65036-57-9Relevant articles and documents
HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 136, (2011/12/14)
Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes
Metabolism and disposition of 1,4,7,8-tetrachlorodibenzo-p-dioxin in rats
Huwe,Feil,Larsen,Wiener
, p. 1885 - 1893 (2007/10/03)
Metabolism studies of 1,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a relatively nontoxic dioxin congener, were undertaken to gain a better understanding of mammalian metabolism of dioxins without the problems associated with the use of the most toxic congener, 2,3,7,8-TCDD. 14C- 1,4,7,8-TCDD was dosed to conventional and bile-cannulated rats at a level of 8 mg/kg. The 14C was excreted almost entirely in 72 hours with the major routes of excretion feces and bile. Metabolites were identified from the feces, bile, and urine by GC-MS or negative ion FAB MS and 1H NMR. The two major fetal metabolites were hydroxylated tetra- and triCDDs. Glucuronide and sulfate conjugates of these hydroxyl metabolites were found in the urine and bile. Minor metabolites included dichlorocatechol, dihydroxylated tetra- and triCDDs, and conjugates of these compounds.
Potent Quinoxaline-Spaced Phosphono α-Amino Acids of the AP-6 Type as Competitive NMDA Antagonists: Synthesis and Biological Evaluation
Baudy, Reinhardt B.,Greenblatt, Lynne P.,Jirkovsky, Ivo L.,Conklin, Mary,Russo, Ralph J.,et al.
, p. 331 - 342 (2007/10/02)
A series of α-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a CPP binding assay.Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated TCP binding assay and in vivo by empolying an NMDA-induced seizure model.Some analogues also were evaluated in the -glycine binding assay.Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo.In particular α-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) d isplayed an ED50 of 1.1 mg/kg ip in the NMDA lethality model.Noteworthy is α-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 μM.
