Delving into the Latest Updates on GluN2B modulators(Janssen R&D) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

GluN2B

Action

modulators

Mechanism

GluN2B modulators(Glutamate [NMDA] receptor subunit epsilon 2 modulators)

Therapeutic Areas

Nervous System Diseases

Active Indication

Mood Disorders

Inactive Indication-

Originator Organization

Janssen R&D Ireland Ltd.

Active Organization

Janssen R&D Ireland Ltd.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC17H15F3N4O2S

InChIKeyVBYDZMQKWHOANY-UHFFFAOYSA-N

CAS Registry2222010-71-9

Author: Balana, Bartosz ; Coe, Kevin J. ; Jiang, Xiaohui ; Sepassi, Kia ; Needham, Alexandra S. ; Soyode-Johnson, Akinola ; Xia, Chungfang ; Schoellerman, Jeffrey ; Koudriakova, Tatiana ; Letavic, Michael A. ; Nguyen, Leslie ; Stenne, Brice ; Schoetens, Freddy ; Chrovian, Christa C. ; Scott, Brian ; Pippel, Daniel J. ; Lord, Brian

Selective inhibitors of the GluN2B subunit of N-methyl-d-aspartate receptors in the ionotropic glutamate receptor superfamily have been targeted for the treatment of mood disorders. We sought to identify structurally novel, brain penetrant, GluN2B-selective inhibitors suitable for evaluation in a clinical setting in patients with major depressive disorder. We identified a new class of negative allosteric modulators of GluN2B that contain a 1,3-dihydro-imidazo[4,5-b]pyridin-2-one core. This series of compounds had poor solubility properties and poor permeability, which was addressed utilizing two approaches. First, a series of structural modifications was conducted which included replacing hydrogen bond donor groups. Second, enabling formulation development was undertaken in which a stable nanosuspension was identified for lead compound 12. Compound 12 was found to have robust target engagement in rat with an ED₇₀ of 1.4 mg/kg. The nanosuspension enabled sufficient margins in preclinical toleration studies to nominate 12 for progression into advanced good laboratory practice studies.

100 Deals associated with GluN2B modulators(Janssen R&D)

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