title: Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors.
abstract: A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-α release assay.
authors.affiliation: Department of Chemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea; Oscotec Inc., 694-1 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.
authors.forename: Jang-Sik
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Oscotec Inc., 694-1 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.
authors.forename: Hae-Jun
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Oscotec Inc., 694-1 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.
authors.forename: Se-Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea.
authors.forename: Byung Il
authors.initials: BI
authors.lastname: Lee
authors.affiliation: Genosco, 767C Concord Avenue, 2nd Floor, Cambridge, MA 02138, USA.
authors.forename: Jaekyoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Genosco, 767C Concord Avenue, 2nd Floor, Cambridge, MA 02138, USA.
authors.forename: Ho-Juhn
authors.initials: HJ
authors.lastname: Song
authors.affiliation: Genosco, 767C Concord Avenue, 2nd Floor, Cambridge, MA 02138, USA.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Koh
authors.affiliation: Oscotec Inc., 694-1 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea. Electronic address: jhkim@oscotec.com.
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: phlee@kangwon.ac.kr.
authors.forename: Phil Ho
authors.initials: PH
authors.lastname: Lee
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C000606692:pyrazolylpyrimidine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606898:Syk protein, rat
keywords: Pyrazolylpyrimidine; Rheumatoid arthritis; Spleen tyrosine kinase; Structure–activity relationship; Syk inhibitors