title: Synthesis and biological evaluation of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties as positive inotropic agents.
abstract: Two series of [1,2,4]triazolo[3,4-a]phthalazine and tetrazolo[5,1-a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)tetrazolo[5,1-a]phthalazine. 8 m in particular was identified as the most potent with an increased stroke volume of 12.02 ± 0.20% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10(-5)  m. The chronotropic effects of the compounds that exhibited good potency were also evaluated.
authors.affiliation: Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Liang-Peng
authors.initials: LP
authors.lastname: Sun
authors.forename: Long-Xu
authors.initials: LX
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Che
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Song
authors.forename: Xun
authors.initials: X
authors.lastname: Cui
authors.forename: Hu-Ri
authors.initials: HR
authors.lastname: Piao
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006325:Heart Atria / Q000503:physiopathology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020105:Milrinone / Q000737:chemistry / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D020105:Milrinone