DiMauro, Erin F.; Newcomb, John; Nunes, Joseph J.; Bemis, Jean E.; Boucher, Christina; Chai, Lilly; Chaffee, Stuart C.; Deak, Holly L.; Epstein, Linda F.; Faust, Ted; Gallant, Paul; Gore, Anu; Gu, Yan; Henkle, Brad; Hsieh, Faye; Huang, Xin; Kim, Joseph L.; Lee, Josie H.; Martin, Matthew W.; McGowan, David C.; Metz, Daniela; Mohn, Deanna; Morgenstern, Kurt A.; Oliveira-dos-Santos, Antonio; Patel, Vinod F.; Powers, David; Rose, Paul E.; Schneider, Stephen; Tomlinson, Susan A.; Tudor, Yan-Yan; Turci, Susan M.; Welcher, Andrew A.; Zhao, Huilin; Zhu, Li; Zhu, Xiaotian published the artcile< Structure-Guided Design of Aminopyrimidine Amides as Potent, Selective Inhibitors of Lymphocyte Specific Kinase: Synthesis, Structure-Activity Relationships, and Inhibition of in Vivo T Cell Activation>, Product Details of C19H34O2, the main research area is aminopyrimidine amide preparation selective inhibitor lymphocyte specific kinase; T cell activation proliferation inhibitor aminopyrimidine amide; crystal structure lymphocyte specific kinase cocrystal aminopyrimidine amide; mol structure lymphocyte specific kinase cocrystal aminopyrimidine amide.
The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic evidence, including knockout mice and human mutations, demonstrates that Lck kinase activity is critical for normal T cell development, activation, and signaling. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. With the aid of x-ray structure-based anal., aminopyrimidine amides were designed from aminoquinazolines, which had previously been demonstrated to exhibit potent inhibition of Lck and T cell proliferation. The authors describe the synthesis and structure-activity relations of novel aminopyrimidine amides possessing improved cellular potency and selectivity profiles relative to their aminoquinazoline predecessors. Orally bioavailable compound 2-methyl-N-[2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-pyrimidinyl]-5-[[[3-(trifluoromethyl)phenyl]carbonyl]amino]benzamide inhibited the anti-CD3-induced production of interleukin-2 (IL-2) in mice in a dose-dependent manner (ED50 = 9.4 mg/kg). The crystal and mol. structures of cocrystals of Lck kinase with 4-methyl-N3-[2-[4-(4-methylpiperazin-1-yl)phenylamino]pyrimidin-5-yl]-N1-[3-(trifluoromethyl)phenyl]isophthalamide and 2-methyl-N-[4-methyl-3-[[[2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-5-pyrimidinyl]amino]carbonyl]phenyl]-3-(trifluoromethyl)benzamide were determined by x-ray crystallog.
Journal of Medicinal Chemistry published new progress about Amides Role: PAC (Pharmacological Activity), PKT (Pharmacokinetics), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.
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