title: C-C bond formation at C-2 of a quinoline ring: synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors.
abstract: A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl(3)-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC(50) ∼0.89 μM) is presented.
authors.affiliation: Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, India.
authors.forename: K Shiva
authors.initials: KS
authors.lastname: Kumar
authors.forename: S
authors.initials: S
authors.lastname: Kiran Kumar
authors.forename: B
authors.initials: B
authors.lastname: Yogi Sreenivas
authors.forename: Dhilli Rao
authors.initials: DR
authors.lastname: Gorja
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Kapavarapu
authors.forename: D
authors.initials: D
authors.lastname: Rambabu
authors.forename: G
authors.initials: G
authors.lastname: Rama Krishna
authors.forename: C Malla
authors.initials: CM
authors.lastname: Reddy
authors.forename: M V
authors.initials: MV
authors.lastname: Basaveswara Rao
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000737:chemistry; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry; D008968:Molecular Conformation; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D007211:Indoles; D058988:Phosphodiesterase 4 Inhibitors; D011804:Quinolines; D000077410:Aluminum Chloride; D002244:Carbon; C037219:quinoline; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C083774:2-chloroquinoline