118183-22-5Relevant articles and documents
Certain phosphonic acids and derivatives
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, (2008/06/13)
The present invention is concerned with the compounds of formula I, wherein one or both of the acidic hydroxy groups of the phos-phonic acid moiety may be etherified, m reprensents one or zero, R1 is carboxy, esterified carboxy or amidated carboxy, wherein the five or six-membered heterocyclic ring may be additionally substituted on carbon and/or nitrogen, may have present a carbon-carbon double bond or may be fused on adjacent carbon atoms with a six-membered carbocyclic ring, A represents a direct bond or lower alkylene provided that A does not represent a direct bond when the heterocyclic ring together with substituent R1 represents 2-carboxypyr-rolidinyl; and salts thereof. These compounds are useful for the treatment of nervous system disorders in mammals and as antagonists of the N-methyl-D-aspartate sensitive excit-atory amino acid receptor.
Certain 2-carboxypiperidyl-(alkylene or alkenylene)-phosphonic acids and esters thereof useful for the treatment of disorders responsive to n-methyl-d-aspartate receptor blockade
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, (2008/06/13)
The present invention is concerned with the phosphonic acids of formula I STR1 wherein one or both of the acidic hydroxy groups of the phosphonic acid moiety may be functionalized in form of pharmaceutically acceptable mono- or di- esters; wherein Y represents optionally substituted 2-carboxypyrrolidinyl, 2-carboxy-2,5-dihydropyrrolyl, 2-carboxy-1,2,3,6-tetrahydropyridinyl, 2-carboxy-1,2,5,6-tetrahydropyridinyl, 2-carboxypiperidinyl, 2-carboxytetrahydroquinolinyl or 2-carboxyperhydroquinolinyl, 2-carboxy-2,3-dihydroindolyl or 2-carboxyperhydroindolyl as described herein, and in each of which the carboxy group may be functionalized in form of a pharmaceutically acceptable ester or amide; A represents a direct bond, lower alkenylene, lower alkylidene or lower alkylene provided that A does not represent a direct bond when Y represents 2-carboxypyrrolidinyl; and pharmaceutically acceptable salts thereof; which are useful for the treatment of nervous system disorders in mammals and as antagonists of the N-methyl-D-aspartate sensitive excitatory amino acid receptor.
4-(Phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids: Synthesis, activity at N-methyl-D-aspartic acid receptors, and anticonvulsant activity
Hutchison,Williams,Angst,De Jesus,Blanchard,Jackson,Wilusz,Murphy,Bernard,Schneider,Campbell,Guida,Sills
, p. 2171 - 2178 (2007/10/02)
A series of 4-(phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxyl acids were synthesized, and their biological activity was assessed as competitive ligands for the NMDA receptor, both in vitro by using a receptor binding assay [(3H]CGS 19755 binding) and in vivo by using an NMDA seizure model in mice. The analogues were also evaluated in [3H]AMPA and [3H]kainate binding to assess their affinity for non-NMDA excitatory amino acid receptor subtypes. A number of these analogues show potent and selective NMDA antagonistic activity both in vitro and in vivo. Most notable are 4-(phosphonomethyl)-2-piperidinecarboxylic acid (1a) (CGS 19755) and the phosphonopropenyl analogue 1i, both of which show anticonvulsant activity in the 1-2 mg/kg ip range. With the aid of computer-assisted modeling, a putative bioactive conformation for AP-5 is hypothesized from the SAR data presented and a preliminary model for the antagonist-preferring state of the NMDA receptor is presented.
