214983-00-3Relevant academic research and scientific papers
Synthesis and tyrosine kinase inhibitory activity of a series of 2- amino-8H-pyrido[2,3-d]pyrimidines: Identification of potent, selective platelet-derived growth factor receptor tyrosine kinase inhibitors
Boschelli, Diane H.,Wu, Zhipei,Klutchko, Sylvester R.,Showalter, H. D. Hollis,Hamby, James M.,Lu, Gina H.,Major, Terry C.,Dahring, Tawny K.,Batley, Brian,Panek, Robert L.,Keiser, Joan,Hartl, Brian G.,Kraker, Alan J.,Klohs, Wayne D.,Roberts, Bill J.,Patmore, Sandra,Elliott, William L.,Steinkampf, Randy,Bradford, Laura A.,Hallak, Hussein,Doherty, Annette M.
, p. 4365 - 4377 (1998)
Screening of a compound library led to the identification of 2-amino-6- (2,6-dichlorophenyl)-8-methylpyrido[2,3-d]pyrimidine (1) as a inhibitor of the platelet-derived growth factor receptor (PDGFr), fibroblast growth factor receptor (FGFr), and c-src tyrosine kinases (TKs). Replacement of the primary amino group at C-2 of 1 with a 4-(N,N-diethylaminoethoxy)phenylamino group yielded 2a, which had greatly increased activity against all three TKs. In the present work, variation of the aromatic group at C-6 and of the alkyl group at N-8 of the pyrido[2,3d]pyrimidine core provided several analogues that retained potency, including derivatives that were biased toward inhibition of the TK activity of PDGFr. Analogues of 2a with a 3-thiophene or an unsubstituted phenyl group at C-6 were the most potent inhibitors. Compound 54, which had IC50 values of 31, 88, and 31 nM against PDGFr, FGFr, and c-src TK activity, respectively, was active in a variety of PDGF- dependent cellular assays and blocked the in vivo growth of three PDGF- dependent tumor lines.
Design of pyrido[2,3-d]pyrimidin-7-one inhibitors of receptor interacting protein kinase-2 (RIPK2) and nucleotide-binding oligomerization domain (NOD) cell signaling
Nikhar, Sameer,Siokas, Ioannis,Schlicher, Lisa,Lee, Seungheon,Gyrd-Hansen, Mads,Degterev, Alexei,Cuny, Gregory D.
, (2021/02/22)
Receptor interacting protein kinase-2 (RIPK2) is an enzyme involved in the transduction of pro-inflammatory nucleotide-binding oligomerization domain (NOD) cell signaling, a pathway implicated in numerous chronic inflammatory conditions. Herein, a pyrido[
PROTEIN KINASE INHIBITORS AND USES THEREOF FOR THE TREATMENT OF DISEASES AND CONDITIONS
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Paragraph 0106; 0119; 0120; 0121; 0122; 0125-0127, (2020/11/30)
Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2) and/or receptor interacting kinase 3 (RIPK3). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 or RIPK3 could provide therapeutic benefit. Compounds that function as RIPK3 inhibitors provide therapeutic benefit in the treatment of inflammatory and degenerative conditions.
PYRIDO[2,3-D]PYRIMIDIN-7ONES AND RELATED COMPOUNDS AS INHIBITORS OF PROTEIN KINASES
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Paragraph 0059-0060; 0065-0067; 0006; 0008, (2018/12/13)
Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds having the structures below (I) are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.
