Optimization of bipyridinyl pyrazole scaffolds via design, synthesis and screening of a new series of ROS1 kinase-modulating compounds

Mohammad M. Al-Sanea, K. Byung Sun Park, K. Ahmed Z. Abdelazem, Khalid B. Selim, Kyung Ho Yoo, Taebo Sim, Jin Sung Tae, So Ha Lee

Research output: Contribution to journalArticle


A series of rationally designed ROS1 tyrosine kinase inhibitors 6a-9b with bipyridinyl pyrazole scaffold was synthesized and screened. The scaffold itself has showed an exclusive selectivity profile over ROS1 closely related kinases,ALKand c-Met. The aim of this study was to further explore the structure-activity relationships (SAR) of the bipyridinyl pyrazole core structure, and to improve its ROS1 inhibitory potency. The rational of this study was to explore the nature of the proposed binding site for the pyrazoleNHsubstituents. Careful selections of pyrazoleNHsubstituent groups along with their regioisomers were considered. The compounds exhibited high degree of potency, IC50 values of 21-159 nM. A detailed SAR of bipyridinyl pyrazole scaffold has been finally well established and the virtual screening strategy, through molecular docking, has been performed for this type of ROS1 kinase inhibitors and the docked poses along with the activity data have gone in consistent with SAR specifications.

Original languageEnglish
Pages (from-to)305-311
Number of pages7
JournalBulletin of the Korean Chemical Society
Issue number1
Publication statusPublished - 2015 Jan 20


All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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