title: Indenopyrazole oxime ethers: synthesis and β1-adrenergic blocking activity.
abstract: This paper reports the synthesis and cardiac activity of new β-blockers derived from (Z/E)-indeno[1,2-c]pyrazol-4(1H)-one oximes (5a,b). The latter compounds were allowed to react with epichlorohydrin, followed by reacting the oxiranyl derivatives formed (6a,b) with some aliphatic amines to give the target compounds (Z/E)-1-phenyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3-(substituted amino)propyl)oxime (7a-c) and (Z/E)-1-methyl-1H-indeno[1,2-c]pyrazol-4-one O-((2-hydroxy-3-(substituted amino)propyl)oxime (8a-c). These final products 7a-c and 8a-c were evaluated for their ability to modulate the cardiac performance of a prototype mammalian heart. The results showed that, out of these molecules tested, 7b elicits a more potent depressant effect on contractility and relaxation, and competitively antagonizes β1-adrenergic receptors.
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy; Department of Computer Engineering, Modeling, Electronics and Systems, University of Calabria, 87036 Rende CS, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258 - FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rochais
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Caputo
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy. Electronic address: maria_carmela.cerra@unical.it.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Cerra
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258 - FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen cedex, France. Electronic address: patrick.dallemagne@unicaen.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Filice
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258 - FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Genest
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pasqua
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puoci
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano SA, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy. Electronic address: s.sinicropi@unical.it.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
authors.affiliation: Chemistry Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Kashef
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C000602795:1-phenyl-1H-indeno(1,2-c)pyrazol-4-one O-((3-n-butylamino)-2-hydroxypropyl)oxime; D058671:Adrenergic beta-1 Receptor Antagonists; D004952:Esters; D010091:Oximes; D011720:Pyrazoles; D018342:Receptors, Adrenergic, beta-1
keywords: Hydroxypropanolamines; Indenopyrazole oximes; Indenopyrazoles; β-Adrenergic blocking agents; β-adrenoceptors