Design, synthesis, and pharmacological evaluation of 5-oxo-1,2,4-oxadiazole derivatives as AT₁ antagonists with antihypertension activities

ABSTRACT

A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT₁ receptor at the same order of magnitude to losartan. The methyl ester with 1, 4-disubsituted indole group, 1 (5.01 ± 1.67 nM) showed high antihypertension activity on spontaneously hypertensive rats (SHRs). Its maximal response lowered 30 mmHg of mean blood pressure (MBP) at 10 mg/kg after oral administration, which was better than irbesartan, and the antihypertensive effect lasted beyond 24 h. These results made 1 deserve further investigation.

KEYWORDS:

• Antihypertension
• AT₁ antagonists
• 5-oxo-1
• -oxadiazole
• N-phenyl indole
• acute toxicity

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This work was supported by Foundation of Science and Technology Commission of Shanghai (Grant No. 13431900700, 14431906200), Foundation of Donghua University (Grant No. 14D110906), and Foundation of Ningbo Science & Technology Bureau (Grant No. 2015A610274).

Supplemental data

Supplemental data for this article can be accessed on the publisher's website at http://dx.doi.org/10.3109/10641963.2016.1151527.

Additional information

Funding

This work was supported by Foundation of Science and Technology Commission of Shanghai (Grant No. 13431900700, 14431906200), Foundation of Donghua University (Grant No. 14D110906), and Foundation of Ningbo Science & Technology Bureau (Grant No. 2015A610274).