Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors

Bioorganic and Medicinal Chemistry

Volumn 22, Issue 15, 2014, Pages 3871-3878

  Park, Byung Sun ^a   Al Sanea, Mohammad M ^b,c   Abdelazem, Ahmed Z ^b,c   Park, Hye Mi ^b   Roh, Eun Joo ^b   Park, Hyun Mee ^b   Yoo, Kyung Ho ^b   Sim, Taebo ^b   Tae, Jin Sung ^a   Lee, So Ha ^b  

^a Yonsei University   (South Korea)

^b Korea Institute of Science and Technology   (South Korea)

^c University of Science and Technology (UST)   (South Korea)

Author keywords

Cancer; Kinase inhibitor; NSCLC; ROS1; Structure activity relationship; Suzuki coupling

Indexed keywords

1 [2 CHLORO 6 [3 (3 METHOXY 5 METHYLPHENYL) 1H PYRAZOL 4 YL]PYRIMIDIN 4 YL]AZETIDIN 3 OL; 1 [6 [3 (3 HYDROXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AZETIDIN 3 OL; 1 [6 [3 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AZETIDIN 3 OL; 1 [6 [5 (3 HYDROXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AZETIDIN 3 OL; 1 [6 [5 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AZETIDIN 3 OL; 1 [[6 [3 (3 HYDROXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO]PROPAN 2 OL; 1 [[6 [3 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO] PROPAN 2 OL; 1 [[6 [5 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO]PROPAN 1 OL; 2 (2 CHLORO 6 MORPHOLINOPYRIMIDIN 4 YL) 1 (3 METHOXY 5 METHYLPHENYL)ETHANONE; 2 (2,6 DICHLOROPYRIMIDIN 4YL) 1 (3 METHOXY 5 METHYLPHENYL)ETHANONE; 2 [2 CHLORO 6 (3 HYDROXYAZETIDIN 1 YL)PYRIMIDIN 4 YL] 1 (3 METHOXY 5 METHYLPHENYL)ETHANONE; 2 [2 CHLORO 6 [(2 HYDROXYPROPYL)AMINO]PYRIMIDIN 4 YL] 1 (3 METHOXY 5 METHYLPHENYL)ETHANONE; 3 METHYL 5 [1 METHYL 4 [6 MORPHOLINO 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL] 1H PYRAZOL 3 YL]PHENOL; 3 METHYL 5 [1 METHYL 4 [6 MORPHOLINO 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL] 1H PYRAZOL 5 YL]PHENOL; 3 [4 [6 [(4 HYDROXYBUTYL)AMINO] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL] 1 METHYL 1H PYRAZOL 3 YL] 5 METHYLPHENOL; 4 [2 CHLORO 6 [3 (3 METHOXY 5 METHYLPHENYL) 1H PYRAZOL 4 YL]PYRIMIDIN 4 YL]MORPHOLINE; 4 [6 [3 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]BUTAN 1 OL; 4 [6 [3 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]MORPHOLINE; 4 [6 [5 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]MORPHOLINE; 4 [[2 CHLORO 6 [3 (3 METHOXY 5 METHYLPHENYL) 1H PYRAZOL 4 YL]PYRIMIDIN 4 YL]AMINO]BUTAN 1 OL; 4 [[6 [5 (3 METHOXY 5 METHYLPHENYL) 1 METHYL 1H PYRAZOL 4 YL] 2 (PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO]BUTAN 1 OL; CRIZOTINIB; DASATINIB; IMATINIB; PROTEIN C ROS; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; PYRAZOLE DERIVATIVE; STAUROSPORINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ADENOSINE TRIPHOSPHATE; ONCOPROTEIN; PROTEIN BINDING; PROTEIN KINASE INHIBITOR; PYRAZOLE; PYRIDINE DERIVATIVE; ROS1 PROTEIN, HUMAN;

ARTICLE; BINDING SITE; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ASSAY; HUMAN; IC 50; MOLECULAR MODEL; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; ANTAGONISTS AND INHIBITORS; CHEMISTRY; METABOLISM; MOLECULAR DOCKING; PROTEIN TERTIARY STRUCTURE; SYNTHESIS;

ADENOSINE TRIPHOSPHATE; BINDING SITES; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS; PYRAZOLES; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84905117717     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.06.020     Document Type: Article

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