A series of novel hybrids of natural isochroman-4-one bearing isopropanolamine moiety were designed, synthesized and evaluated for their antihypertensive activity. It was found that compound IIId, prepared by hybridizing N-isopropyl substituted isopropanolamine functionality to a phenolic oxygen of isochroman-4-one, exhibited potent β1-adrenoceptor blocking effect comparable to the well-known antihypertensive drug propranolol. Additionally, IIId significantly reduced the systolic and diastolic blood pressure in SHRs by over 40%, which was obviously stronger than the lead compounds 7,8-dihydroxy-3-methyl-isochroman-4-one (XJP) and its analogue XJP-B. Overall, IIId may be a promising antihypertensive candidate for further investigation.
|Number of pages||8|
|Journal||Bioorganic and Medicinal Chemistry|
|State||Published - May 1 2013|
Bibliographical noteFunding Information:
This study was financially supported by a grant from ‘Eleventh Five-Year’ Major Innovation Projects for New Drug Candidates (No. 2009ZX09103-128 ), Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province ( CXZZ11-0798 ), Fundamental Research Funds for the Central Universities ( JKY2011027 ) and Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University ( JKGQ201115 ).
Copyright 2013 Elsevier B.V., All rights reserved.
- Antihypertensive activity
- β-Adrenoceptor blockers
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry