title: A new cascade reaction: concurrent construction of six and five membered rings leading to novel fused quinazolinones.
abstract: A one-pot cascade reaction has been developed leading to the concurrent construction of six and five membered fused N-heterocyclic rings of indazolo[3,2-b]quinazolinones. The methodology involved the reaction of isatoic anhydride, a hydrazine and o-iodo benzaldehyde in the presence of Pd(PPh(3))(4) and BINAP in MeCN. The mechanism of this cascade reaction is discussed. A variety of indazolo[3,2-b]quinazolinone derivatives were prepared by using this methodology in good yields, some of which were tested for their PDE4 inhibitory properties in vitro. The dose response and docking study performed using a representative compound is presented.
authors.affiliation: Custom Pharmaceutical Services, Dr Reddy's Laboratories Limited, Bollaram Road Miyapur, Hyderabad, 500 049, India.
authors.forename: K Siva
authors.initials: KS
authors.lastname: Kumar
authors.forename: P Mahesh
authors.initials: PM
authors.lastname: Kumar
authors.forename: V Sreenivasa
authors.initials: VS
authors.lastname: Rao
authors.forename: Ahamed A
authors.initials: AA
authors.lastname: Jafar
authors.forename: Chandana Lakshmi T
authors.initials: CL
authors.lastname: Meda
authors.forename: R
authors.initials: R
authors.lastname: Kapavarapu
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001547:Benzaldehydes / Q000737:chemistry; D002384:Catalysis; D002460:Cell Line; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry; D010078:Oxazines / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D000893:Anti-Inflammatory Agents; C406943:BINAP, 2-naphthol; D001547:Benzaldehydes; D006834:Hydrazines; D009281:Naphthalenes; D010078:Oxazines; D058988:Phosphodiesterase 4 Inhibitors; D052999:Quinazolinones; C029424:hydrazine; D010165:Palladium; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C037902:isatoic anhydride