title: Synthesis of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: potent and selective adenosine A3 receptor antagonists.
abstract: A series of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 5 was prepared from 2-amino-3-cyano-4-trifluoromethyl-6-phenylpyridine 1 in two steps via formation of iminoether 3 followed by reaction with different aroylhydrazides 4. Representative products 5 were evaluated for their affinity towards all four subtypes of human adenosine receptors. Compounds 2-(3-fluorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5b), 2-(furan-2-yl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5d), and 2-(furan-2-yl)-5-methyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5j) showed high affinity for the A3 receptors, with Ki values of 8.1, 10.4, and 12.1 nM, respectively, and were >1000-fold selective versus all other adenosine receptor subtypes.
authors.affiliation: Fluoroorganic Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Andhra Pradesh, India.
authors.forename: Veeraswamy
authors.initials: V
authors.lastname: Banda
authors.forename: Balakumar
authors.initials: B
authors.lastname: Chandrasekaran
authors.forename: Meryem
authors.initials: M
authors.lastname: Köse
authors.forename: Christin
authors.initials: C
authors.lastname: Vielmuth
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Kurumurthy
authors.initials: K
authors.lastname: Chavva
authors.forename: Santhosh Kumar
authors.initials: SK
authors.lastname: Gautham
authors.forename: Sambasivarao
authors.initials: S
authors.lastname: Pillalamarri
authors.forename: Raghuprasad
authors.initials: R
authors.lastname: Mylavaram
authors.forename: Raghuramarao
authors.initials: R
authors.lastname: Akkinepally
authors.forename: Shanthanrao
authors.initials: S
authors.lastname: Pamulaparthy
authors.forename: Narsaiah
authors.initials: N
authors.lastname: Banda
mesh_terms: D058918:Adenosine A3 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043684:Receptor, Adenosine A3 / Q000187:drug effects* / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D011743:Pyrimidines; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1
keywords: 2-Aminonicotinonitrile; Adenosine receptors; Aroyl hydrazide; Orthoacetate; Orthoformate