Computed Properties of C4H2Cl2N2In 2020 ,《Optimization of a series of potent, selective and orally bioavailable SYK inhibitors》 was published in Bioorganic & Medicinal Chemistry Letters. The article was written by Grimster, Neil P.; Gingipalli, Lakshmaiah; Barlaam, Bernard; Su, Qibin; Zheng, XiaoLan; Watson, David; Wang, Haixia; Simpson, Iain; Pike, Andy; Balazs, Amber; Boiko, Scott; Ikeda, Timothy P.; Impastato, Anna C.; Jones, Natalie H.; Kawatkar, Sameer; Kemmitt, Paul; Lamont, Scott; Patel, Joe; Read, Jon; Sarkar, Ujjal; Sha, Li; Tomlinson, Ronald C.; Wang, Haiyun; Wilson, David M.; Zehnder, Troy E.; Wang, Lianghe; Wang, Peng; Goldberg, Frederick W.; Shao, Wenlin; Fawell, Stephen; Dry, Hannah; Dowling, James E.; Edmondson, Scott D.. The article contains the following contents:
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 chem. probe, 17, which exhibits excellent potency at SYK, and an adequate rodent PK profile to support in vivo efficacy/PD studies. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Computed Properties of C4H2Cl2N2)
2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Computed Properties of C4H2Cl2N2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia