In 2016,Cheng, Hengmiao; Nair, Sajiv K.; Murray, Brion W.; Almaden, Chau; Bailey, Simon; Baxi, Sangita; Behenna, Doug; Cho-Schultz, Sujin; Dalvie, Deepak; Dinh, Dac M.; Edwards, Martin P.; Feng, Jun Li; Ferre, Rose Ann; Gajiwala, Ketan S.; Hemkens, Michelle D.; Jackson-Fisher, Amy; Jalaie, Mehran; Johnson, Ted O.; Kania, Robert S.; Kephart, Susan; Lafontaine, Jennifer; Lunney, Beth; Liu, Kevin K.-C.; Liu, Zhengyu; Matthews, Jean; Nagata, Asako; Niessen, Sherry; Ornelas, Martha A.; Orr, Suvi T. M.; Pairish, Mason; Planken, Simon; Ren, Shijian; Richter, Daniel; Ryan, Kevin; Sach, Neal; Shen, Hong; Smeal, Tod; Solowiej, Jim; Sutton, Scott; Tran, Khanh; Tseng, Elaine; Vernier, William; Walls, Marlena; Wang, Shuiwang; Weinrich, Scott L.; Xin, Shuibo; Xu, Haiwei; Yin, Min-Jean; Zientek, Michael; Zhou, Ru; Kath, John C. published 《Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants》.Journal of Medicinal Chemistry published the findings.HPLC of Formula: 90213-66-4 The information in the text is summarized as follows:
First generation EGFR TKIs (gefitinib, erlotinib) provide significant clin. benefit for NSCLC cancer patients with oncogenic EGFR mutations. Ultimately, these patients’ disease progresses, often driven by a second-site mutation in the EGFR kinase domain (T790M). Another liability of the first generation drugs is severe adverse events driven by inhibition of WT EGFR. As such, our goal was to develop a highly potent irreversible inhibitor with the largest selectivity ratio between the drug-resistant double mutants (L858R/T790M, Del/T790M) and WT EGFR. A unique approach to develop covalent inhibitors, optimization of reversible binding affinity, served as a cornerstone of this effort. PF-06459988 was discovered as a novel, third generation irreversible inhibitor, which demonstrates (i) high potency and specificity to the T790M-containing double mutant EGFRs, (ii) minimal intrinsic chem. reactivity of the electrophilic warhead, (iii) greatly reduced proteome reactivity relative to earlier irreversible EGFR inhibitors, and (iv) minimal activity against WT EGFR. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4HPLC of Formula: 90213-66-4)
2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. HPLC of Formula: 90213-66-4They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia