53764-72-0Relevant academic research and scientific papers
Drug efflux pump inhibitor
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, (2008/06/13)
A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R1 and R2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W1 represents —CH═CH—, —CH2O—, —CH2CH2— or the like; R3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R4 represents hydrogen atom, a group of —OZ0-4R5 (Z0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R5 represents a cyclic alkyl group, an aryl group or the like); W2 represents a single bond or —C(R8)═C(R9)— (R8 and R9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.
4-(Tetrazolylalkyl)piperidine-2-carboxylic Acids. Potent and Selective N-Methyl-D-aspartic Acid Receptor Antagonists with a Short Duration of Action
Ornstein, Paul L.,Schoepp, Darryle D.,Arnold, M. Brian,Leander, J. David,Lodge, David,et al.
, p. 90 - 97 (2007/10/02)
We have prepared a series of cis-4-(tetrazolylalkyl)piperidine-2-carboxylic acids as potent and selective N- methyl-D-aspartic acid (NMDA) receptor antagonists.NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia.The compounds prepared were evaluated in vitro in both receptor binding assays (CGS-19755, AMPA, and kainic acid) and in a cortical-wedge preparation (versus NMDA, quisqualic acid, and kainic acid) to determine affinity, potency, and selectivity.The new amino acids were also evaluated in vivo for their ability to block NMDA-induced convulsions in neonatal rats and NMDA-induced lethality in mice.The most potent compound of this series, 15 (LY233053), selectively displaced CGS-19755 binding with an IC50 of 107 +/- 7 nM and selectively antagonized responses due to NMDA in a cortical-wedge preparation with an IC50 of 4.2 +/- 0.4 μm.Compound 15 blocked both NMDA-induced convulsions in neonatal rats (minimum effective dose (MED) = 20 mg/kg ip) and NMDA-induced lethality in mice (MED = 5 mg/kg ip).This is the first example of an NMDA receptor antagonist that incorporates a tetrazole moiety as an ω-acid bioisostere.These amino acid antagonists are also unique from their phosphonic acid counterparts in that they have a shorter duration of action in vivo.For the treatment of acute disorders such as stroke, where an NMDA antagonist would be administered parenterally, the shorter duration of action may be beneficial, e.g., allowing for better dosage control.The combination of potent NMDA receptor antagonism and a short duration of action may make these compounds useful therapeutic agents in the treatment of a variety of neurological disorders.
