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Volumn 17, Issue 22, 2007, Pages 6373-6377

Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors

Author keywords

Alkynyl substituted 4 anilinoquinazoline; EGFR kinase inhibitor

Indexed keywords

6 HYDROXYPROPYNYL 4 ANILINOQUINAZOLINE; ALKYNYL GROUP; ANILINE DERIVATIVE; BROMINE DERIVATIVE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEFITINIB; LAPATINIB; QUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG;

EID: 35248837368     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.08.061     Document Type: Article
Times cited : (40)

References (25)
  • 17
    • 35248820467 scopus 로고    scopus 로고
    • note
    • The EGFR was purchased from Upstate (Active EGFR, Cat. No. 14-531) and used directly without further purification. Kinase assay experiments were performed according to the procedure as described in the booklet.
  • 22
    • 35248869097 scopus 로고    scopus 로고
    • note
    • +.
  • 23
    • 35248839887 scopus 로고    scopus 로고
    • note
    • 33P] MgAc/ATP cocktail containing magnesium acetate (50 mM) and ATP (500 μM). The reaction mixture of a total volume of 25 μl was incubated at 30 °C for 30 min. Five microliters of phosphoric acid (3%) was added to stop the reaction. An aliquot of 20 μl from reaction was transferred onto the center of a 2 cm × 2 cm P81 paper and allow the radiolabeled substrate to bind to the filter paper for 30 s. Wash the assay squares five times for 5 min with water. Transfer the assay squares to vial and add 5 ml scintillation cocktail. Read in scintillation counter by Beckman LS-6500 counter.
  • 24
    • 35248836350 scopus 로고    scopus 로고
    • Docking modeling was applied to assist SAR study. Briefly, the 3D structure of EGFR (pdb coded 2ito) was obtained from RCSB Protein Data Bank (http://www.rcsb.org/pdb/home/home.do). The structures of three compounds (Tarceva, 5e, and 6b) were generated and the energies were optimized on Meastro by using Ligpre (Schrödinger, USA). Molecular docking was conducted by using Glide with XP mode (detailed in user manual of Schrödinger), which allows flexible conformational search of the compounds against the target. For each inhibitor, five best docking modes were generated and its final interacting complex with EGFR was selected based on computed docking score of Glide.
  • 25
    • 35248835888 scopus 로고    scopus 로고
    • Glide docking scores of Iressa (-9.44), Tarceva (-10.83) as well as some active compounds such as 5e (-10.87), 6b (-9.88), and 6d (-3.42) showed that compound 5e is slightly favored over Iressa and Tarceva in EGFR kinase SAR.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.