title: One-Pot Synthesis of Densely Substituted Pyrazolo[3,4-b]-4,7-dihydropyridines.
abstract: We have achieved a facile synthesis of a combinatorial library of densely substituted pyrazolo[3,4-b]-4,7-dihydropyridines- the mimics of antigenital wart drug podophyllotoxin-from 5-aminopyrazoles and 4-(methylthio) 4H-chromenes. The C(4) pyrazolyl 4H-chromenes, which also possess structural features of podophyllotoxin, were isolable intermediates in the two-step, one-pot condensation. The condensation took place in a one-pot, multicomponent manner when 3-oxo-3-phenylpropanenitriles, hydrazine (precursors for 5-aminopyrazoles) and 4-(methylthio)-4H-chromenes were heated in refluxing ethanol. The condensation, however, stops at 4H-chromene stage when methyl hydrazine or phenylhydrazine were employed. Our findings offer an opportunity for synthesis of a combinatorial library of podophyllotoxin mimics, thus paving the way for discovery of lead candidates for cancer treatment.
authors.affiliation: Department of Chemistry, Pondicherry University , Puducherry-605 014, India.|Center for Bioinformatics, Pondicherry University , Puducherry-605 014, India.
authors.forename: H Surya Prakash
authors.identifier: 0000-0003-0816-0116
authors.initials: HSP
authors.lastname: Rao
authors.affiliation: Department of Chemistry, Pondicherry University , Puducherry-605 014, India.|Center for Bioinformatics, Pondicherry University , Puducherry-605 014, India.
authors.forename: Lakshmi Narayana
authors.initials: LN
authors.lastname: Adigopula
authors.affiliation: Center for Bioinformatics, Pondicherry University , Puducherry-605 014, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Ramadas
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001578:Benzopyrans / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D004095:Dihydropyridines / Q000138:chemical synthesis*; D055808:Drug Discovery; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry; D011034:Podophyllotoxin / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis*; D054852:Small Molecule Libraries / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D004095:Dihydropyridines; D006834:Hydrazines; D009570:Nitriles; D011720:Pyrazoles; D054852:Small Molecule Libraries; C029424:hydrazine; C410426:3-oxo-3-phenylpropanenitrile; D011034:Podophyllotoxin
keywords: cancer treatment; combinatorial library; one-pot synthesis; podophyllotoxin mimics; pyrazolo[3,4-b]-4,7-dihydropyridines