2. Academic Validation
  3. Discovery and Characterization of RGH-122, a Potent, Selective, and Orally Bioavailable V1a Receptor Antagonist

Discovery and Characterization of RGH-122, a Potent, Selective, and Orally Bioavailable V1a Receptor Antagonist

  • J Med Chem. 2024 Jan 11;67(1):643-673. doi: 10.1021/acs.jmedchem.3c01868.
Ferenc Baska 1,  Éva Bozó 1,  Zsolt Szeleczky 1,  Gábor Szántó 1,  Krisztina Vukics 1,  Zoltán Szakács 1,  Katalin Domány-Kovács 1,  Dalma Kurkó 1,  Elemér Vass 2,  Márta Thán 1,  Mónika Vastag 1,  Krisztina Temesvári 1,  Sándor Lévai 1,  Attila Sándor Halász 1,  Krisztina Szondiné Kordás 1,  Viktor Román 1,  István Greiner 1,  Imre Bata 1
Affiliations

Affiliations

  • 1 Gedeon Richter Plc, PO Box 27, Budapest H-1475, Hungary.
  • 2 Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest H-1117, Hungary.
PMID: 38165765 DOI: 10.1021/acs.jmedchem.3c01868
Abstract

The V1a receptor is a major contributor in mediating the social and emotional effects of arginine-vasopressin (AVP); therefore it represents a promising target in the treatment of several neuropsychiatric conditions. The aim of this research was to design and synthesize novel and selective V1a antagonists with improved in vitro and in vivo profiles. Through optimization and detailed SAR studies, we developed low nanomolar antagonists, and further characterizations led to the discovery of the clinical candidate compound 43 (RGH-122). The CNS activity of the compound was determined in a 3-chamber social preference test of autism in which RGH-122 successfully enhanced social preference with the lowest effective dose of 1.5 mg/kg.

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