Biomaterial Database

Design and synthesis of a novel series of 1,2-disubstituted cyclopentanes as small, potent potentiators of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors. 2002

Timothy A Shepherd, and James A Aikins, and David Bleakman, and Buddy E Cantrell, and John P Rearick, and Richard L Simon, and Edward C R Smith, and Gregory A Stephenson, and Dennis M Zimmerman, and Allan Mandelzys, and Keith R Jarvie, and Ken Ho, and Michelle Deverill, and Rajender K Kamboj

NPS Allelix Corporation, 6850 Goreway Drive, Mississaugua, Ontario L4V 1V7, Canada. Shepherd_Timothy@Lilly.com

2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) potentiators are ligands that act as positive allosteric modulators at the AMPA receptors. We recently disclosed a novel series of 2-arylpropylsulfonamides that were potent potentiators of responses mediated through AMPA receptors. To further define the structural requirements for activity in this series, new ring-constrained analogues were prepared and a new stereocenter was introduced. The potentiating activity was highly dependent on the stereochemistry at the 2-position of the disubstituted cyclopentane and was independent of the relative stereochemistry at the 1-position. Compound (R,R)-10 represents a potent, novel potentiator of iGluR4 flip receptors (EC(50) = 22.6 nM).

UI	MeSH Term	Description	Entries
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003517	Cyclopentanes	A group of alicyclic hydrocarbons with the general formula R-C5H9.	Cyclopentadiene,Cyclopentadienes,Cyclopentene,Cyclopentenes,Cyclopentane
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013449	Sulfonamides	A group of compounds that contain the structure SO2NH2.	Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D018091	Receptors, AMPA	A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).	AMPA Receptors,Quisqualate Receptors,AMPA Receptor,Quisqualate Receptor,Receptor, AMPA,Receptor, Quisqualate,Receptors, Quisqualate
D018683	Excitatory Amino Acid Agents	Drugs used for their actions on any aspect of excitatory amino acid neurotransmitter systems. Included are drugs that act on excitatory amino acid receptors, affect the life cycle of excitatory amino acid transmitters, or affect the survival of neurons using excitatory amino acids.	Amino Acids, Excitatory, Agents,Glutamate Agents,Agents, Excitatory Amino Acid,Amino Acid Agents, Excitatory,EAA Agents,Excitatory Amino Acid Effect,Excitatory Amino Acid Effects,Glutamatergic Agents,Agents, EAA,Agents, Glutamate,Agents, Glutamatergic
D018698	Glutamic Acid	A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.	Aluminum L-Glutamate,Glutamate,Potassium Glutamate,D-Glutamate,Glutamic Acid, (D)-Isomer,L-Glutamate,L-Glutamic Acid,Aluminum L Glutamate,D Glutamate,Glutamate, Potassium,L Glutamate,L Glutamic Acid,L-Glutamate, Aluminum