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New Synthesis of Substituted 2‐Carboxyindole Derivatives: Versatile Introduction of a Carbamoylethynyl Moiety at the C‐3 Position
Author(s) -
Hewkin Cheryl T.,
Di Fabio Romano,
Conti Nadia,
Cugola Alfredo,
Gastaldi Paola,
Micheli Fabrizio,
Quaglia Anna M.
Publication year - 1999
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(19993)332:2<55::aid-ardp55>3.0.co;2-z
Subject(s) - moiety , chemistry , glycine , strychnine , stereochemistry , nmda receptor , in vivo , glycine receptor , chemical synthesis , in vitro , receptor , biochemistry , amino acid , biology , microbiology and biotechnology
A novel series of 3‐carbamoylethynyl‐2‐carboxyindoles, antagonists acting at the strychnine‐insensitive glycine binding site associated with the NMDA receptor, has been synthesised. This new versatile approach involves the introduction of a 2‐chloroethenyl moiety in position C‐3 with subsequent derivatisation of the terminal carboxyl group, followed by an unusual elimination of HCl to afford the ethynyl functionality. This novel series of glycine antagonists was evaluated in terms of in vitro affinity at the glycine binding site and the most potent compound was tested in vivo in the NMDA‐induced convulsions model in mice.