Frolund, Bente; Jensen, Lars S.; Guandalini, Luca; Canillo, Carolina; Vestergaard, Henrik T.; Kristiansen, Uffe; Nielsen, Birgitte; Stensbol, Tine B.; Madsen, Christian; Krogsgaard-Larsen, Povl; Liljefors, Tommy published an article on January 27 ,2005. The article was titled 《Potent 4-Aryl- or 4-Arylalkyl-Substituted 3-Isoxazolol GABAA Antagonists: Synthesis, Pharmacology, and Molecular Modeling》, and you may find the article in Journal of Medicinal Chemistry.Electric Literature of C10H14N2O4 The information in the text is summarized as follows:
The 4-(2-naphthylmethyl)-5-(4-piperidyl)-3-hydroxyisoxazole I [R = 2-naphthylmethyl; (II)] showed higher affinity for the GABAA receptor site than the standard GABAA receptor antagonist, SR 95531. Mol. modeling studies of II exposed a cavity at the receptor recognition site capable of accommodating aromatic groups of substantial size in the 4-position in the isoxazole ring. Thus, a series of isoxazoles I (R = Ph, 1-naphthyl, 2-naphthyl, 1-bromo-2-naphthylmethyl, 1-phenylthio-2-naphthylmethyl, etc.) were synthesized as analogs of II and pharmacol. characterized using receptor-binding assays and electrophysiol. whole-cell patch-clamp techniques. All of the tested compounds show affinity for the GABAA receptor site. While I (R = 8-bromo-2-naphthylmethyl, 7-bromo-2-naphthylmethyl, 5-bromo-2-naphthylmethyl) showed receptor affinities (Ki = 45, 109, and 80 nM, resp.) comparable with that of II (Ki = 49 nM), I (R = 1-bromo-2-naphthylmethyl) provided the highest receptor affinity of the series (Ki = 10 nM). Introduction of a series of different substituents in the 1-position in the 2-naphthyl ring system led to compounds with retained high affinity for the GABAA receptor (Ki = 16-250 nM). Introduction of a Ph ring directly into the 4-position on the isoxazole ring gave a 41-fold increase in affinity relative to that of I (R = H). In whole-cell patch-clamp recordings from cultured cerebral cortical neurons, all of the tested compounds were able to inhibit the effect of the specific GABAA agonist isoguvacine, I (R = 1-bromo-2-naphthylmethyl) showing antagonist potency (IC50 = 42 nM) markedly higher than that of SR 95531 (IC50 = 240 nM). Mol. modeling studies, based on the compounds described, emphasized the importance of the distal ring in II for receptor affinity and the considerable dimensions of the proposed receptor cavity. Furthermore, the Ph rings in I (R = Ph, 1-phenyl-2-naphthylmethyl) were shown to represent highly favorable positions for an aromatic ring in previously unexplored receptor regions in terms of a pharmacophore model. In the experimental materials used by the author, we found Methyl 4-(3-hydroxyisoxazol-5-yl)piperidine-1-carboxylate(cas: 439944-71-5Electric Literature of C10H14N2O4)
Methyl 4-(3-hydroxyisoxazol-5-yl)piperidine-1-carboxylate(cas: 439944-71-5) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Electric Literature of C10H14N2O4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem