Computed Properties of C5H11ClN2O2SOn October 12, 2017 ,《Discovery of Novel Macrocyclic Hedgehog Pathway Inhibitors Acting by Suppressing the Gli-Mediated Transcription》 was published in Journal of Medicinal Chemistry. The article was written by Liu, Gang; Huang, Wenjing; Wang, Juan; Liu, Xiaohua; Yang, Jun; Zhang, Yu; Geng, Yong; Tan, Wenfu; Zhang, Ao. The article contains the following contents:
A systemic medicinal chem. campaign was conducted based on a literature hit compound I bearing the 4,5-dihydro-2H-benzo[b][1,5]oxazocin-6(3H)-one core through cyclization of two side substituents of the bicyclic skeleton combined with N-atom walking or ring walking and the central ring expansion or extraction approaches, leading to several series of structurally unique tricyclic compounds Among these, compound II was identified as the most potent against the Hedgehog (Hh) signaling pathway showing an IC50 value of 23 nM. Mechanism studies indicated that compound II inhibited the Hh signaling pathway by suppressing the expression of the transcriptional factors Gli rather than by interrupting the binding of Gli with DNA. We further observed that II was equally potent against both Smo wild type and the two major resistant mutants (Smo D473H and Smo W535L). It potently inhibited the proliferation of medulloblastoma cells and showed significant tumor growth inhibition in the ptch± ;p53-/- medulloblastoma allograft mice model. Though more studies are needed to clarify the precise interaction pattern of II with Gli, its promising in vitro and in vivo properties encourage further profiling as a new-generation Hh signaling inhibitor to treat tumors primarily or secondarily resistant to current Smo inhibitors. In the experimental materials used by the author, we found 4-Methyl-1-piperazinesulfonyl Chloride(cas: 1688-95-5Computed Properties of C5H11ClN2O2S)
4-Methyl-1-piperazinesulfonyl Chloride(cas: 1688-95-5) is a member of sulfamide. Sulfamide was used in the synthesis of: Schiff bases of the type ArCH=NSO2NH2; 1H,3H-2,1,3-benzothiadiazin-4-one-2,2-dioxide (BTDD); sulfamide analogs of oleoylethanolamide analogs in a study of PPARα activation.Computed Properties of C5H11ClN2O2S
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics