• Patchliner

    Most versatile automated patch clamp system on the market
  • Patchliner

    In-house production and QC of consumables
  • Patchliner

    More than 10 years experience in assay design and support
  • Dynamite8

    Automated Dynamic Clamp
  • Patchliner

    All features & benefits of manual patch clamp

2021 - Discovery and Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT4 Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer’s Disease

icon pl  Patchliner Publication in Journal of Medicinal Chemistry (2021)

Authors:
Nirogi R., Mohammed A. R., Shinde A. K., Gagginapally S. R., Kancharla D. M., Ravella S. R., Bogaraju N., Middekadi V. R., Subramanian R., Palacharla R. C., Benade V., Muddana N., Abraham R., Medapati R. B., Thentu J. B., Mekala V. R., Petlu S., Lingavarapu B. B., Yarra S., Kagita N., Goyal V. K., Pandey S. K., Jasti V.

Journal:

Journal of Medicinal Chemistry (2021) doi:10.1021/acs.jmedchem.1c00703


Abstract: 

A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer’s disease. Starting from a reported 5-HT4R antagonist, a systematic structure–activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-{5-[1-(3-methoxypropyl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate (Usmarapride, 12l). It showed balanced physicochemical–pharmacokinetic properties with robust nonclinical efficacy in cognition models. It also showed disease-modifying potential, as it increased neuroprotective soluble amyloid precursor protein alpha levels, and dose-dependent target engagement and correlation of efficacy with oral exposures. Phase 1 clinical studies have been completed and projected efficacious concentration was achieved without any major safety concerns. Phase 2 enabling long-term safety studies have been completed with no concerns for further development.


Download here

Back to Overview

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.