9H-Xanthene-9-carboxylic acid [1,2,4]oxadiazol-3-yl- and (2H-tetrazol-5-yl)-amides as potent, orally available mGlu1 receptor enhancers.
Small molecule mGluR1 enhancers based on the lead compound (9H-xanthene-9-carbonyl)-carbamic acid butyl ester derived from random-screening hit diphenylacetyl-carbamic acid ethyl ester were designed and synthesized as useful pharmacological tools for the study of the physiological roles mediated by mGlu1 receptors. The synthesis and the structure-activity relationship of this new class of positive allosteric modulators of mGlu1 receptors will be discussed in detail.
Vieira
Eric
E
Pharma Division, Discovery Research, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. eric.vieira@roche.com
Huwyler
Jörg
J
Jolidon
Synèse
S
Knoflach
Frédéric
F
Mutel
Vincent
V
Wichmann
Jürgen
J
D000494:Allosteric Regulation; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010069:Oxadiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013050:Spectrometry, Fluorescence; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D010069:Oxadiazoles; D018094:Receptors, Metabotropic Glutamate; D013777:Tetrazoles; C104077:metabotropic glutamate receptor type 1