title: Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones.
abstract: Several members of the quinazoline class of known tyrosine kinase inhibitors are approved anticancer agents, often showing selectivity for receptors of the HER/ErbB-family. Combining structural elements of this class with the bisindolylmethanone-structure led to a series of novel compounds. These compounds inhibited EGFR in the nanomolar range. Moreover, inhibition of EGFR autophosphorylation in intact A431 cells was shown, with IC(50) values ranging form 0.3-1μM for compound 42, and 0.1-0.3μM for 45. In a panel of 42 human tumor cell lines the sensitivity profile of the novel compounds was shown to be similar to that of the quinazoline class of tyrosine kinase inhibitors lapatinib and erlotinib (Tarceva®).
authors.affiliation: Department of Pharmaceutical Chemistry I, University of Regensburg, D-93040 Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Beckers
authors.forename: Andreas
authors.initials: A
authors.lastname: Sellmer
authors.forename: Emerich
authors.initials: E
authors.lastname: Eichhorn
authors.forename: Herwig
authors.initials: H
authors.lastname: Pongratz
authors.forename: Christoph
authors.initials: C
authors.lastname: Schächtele
authors.forename: Frank
authors.initials: F
authors.lastname: Totzke
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kelter
authors.forename: Rebekka
authors.initials: R
authors.lastname: Krumbach
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.forename: Frank-D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: Siavosh
authors.initials: S
authors.lastname: Mahboobi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C571599:(4-(3-chloro-4-fluorophenylamino)thieno(2,3-d)pyrimidin-6-yl)(5-hydroxy-1H-indol-2-yl)methanone; C571598:(4-(3-chlorophenylamino)thieno(2,3-d)pyrimidin-6-yl)(1H-indol-2-yl)methanone; D000970:Antineoplastic Agents; D007211:Indoles; D011743:Pyrimidines; D011799:Quinazolines; D066246:ErbB Receptors; C030986:pyrimidine