Targeting dihydrofolate reductase: Design, synthesis and biological evaluation of novel 6-substituted pyrrolo[2,3-d]pyrimidines as nonclassical antifolates and as potential antitumor agents was written by Gao, Tianfeng;Zhang, Congying;Shi, Xiaowei;Guo, Ran;Zhang, Kai;Gu, Jianmin;Li, Lin;Li, Shuolei;Zheng, Qianqian;Cui, Mengyu;Cui, Miao;Gao, Xingmei;Liu, Yi;Wang, Lei. And the article was included in European Journal of Medicinal Chemistry in 2019.Related Products of 638-07-3 The following contents are mentioned in the article:
A novel series of 6-substituted pyrrolo[2,3-d]pyrimidines with reversed amide moieties from the lead compound I (R = 4-pyridyl) were designed and synthesized as nonclassical antifolates and as potential antitumor agents. Target compounds II were successfully obtained through two sequential condensation reactions from the key intermediate 2-amino-6-(2-aminoethyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one. In preliminary antiproliferation assay, all compounds demonstrated submicromolar to nanomolar inhibitory effects against KB tumor cells, whereas compounds I (R = 2-, 3-, 4-pyridyl) also exhibited nanomolar antiproliferative activities toward SW620 and A549 cells. In particular, compounds I (R = 2-, 3-, 4-pyridyl) were significantly more potent than the pos. control methotrexate (MTX) and pemetrexed (PMX) to A549 cells. The growth inhibition induced cell cycle arrest at G1-phase with S-phase suppression. Along with the results of nucleoside protection assays, inhibition assays of dihydrofolate reductase (DHFR) clearly elucidated that the intracellular target of the designed compounds was DHFR. Mol. modeling studies suggested two binding modes of the target compounds with DHFR. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Related Products of 638-07-3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Related Products of 638-07-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics