88147-56-2Relevant academic research and scientific papers
Improved synthetic route for the GluN2-specific NMDA receptor glycine site agonist AICP
Clausen, Rasmus P.,Hansen, Kasper B.,Rouzbeh, Nirvan,Zhao, Fabao
supporting information, (2020/02/04)
(R)-2-Amino-3-(4-(2-ethylphenyl)-1H-indole-2-carboxamido)propanoic acid (AICP) is a N-methyl-D-aspartate (NMDA) receptor glycine site agonist with unprecedented high potency in the low nanomolar range, and a GluN2 subunit-dependent pharmacological profile in terms of potency and agonist efficacy (Jessen et al., 2017 [1]). Here, we report a scalable, practical and cost-efficient synthetic route for AICP, which is an improvement compared to the previously reported route. This improved synthetic route includes a versatile diphenylmethylester (DPM) protection for the amino acid moiety, which can be widely used in the synthesis of other amino acid ligands. Further functional evaluation of AICP at the different ionotropic glutamate receptor (iGluR) classes demonstrates that high affinity binding of AICP to the orthosteric binding site is selective for NMDA receptors over AMPA and kainate receptors. Furthermore, high affinity binding of AICP is not observed at GluN3A, GluN3B, and GluD2 subunits, which also bind glycine and D-serine. Thus, the new approach described here enables scalable synthesis of AICP for the use as a pharmacological tool compound to study the involvement of neuronal NMDA receptor subtypes in normal brain function and disease.
NEW PENICILLINS FROM ISOPENICILLIN N SYNTHASE.
Baldwin, Jack E.,Bradley, Mark,Abbott, Shaun D.,Adlington, Robert M.
, p. 5309 - 5328 (2007/10/02)
The three tripeptides δ-L-α-aminoadipoyl-L-cysteinyl-D-propargylglycine, δ-L-α-aminoadipoyl-L-cysteinyl-D-cyanoalanine and δ-L-α-aminoadipoyl-L-cysteinyl-D--norvaline were synthesised and incubated with the enzyme Isopenicillin N Synthase (IPNS).All incubation mixtures contained biologically active products, and led to the isolation of four new penicillins (β-ethyl, α-acetylenic, α- and β-nitrile) following purification by reverse phase HPLC.The stereochemistries of formation of monosubstituted penicillins with IPNS are rationalised.
A total synthesis of nocardicins
Isenring,Hofheinz
, p. 2591 - 2597 (2007/10/02)
Four-component-condensation of D-isoserine or L-isoserine, diphenylmethyl isocyanide and p-(benzyloxy)benzaldehyde was used to construct a functionalized β-lactam ring system which was transformed in 4 steps into 3-aminocardicinic acid. A protected side c
