Delving into the Latest Updates on ASP9436 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

PDE10A

Action

inhibitors

Mechanism

PDE10A inhibitors(Phosphodiesterase 10A inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Schizophrenia

Originator Organization

Astellas Pharma, Inc.

Active Organization-

Inactive Organization

Astellas Pharma, Inc.

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

We synthesized several biaryl derivatives as PDE10A inhibitors to prevent phototoxicity of 2-[4-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (1) and found that the energy difference between the energy-minimized conformation and the coplanar conformation of the biaryl moiety helped facilitate prediction of the phototoxic potential of biaryl compounds. Replacement of the quinoline ring of 1 with N-methyl benzimidazole increased this energy difference and prevented phototoxicity in the 3T3 NRU test. Further optimization identified 1-methyl-5-(1-methyl-3-{[4-(1-methyl-1H-benzimidazol-4-yl)phenoxy]methyl}-1H-pyrazol-4-yl)pyridin-2(1H)-one (38b). Compound 38b exhibited good selectivity against other PDEs, and oral administration of 38b improved visual-recognition memory deficit in mice at doses of 0.001 and 0.003mg/kg in the novel object recognition test. ASP9436 (sesquiphosphate of 38b) may therefore be used for the treatment of schizophrenia with a low risk of phototoxicity.

100 Deals associated with ASP9436

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