2. Academic Validation
  3. New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists

New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists

  • J Med Chem. 2008 Dec 25;51(24):8124-34. doi: 10.1021/jm8008162.
Christopher M Yea 1,  Christine E Allan,  Doreen M Ashworth,  James Barnett,  Andy J Baxter,  Janice D Broadbridge,  Richard J Franklin,  Sally L Hampton,  Peter Hudson,  John A Horton,  Paul D Jenkins,  Andy M Penson,  Gary R W Pitt,  Pierre Rivière,  Peter A Robson,  David P Rooker,  Graeme Semple,  Andy Sheppard,  Robert M Haigh,  Michael B Roe
Affiliations

Affiliation

  • 1 Vantia Ltd, Southampton Science Park, Southampton SO16 7NP, United Kingdom. [email protected]
PMID: 19053774 DOI: 10.1021/jm8008162
Abstract

Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.

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