title: Molecular design and synthesis of 1,4-disubstituted piperazines as α(1)-adrenergic receptor blockers.
abstract: A new series of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide and 3,5,6,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-one derivatives were designed, synthesized, their binding and functional properties as α1-adrenoreceptors blockers were evaluated. A new validated α1-adrenoreceptor blocker pharmacophore model (hypothesis) was generated using Discovery Studio 2.5. The compare-fit study for the designed molecules with the generated hypothesis was fulfilled and several compounds showed significant high fit values. Compounds IVa-c, VIIa-d, VIIIa-c, Xa-c, XIa-d have shown blocking activity ranging from 46.73% up to 94.74% compared to 99.17% for prazosin.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbasia 11566, Cairo, Egypt. Electronic address: dalal999@hotmail.com.
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Abou El-Ella
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El Aini 11562, Cairo, Egypt.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Hussein
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbasia 11566, Cairo, Egypt.
authors.forename: Rabah A T
authors.initials: RA
authors.lastname: Serya
authors.affiliation: Department of Pharmaceutical Chemistry, Misr University for Science and Technology, Al-Motamayez, 6Th October, Egypt.
authors.forename: Rana M
authors.initials: RM
authors.lastname: Abdel Naby
authors.affiliation: Department of Pharmacology, Medical Division, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Al-Abd
authors.affiliation: Department of Pharmacology, Medical Division, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Dalia O
authors.initials: DO
authors.lastname: Saleh
authors.affiliation: Department of Pharmacology, Medical Division, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Wafaa I
authors.initials: WI
authors.lastname: El-Eraky
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbasia 11566, Cairo, Egypt. Electronic address: abouzid@yahoo.com.
authors.forename: Khaled A M
authors.initials: KA
authors.lastname: Abouzid
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1
keywords: Phenylpiperazines; Pyridothienopyrimidine; α(1)-Adrenoreceptors blockers