37968-69-7Relevant academic research and scientific papers
Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5- b]pyridazines for the Treatment of Human African Trypanosomiasis
Tear, Westley F.,Bag, Seema,Diaz-Gonzalez, Rosario,Ceballos-Pérez, Gloria,Rojas-Barros, Domingo I.,Cordon-Obras, Carlos,Pérez-Moreno, Guiomar,García-Hernández, Raquel,Martinez-Martinez, Maria Santos,Ruiz-Perez, Luis Miguel,Gamarro, Francisco,Gonzalez Pacanowska, Dolores,Caffrey, Conor R.,Ferrins, Lori,Manzano, Pilar,Navarro, Miguel,Pollastri, Michael P.
, p. 756 - 783 (2020/02/04)
From a high-throughput screen of 42 44 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against h
Optimization of a series of potent, selective and orally bioavailable SYK inhibitors
Balazs, Amber,Barlaam, Bernard,Boiko, Scott,Dowling, James E.,Dry, Hannah,Edmondson, Scott D.,Fawell, Stephen,Gingipalli, Lakshmaiah,Goldberg, Frederick W.,Grimster, Neil P.,Ikeda, Timothy P.,Impastato, Anna C.,Jones, Natalie H.,Kawatkar, Sameer,Kemmitt, Paul,Lamont, Scott,Patel, Joe,Pike, Andy,Read, Jon,Sarkar, Ujjal,Sha, Li,Shao, Wenlin,Simpson, Iain,Su, Qibin,Tomlinson, Ronald C.,Wang, Haixia,Wang, Haiyun,Wang, Lianghe,Wang, Peng,Watson, David,Wilson, David M.,Zehnder, Troy E.,Zheng, XiaoLan
supporting information, (2020/08/21)
Spleen tyrosine kinase (SYK) is a non-receptor cytosolic kinase. Due to its pivotal role in B cell receptor and Fc-receptor signaling, inhibition of SYK has been targeted in a variety of disease areas. Herein, we report the optimization of a series of potent and selective SYK inhibitors, focusing on improving metabolic stability, pharmacokinetics and hERG inhibition. As a result, we identified 30, which exhibited no hERG activity but unfortunately was poorly absorbed in rats and mice. We also identified a SYK chemical probe, 17, which exhibits excellent potency at SYK, and an adequate rodent PK profile to support in vivo efficacy/PD studies.
One-pot synthesis of meridianins and meridianin analogues via indolization of nitrosoarenes
Tibiletti, Francesco,Simonetti, Marco,Nicholas, Kenneth M.,Palmisano, Giovanni,Parravicini, Matteo,Imbesi, Federico,Tollari, Stefano,Penoni, Andrea
experimental part, p. 1280 - 1288 (2010/04/02)
Meridianins, marine alkaloids known as kinase inhibitors with an indole skeleton, and meridianin analogues were produced regioselectively and in moderate to good yields by thermal annulation of nitrosoarenes with 2-amino-4-ethynylpyrimidine and 2-chloro-4-ethynylpyrimidine, respectively, through a novel and atom-economical indolization process.
Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors
Alam, Mahbub,Beevers, Rebekah E.,Ceska, Tom,Davenport, Richard J.,Dickson, Karen M.,Fortunato, Mara,Gowers, Lewis,Haughan, Alan F.,James, Lynwen A.,Jones, Mark W.,Kinsella, Natasha,Lowe, Christopher,Meissner, Johannes W.G.,Nicolas, Anne-Lise,Perry, Benjamin G.,Phillips, David J.,Pitt, William R.,Platt, Adam,Ratcliffe, Andrew J.,Sharpe, Andrew,Tait, Laura J.
, p. 3463 - 3467 (2008/02/09)
The development of a series of novel aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay are discussed.
