title: Discovery of substituted 6-pheny-3H-pyridazin-3-one derivatives as novel c-Met kinase inhibitors.
abstract: We report a series of phenyl substituted pyridazin-3-ones substituted with morpholino-pyrimidines. The SAR of the phenyl was explored and their c-Met kinase and cell-based inhibitory activity toward c-Met driven cell lines were evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent morpholino-pyridazinone scaffold, with particular focus on the phenyl and pyrimidine substituents.
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seung-Tae
authors.initials: ST
authors.lastname: Kang
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-550, Republic of Korea.
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Achary
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-550, Republic of Korea.
authors.forename: Heejung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-550, Republic of Korea.
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Park
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-550, Republic of Korea.
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Yun
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-550, Republic of Korea.
authors.forename: Jong Yeon
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
authors.forename: Sang Un
authors.initials: SU
authors.lastname: Choi
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
authors.forename: Chonghak
authors.initials: C
authors.lastname: Chae
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
authors.forename: Chong Ock
authors.initials: CO
authors.lastname: Lee
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea. Electronic address: jdha@krict.re.kr.
authors.forename: Jae Du
authors.initials: JD
authors.lastname: Ha
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Ryu
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-550, Republic of Korea. Electronic address: sycho@krict.re.kr.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Cho
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D019859:Proto-Oncogene Proteins c-met
keywords: Cancer; Pyridazin-3-one; c-Met inhibitor