title: Positive and negative modulation of group I metabotropic glutamate receptors.
abstract: A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as positive and negative mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homology model of the mGlu1 receptor was established, and a putative binding mode within the receptor's transmembrane domain was visualized.
authors.affiliation: Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Maksims
authors.initials: M
authors.lastname: Vanejevs
authors.forename: Claudia
authors.initials: C
authors.lastname: Jatzke
authors.forename: Steffen
authors.initials: S
authors.lastname: Renner
authors.forename: Sibylle
authors.initials: S
authors.lastname: Müller
authors.forename: Mirko
authors.initials: M
authors.lastname: Hechenberger
authors.forename: Tanja
authors.initials: T
authors.lastname: Bauer
authors.forename: Anna
authors.initials: A
authors.lastname: Klochkova
authors.forename: Ilya
authors.initials: I
authors.lastname: Pyatkin
authors.forename: Denis
authors.initials: D
authors.lastname: Kazyulkin
authors.forename: Elena
authors.initials: E
authors.lastname: Aksenova
authors.forename: Sergey
authors.initials: S
authors.lastname: Shulepin
authors.forename: Olga
authors.initials: O
authors.lastname: Timonina
authors.forename: Ariane
authors.initials: A
authors.lastname: Haasis
authors.forename: Aleksandrs
authors.initials: A
authors.lastname: Gutcaits
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Parsons
authors.forename: Valerjans
authors.initials: V
authors.lastname: Kauss
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
mesh_terms: D000114:Acetylene / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000494:Allosteric Regulation; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D006224:Cricetinae; D003412:Cricetulus; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D003517:Cyclopentanes; D018683:Excitatory Amino Acid Agents; D007295:Inositol Phosphates; D009570:Nitriles; D010879:Piperazines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D000114:Acetylene; D002118:Calcium