Synthesis and pharmacological evaluation of a novel AT1 angiotensin II receptor antagonist with anti-hypertension and anti-tumor effects.
A new compound 2-(4-((2-butyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl) benzamide (1) was designed, synthesized and evaluated as a novel AT1 receptor antagonist. Compound 1 displayed high affinity to AT1 receptor with an IC50 value of 1.65 ± 0.2 nM in radio-ligand binding assays. It had an efficient and long-lasting effect in reducing blood pressure which could last for more than 12 h at the dose of 10 mg/kg in spontaneously hypertensive rats. Acute toxicity tests suggested that compound 1 was safe with the LD50 value of 2519.81 mg/kg. Besides, in vitro and in vivo tests suggested its anti-proliferative and anti-tumor activities, respectively. So compound 1 could be considered as a novel anti-hypertension, anti-tumor candidate and deserved further investigation.
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Xiaolu
X
Bao
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Weibo
W
Zhu
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Yajing
Y
Da
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Linfeng
L
Zhu
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Li
L
Qie
b Shanghai Xianhui Pharmaceutical Co., Ltd. , Shanghai , China.
Yijia
Y
Yan
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Li
L
Wang
b Shanghai Xianhui Pharmaceutical Co., Ltd. , Shanghai , China.
Hesheng
H
Tang
a Department of Pharmaceutical Science and Technology , College of Chemistry and Biology, Donghua University , Shanghai , China and.
Zhi-long
ZL
Chen
D057911:Angiotensin Receptor Antagonists / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR
D057911:Angiotensin Receptor Antagonists; D001549:Benzamides; C037689:benzamide
Angiotensin II receptor antagonist; anti-hypertension; anti-tumor; hypertension; tumor