879088-41-2Relevant articles and documents
Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement
Zhao, Fei,Wu, Yiran,Zhou, Fang,Xue, Dongxiang,Zhao, Simeng,Lu, Wanglong,Liu, Xiaoyan,Hu, Tao,Qiu, Yanli,Li, Rongyan,Gu, Tangjie,Xu, Yueming,Xu, Fei,Zhong, Guisheng,Jiang, Zhongxing,Zhao, Suwen,Tao, Houchao
supporting information, p. 13830 - 13840 (2021/09/28)
Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and th
Preparation method of vimodegil
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, (2020/05/05)
The invention provides a preparation method of vimodegil. 2-chloro-5-nitroacetophenone is used as a raw material; 5-oxo-5-(2-chloro-5-nitrophenyl) n-valeraldehyde is prepared through an addition reaction between 2-chloro-5-nitroacetophenone and acrolein,
Smooth receptor ligand
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Paragraph 0085; 0252; 0260; 0281, (2020/04/01)
The invention relates to the technical field of biology, particularly to a smooth receptor ligand, and provides a smooth receptor ligand or an isomer prodrug, a solvate and a pharmaceutically acceptable salt thereof, wherein the structural formula of the smooth receptor ligand is A-linker-B, A is an extracellular domain ligand structure, B is a transmembrane domain ligand structure, and Linker isa linear subunit inactive to the smooth receptor. According to the novel double-end small molecule ligand for the smooth receptor, by combining the crystal structure data of the smooth receptor, a linker is introduced into the proper sites of an extracellular domain ligand and a transmembrane domain ligand to obtain brand-new double-end ligand small molecules, so that the interaction between the ligand and the receptor and the biological activity of the ligand are enhanced.
Selective Late-Stage Oxygenation of Sulfides with Ground-State Oxygen by Uranyl Photocatalysis
Li, Yiming,Rizvi, S. Aal-e-Ali,Hu, Deqing,Sun, Danwen,Gao, Anhui,Zhou, Yubo,Li, Jia,Jiang, Xuefeng
, p. 13499 - 13506 (2019/08/21)
Oxygenation is a fundamental transformation in synthesis. Herein, we describe the selective late-stage oxygenation of sulfur-containing complex molecules with ground-state oxygen under ambient conditions. The high oxidation potential of the active uranyl cation (UO22+) enabled the efficient synthesis of sulfones. The ligand-to-metal charge transfer process (LMCT) from O 2p to U 5f within the O=U=O group, which generates a UV center and an oxygen radical, is assumed to be affected by the solvent and additives, and can be tuned to promote selective sulfoxidation. This tunable strategy enabled the batch synthesis of 32 pharmaceuticals and analogues by late-stage oxygenation in an atom- and step-efficient manner.
Divergent Late-Stage (Hetero)aryl C?H Amination by the Pyridinium Radical Cation
Ham, Won Seok,Hillenbrand, Julius,Jacq, Jér?me,Genicot, Christophe,Ritter, Tobias
supporting information, p. 532 - 536 (2019/01/04)
(Hetero)arylamines constitute some of the most prevalent functional molecules, especially as pharmaceuticals. However, structurally complex aromatics currently cannot be converted into arylamines, so instead, each product isomer must be assembled through a multistep synthesis from simpler building blocks. Herein, we describe a late-stage aryl C?H amination reaction for the synthesis of complex primary arylamines that other reactions cannot access directly. We show and rationalize through a mechanistic analysis the reasons for the wide substrate scope and the constitutional diversity of the reaction, which gives access to molecules that would not have been readily available otherwise.
A [...] synthesis of intermediates method and application
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, (2019/03/28)
The invention relates to a method for synthesizing intermediate [...] and application, which belongs to the field of organic synthesis, in particular to intermediate 2 - (2 - chloro - 5 - nitrophenyl) pyridine (i.e. compound A) preparation process, compri
Synthetic Path To Pharmaceutically Acceptable Vismodegib
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, (2018/10/19)
The present invention relates to a new route of synthesis to obtain pharmaceutically acceptable Vismodegib. In addition, besides the synthesis also suitable pharmaceutical compositions and the use of the compound for the treatment of basal-cell carcinomas
Method for preparing erivedge by adopting microchannel reaction device
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Paragraph 0039; 0040; 0041; 0047; 0052, (2018/06/21)
The invention discloses a method for preparing erivedge by adopting a microchannel reaction device. The method comprises the following steps: by using 2-phenylpyridine as a starting material, preparing an important intermediate 4-chloro-3-(pyridine-2-yl) aniline by metal catalysis amination, oxidation and reduction reaction in sequence, finally carrying out oxidation and amidation reaction with 2-chloro-1-methyl-4-(methylsulfonyl)benzene by two-step continuous flow in the novel microchannel reaction device, and preparing the erivedge. The microchannel reaction device has the characteristics ofcheap price, convenience in transportation and cleaning, higher heat and mass transfer efficiency and easier industrial amplification and the like. Compared with the prior art, the synthesis method has the advantages that the starting material is simple and cheap and is easy to obtain, the process is concise, the production cost can be effectively reduced, and the adaptability to industrial production is achieved.
Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings
Li, Wenlu,Sun, Qinsheng,Song, Lu,Gao, Chunmei,Liu, Feng,Chen, Yuzong,Jiang, Yuyang
, p. 721 - 733 (2017/11/01)
PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231.
Synthesis method of vismodegib
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, (2017/07/19)
The invention discloses a synthesis method of vismodegib. The method comprises the following reactions: firstly, enabling 2-chloro-5-nitrophenyl boronic acid and 2-bromopyridine to make a coupled reaction to generate an intermediate 2-(2-chloro-5-nitro) phenylpyridine; reducing nitro in the 2-(2-chloro-5-nitro) phenylpyridine to amino so as to obtain 2-(2-chloro-5-amino) phenylpyridine; finally, enabling the 2-(2-chloro-5-amino) phenylpyridine and 2-chloro-4-methyl sulfuryl benzaldehyde to make a catalytic reaction to generate the vismodegib. The synthesis method is low in price of raw materials, easy in raw material obtaining, simple and convenient to operate and less in consumption of a catalyst; the reaction product is high in yield, reaction conditions are mild, and aftertreatment is simple in technology and mainly adopts column separation, so that industrial mass production can be realized.
