Synthesis and β-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one.
10.1016/S1875-5364(13)60098-9
- Author:
Ren-Ren BAI
1
,
2
,
3
;
Sheng-Tao XU
1
,
4
;
Jie LIU
1
,
4
;
Wen HONG
5
;
Yi-Qun TANG
5
;
Xiao-Ming WU
1
,
4
;
Wei-Jia XIE
1
,
6
;
He-Quan YAO
1
,
4
;
Jin-Yi XU
1
,
7
Author Information
1. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
3. Jiangsu Honghui Medical Co., Ltd., Nanjing 210008, China.
4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
5. Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
6. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: henry1202x@hotmail.com.
7. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: jinyixu@china.com.
- Publication Type:Journal Article
- Keywords:
Antihypertensive activity;
Hybrids;
Isochroman-4-one derivatives;
Oxime ethers;
β-Adrenergic blocking activity
- MeSH:
Adrenergic beta-Antagonists;
chemical synthesis;
chemistry;
pharmacology;
Animals;
Antihypertensive Agents;
chemical synthesis;
chemistry;
pharmacology;
Benzopyrans;
chemical synthesis;
chemistry;
pharmacology;
Drugs, Chinese Herbal;
chemical synthesis;
chemistry;
pharmacology;
Humans;
Hypertension;
drug therapy;
physiopathology;
Male;
Molecular Structure;
Oximes;
chemistry;
Rats;
Rats, Sprague-Dawley;
Structure-Activity Relationship
- From:
Chinese Journal of Natural Medicines (English Ed.)
2013;11(5):538-545
- CountryChina
- Language:English
-
Abstract:
AIM:In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized.
METHOD:Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, β1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria.
RESULTS:Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited β1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%).
CONCLUSION:The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.
