title: Synthesis and β-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one.
abstract: OBJECTIVE
  In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized.
  
  
  METHODS
  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%).
  
  
  CONCLUSIONS
  The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Honghui Medical Co., Ltd., Nanjing 210008, China.
authors.forename: Ren-Ren
authors.initials: RR
authors.lastname: Bai
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Xu
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hong
authors.affiliation: Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Tang
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: henry1202x@hotmail.com.
authors.forename: Wei-Jia
authors.initials: WJ
authors.lastname: Xie
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: He-Quan
authors.initials: HQ
authors.lastname: Yao
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: jinyixu@china.com.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Xu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: C000591230:7,8-dihydroxy-3-methylisochroman-4-one; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004365:Drugs, Chinese Herbal; D010091:Oximes
keywords: Antihypertensive activity; Hybrids; Isochroman-4-one derivatives; Oxime ethers; β-Adrenergic blocking activity