Enantiomerically Pure Indazole Bioisosteres of Ifenprodil and Ro 25-6981 as Negative Allosteric Modulators of NMDA Receptors with the GluN2B Subunit.

Administration of negative allosteric modulators of GluN2B subunit-containing NMDA receptors such as Ro 25-6981 () and ifenprodil () results in neuroprotective effects. In this study, the phenol of and was replaced bioisosterically by an indazole to inhibit glucuronidation. The γ- and β-aminoalcohols and were prepared without installing a protective group at the indazole ring using the ketone as a common intermediate.

Extensive red blood cell matching considering patient alloimmunization risk.

Background And Objectives: Red blood cell (RBC) transfusions pose a risk of alloantibody development in patients. For patients with increased alloimmunization risk, extended preventive matching is advised, encompassing not only the ABO-D blood groups but also the most clinically relevant minor antigens: C, c, E, e, K, Fy, Fy, Jk, Jk, S and s. This study incorporates patient-specific data and the clinical consequences of mismatching into the allocation process.

Negative allosteric modulators of NMDA receptors with GluN2B subunit: synthesis of β-aminoalcohols by epoxide opening and subsequent rearrangement.

In order to obtain novel antagonists of GluN2B subunit containing NMDA receptors, aryloxiranes were opened with benzylpiperidines. Phenyloxiranes 6 and (indazolyl)oxirane 15 were opened regioselectively at the position bearing the aryl moiety. Reaction of the resulting β-aminoalcohols 7 and 16 with carboxylic acids under Mitsunobu conditions (DIAD, PPh) led to rearrangement and after ester hydrolysis to the regioisomeric β-aminoalcohols 9 and 18.

Indazole as a Phenol Bioisostere: Structure-Affinity Relationships of GluN2B-Selective NMDA Receptor Antagonists.

Negative allosteric modulation of GluN2B subunit-containing NMDA receptors prevents overstimulation, resulting in neuroprotective effects. Since the phenol of prominent negative allosteric modulators is prone to rapid glucuronidation, its bioisosteric replacement by an indazole was envisaged. The key step in the synthesis was a Sonogashira reaction of non-protected iodoindazoles with propargylpiperidine derivatives.