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  3. Design, synthesis and biological evaluation of novel indole-3-carboxylic acid derivatives with antihypertensive activity

Design, synthesis and biological evaluation of novel indole-3-carboxylic acid derivatives with antihypertensive activity

  • Bioorg Med Chem Lett. 2023 Jun 15;90:129349. doi: 10.1016/j.bmcl.2023.129349.
Andrey V Danilenko 1,  Alexander N Volov 2,  Nikolai A Volov 3,  Yana B Platonova 1,  Serguei V Savilov 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Lomonosov Moscow State University, 1 Leninskie Gory, Moscow 119991, Russian Federation.
  • 2 Department of Chemistry, Lomonosov Moscow State University, 1 Leninskie Gory, Moscow 119991, Russian Federation. Electronic address: [email protected].
  • 3 Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, Russian Federation.
  • 4 Department of Chemistry, Lomonosov Moscow State University, 1 Leninskie Gory, Moscow 119991, Russian Federation; Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 31 Leninsky prospect, Moscow 119071, Russian Federation.
PMID: 37236375 DOI: 10.1016/j.bmcl.2023.129349
Abstract

Molecular design, synthesis, in vitro and in vivo studies of novel derivatives of indole-3-carboxylic acid new series of angiotensin II receptor 1 antagonists is presented. Radioligand binding studies using [125I]-angiotensin II displayed that new derivatives of indole-3-carboxylic acid have a high nanomolar affinity for the angiotensin II receptor (AT1 subtype) on a par with the known pharmaceuticals such as losartan. Biological studies of synthesized compounds in spontaneously hypertensive rats have demonstrated that compounds can lower blood pressure when administered orally. Maximum the decrease in blood pressure was 48 mm Hg with oral administration of 10 mg/kg and antihypertensive effect was observed for 24 h, which is superior to losartan.

Keywords

Angiotensin II receptor 1 antagonist; Antihypertension drug; Hypertension; Indole-3-carboxylic acid.

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