifications of the Fischer indole synthesis from arylhydrazines and alicyclic ketones. These were converted to N-substituted derivatives by various methods.

Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach

“…30 A fluorescence polarization (FP)-based competition assay was used to quantify inhibition of a LM-SC interaction by the four fragment hits. 30 In this assay, a fluorescently labeled SC-binding tracer peptide based on a LM derived from the consensus-binding motif (5-carboxyfluorescein-QLDLF, K d = 70 nM) 12,32,33 was used as the competitive probe ligand.…”

“…Searches of the ZINC library 35 (Table S3, Supporting Information) identified tetrahydrocarbazoles 7 and 8, which were found to have K i values of binding, highlighting the importance of the acid group. Eighteen additional tetrahydrocarbazoles were synthesized and evaluated using the FP assay but all showed poor SC binding affinities (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) , Table S3 and Scheme S1, Supporting Information).…”

“…Proteins that interact with the SC recognise a surface binding pocket that consists of two subsites (I and II), 6,12,13 with one pocket located on each of the SC monomers ( Figure 1). These protein binding partners interact with the SC using linear motifs (LMs) located on their surfaces.…”

“…30 Two classes of small molecules have previously been reported that bind to subsite I (K i >10 µM), but no antibacterial activities were provided for these compounds. 12,28 In this work, X-ray crystallography was used as a primary screen to identify fragment hits against the E. coli SC. Binding poses adopted by these hits were used in combination with chemo-informatics to guide subsequent inhibitor design, with several promising compounds being identified that bind to the SC, disrupt LM-SC interactions and inhibit SC-dependent DNA replication in vitro.…”

Synthesis of thieno- and benzocyclohepta[b]indoles: Gewald reaction and regioselective cycloaddition of acetylenic esters

“…[1][2][3][4][5][6] The antidepressant activity of cyclohepta[b]indole 7 has stimulated considerable interest and had been the starting point for the synthesis of a large number of polycyclic indole derivaties. [8][9][10] Alkaloids that feature an indole nucleus such as prenylated indoles, carbazoles, indoloquinoline and cyclohepta [b]indole alkaloids often exhibit biological activities such as e.g.…”