title: 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.
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Zhu
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Bao
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: Pingyong
authors.initials: P
authors.lastname: Liao
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: b Department of Pharmacology , Shanghai Xianhui Pharmaceutical Co., Ltd , Shanghai , China.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Yan
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000188:drug therapy*; D000077405:Irbesartan; D019808:Losartan / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010069:Oxadiazoles; D013777:Tetrazoles; C521273:azilsartan; D000077405:Irbesartan; D019808:Losartan
keywords: -oxadiazole; 5-oxo-1; AT1 antagonists; Antihypertension; N-phenyl indole; acute toxicity