280581-48-8Relevant articles and documents
Enantioselective Construction of Pyrimidine-Fused Diazepinone Derivatives Bearing a Tertiary Stereogenic Center Enabled by Iridium-Catalysed Intramolecular Allylic Substitution
Chan, Albert S. C.,Chan, Hoi Shan,Chen, Bin,He, Xiaobo,Jiang, Xiaoding,Liang, Hao,Pan, Bendu,Qian, Xu,Qiu, Liqin,Zhang, Yaqi
supporting information, p. 3227 - 3232 (2021/06/16)
The iridium-catalysed enantioselective intramolecular allylic substitution of pyrimidine-tethered allylic carbonates was developed. A wide range of chiral pyrimidine-fused diazepinone derivatives were successfully constructed in 88–96% yields with 85–99%
Discovery of Diaminopyrimidine Carboxamide HPK1 Inhibitors as Preclinical Immunotherapy Tool Compounds
Vara, Brandon A.,Levi, Samuel M.,Achab, Abdelghani,Candito, David A.,Fradera, Xavier,Lesburg, Charles A.,Kawamura, Shuhei,Lacey, Brian M.,Lim, Jongwon,Methot, Joey L.,Xu, Zangwei,Xu, Haiyan,Smith, Dustin M.,Piesvaux, Jennifer A.,Miller, J. Richard,Bittinger, Mark,Ranganath, Sheila H.,Bennett, David J.,Dimauro, Erin F.,Pasternak, Alexander
supporting information, p. 653 - 661 (2021/04/12)
Hematopoietic progenitor kinase 1 (HPK1), a serine/threonine kinase, is a negative immune regulator of T cell receptor (TCR) and B cell signaling that is primarily expressed in hematopoietic cells. Accordingly, it has been reported that HPK1 loss-of-function in HPK1 kinase-dead syngeneic mouse models shows enhanced T cell signaling and cytokine production as well as tumor growth inhibition in vivo, supporting its value as an immunotherapeutic target. Herein, we present the structurally enabled discovery of novel, potent, and selective diaminopyrimidine carboxamide HPK1 inhibitors. The key discovery of a carboxamide moiety was essential for enhanced enzyme inhibitory potency and kinome selectivity as well as sustained elevation of cellular IL-2 production across a titration range in human peripheral blood mononuclear cells. The elucidation of structure-activity relationships using various pendant amino ring systems allowed for the identification of several small molecule type-I inhibitors with promising in vitro profiles.
Synthesis and biological evaluation of pyrimidine derivatives as novel human Pin1 inhibitors
Cui, Guonan,Jin, Jing,Chen, Hualong,Cao, Ran,Chen, Xiaoguang,Xu, Bailing
supporting information, p. 2186 - 2197 (2018/03/28)
Pin1 (Protein interacting with NIMA1) is a cis–trans isomerase and promotes the amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of Pin1 might be a novel strategy for developing anticancer agents. Herein, a series of pyrimidi
HETEROCYCLIC UREA COMPOUNDS
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, (2013/07/05)
The present invention provides a compound of the following formula, racemates, enantiomers and salts thereof. Also provided is the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture
Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure-activity relationships of pyrimidine-5-carboxamide derivatives
Hisamichi, Hiroyuki,Naito, Ryo,Toyoshima, Akira,Kawano, Noriyuki,Ichikawa, Atsushi,Orita, Akiko,Orita, Masaya,Hamada, Noritaka,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
, p. 4936 - 4951 (2007/10/03)
Spleen tyrosine kinase (Syk) is a non-receptor-type tyrosine kinase which mediates diverse responses in haematopoietic cells. Therefore, Syk is an attractive therapeutic target, and in a study of Syk inhibitors as potentially new therapeutic agents, we di
