22468-26-4Relevant articles and documents
LINCOMYCIN DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY
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Page 114-115, (2010/02/06)
Novel lincomycin derivatives are disclosed. These lincomycin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against bacteria, including gram positive organisms, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
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.
