A5040843846- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Pharmacological Receptor Mechanisms and Effects
- Cancer Treatment and Pharmacology
- Chemical Synthesis and Reactions
- Mass Spectrometry Techniques and Applications
- Synthesis and pharmacology of benzodiazepine derivatives
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical synthesis and alkaloids
- Nicotinic Acetylcholine Receptors Study
- Synthetic Organic Chemistry Methods
- Ion channel regulation and function
- Analytical Chemistry and Chromatography
- Marine Sponges and Natural Products
- Peptidase Inhibition and Analysis
- Molecular Sensors and Ion Detection
- Crystallography and molecular interactions
- Animal Ecology and Behavior Studies
- Marine Toxins and Detection Methods
- Botany and Plant Ecology Studies
- Ecology and biodiversity studies
- Synthesis and Biological Activity
Eli Lilly (United States)
2004-2018
Colorado State University
1995-1996
As part of our ongoing research to identify novel agents acting at metabotropic glutamate 2 (mGlu2) and 3 (mGlu3) receptors, we have previously reported the identification C4α-methyl analog mGlu2/3 receptor agonist 1 (LY354740). This molecule, 1S,2S,4R,5R,6S-2-amino-4-methylbicyclo[3.1.0]hexane-2,6-dicarboxylate (LY541850), exhibited an unexpected mGlu2 agonist/mGlu3 antagonist pharmacological profile, whereas C4β-methyl diastereomer (3) possessed dual activity. We now further explored this...
Identification of orthosteric mGlu(2/3) receptor agonists capable discriminating between individual mGlu2 and mGlu3 subtypes has been highly challenging owing to the glutamate-site sequence homology these proteins. Herein we detail preparation characterization a series molecules related (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate 1 (LY354740) bearing C4-thiotriazole substituents. On basis second messenger responses in cells expressing other recombinant human mGlu2/3 subtypes,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric Synthesis of the Key Intermediates Leading to (-)-Aphanorphine and (-)-EptazocineAlison N. Hulme, Steven S. Henry, A. I. MeyersCite this: J. Org. Chem. 1995, 60, 5, 1265–1270Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/jo00110a033https://doi.org/10.1021/jo00110a033research-articleACS PublicationsRequest reuse permissionsArticle...
(-)-4-Amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate (LY389795, (-)-3) is a highly potent and selective agonist of metabotropic glutamate receptors 2 (mGlu2) 3 (mGlu3). As part our ongoing research program, we have prepared S-oxidized variants (-)-3, compounds (-)-10, (+)-11 (LY404040), (-)-12 (LY404039). Each these chiral heterobicyclic amino acids displaced specific binding the mGlu2/3 receptor antagonist 3H-2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoic acid...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis strategies for marine diterpenes. Total synthesis of the clavularanesDavid R. Williams, Paul J. Coleman, and Steven S. HenryCite this: Am. Chem. Soc. 1993, 115, 24, 11654–11655Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/ja00077a097https://doi.org/10.1021/ja00077a097research-articleACS PublicationsRequest reuse permissionsArticle...
Multiple therapeutic opportunities have been suggested for compounds capable of selective activation metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking. As part our ongoing efforts to identify potent, selective, and systemically bioavailable agonists mGlu2 mGlu3 receptor subtypes, a series C4β-N-linked variants (1S,2S,5R,6S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared evaluated both binding affinity functional cellular...
As part of our ongoing interest in identifying novel agonists acting at metabotropic glutamate (mGlu) 2/3 receptors, we have explored the effect structural modifications 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate (LY354740), a potent and pharmacologically balanced mGlu2/3 receptor agonist. Incorporation relatively small substituents (e.g., F, O) C4 position this molecule resulted additional highly that demonstrate excellent selectivity over other mGlu subtypes, while addition...
An efficient and divergent synthesis of C4α- C4β-methyl-substituted analogues 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate, which are important tools in the study metabotropic glutamate receptor function, has been achieved. By taking advantage an unanticipated facial selectivity bicyclo[3.1.0]hexane ring system, either or C4β-methyl substituent was introduced a highly stereoselective high-yielding manner.
Abstract An operationally simple method is presented for the conversion of fully protected amino acids to completely unprotected parent compounds including mixed mGlu2 agonist/mGlu3 antagonist (IV).
Abstract For see ChemInform in Full Text.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”