title: Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors.
abstract: A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.
authors: Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India.
authors: Dhilli Rao
authors: DR
authors: Gorja
authors: Soumita
authors: S
authors: Mukherjee
authors: Chandana Lakshmi T
authors: CL
authors: Meda
authors: Girdhar Singh
authors: GS
authors: Deora
authors: K Lalith
authors: KL
authors: Kumar
authors: Ankit
authors: A
authors: Jain
authors: Girish H
authors: GH
authors: Chaudhari
authors: Keerthana S
authors: KS
authors: Chennubhotla
authors: Rakesh K
authors: RK
authors: Banote
authors: Pushkar
authors: P
authors: Kulkarni
authors: Kishore V L
authors: KV
authors: Parsa
authors: K
authors: K
authors: Mukkanti
authors: Manojit
authors: M
authors: Pal
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D000077152:Olanzapine; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D014150:Antipsychotic Agents; D058988:Phosphodiesterase 4 Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001569:Benzodiazepines; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human; D000077152:Olanzapine