38694-47-2Relevant articles and documents
Design and Synthesis of Novel Macrocyclic Mer Tyrosine Kinase Inhibitors
Wang, Xiaodong,Liu, Jing,Zhang, Weihe,Stashko, Michael A.,Nichols, James,Miley, Michael J.,Norris-Drouin, Jacqueline,Chen, Zhilong,Machius, Mischa,DeRyckere, Deborah,Wood, Edgar,Graham, Douglas K.,Earp, H. Shelton,Kireev, Dmitri,Frye, Stephen V.
, p. 1044 - 1049 (2016)
Mer tyrosine kinase (MerTK) is aberrantly elevated in various tumor cells and has a normal anti-inflammatory role in the innate immune system. Inhibition of MerTK may provide dual effects against these MerTK-expressing tumors through reducing cancer cell survival and redirecting the innate immune response. Recently, we have designed novel and potent macrocyclic pyrrolopyrimidines as MerTK inhibitors using a structure-based approach. The most active macrocycles had an EC50 below 40 nM in a cell-based MerTK phosphor-protein ELISA assay. The X-ray structure of macrocyclic analogue 3 complexed with MerTK was also resolved and demonstrated macrocycles binding in the ATP binding pocket of the MerTK protein as anticipated. In addition, the lead compound 16 (UNC3133) had a 1.6 h half-life and 16% oral bioavailability in a mouse PK study.
Porphyrin-based design of bioinspired multitarget quadruplex ligands
Laguerre, Aurélien,Desbois, Nicolas,Stefan, Loic,Richard, Philippe,Gros, Claude P.,Monchaud, David
, p. 2035 - 2039 (2014)
Secondary nucleic acid structures, such as DNA and RNA quadruplexes, are potential targets for cancer therapies. Ligands that interact with these targets could thus find application as anticancer agents. Synthetic G-quartets have recently found numerous applications, including use as bioinspired G-quadruplex ligands. Herein, the design, synthesis and preliminary biophysical evaluation of a new prototype multitarget G-quadruplex ligand, PNAPorphySQ, are reported, where peptidic nucleic acid guanine (PNAG) was incorporated in the porphyrin-templated synthetic G-quartet (PorphySQ). Using fluorescence resonance energy transfer (FRET)-melting experiments, PorphySQ was shown to possess enhanced quadruplex-interacting properties thanks to the presence of four positively charged PNAG residues that improve its electrostatic interactions with the binding site of both DNA and RNA quadruplexes (i.e., their negatively charged and accessible G-quartets), thereby making PNAPorphySQ an interesting prototype of a multitarget ligand. Both the chemical stability and water solubility of PNAPorphySQ are improved over the non-PNA derivative (PorphySQ), which are desirable properties for drug development, and while improvements remain to be made, this ligand is a promising lead for the further development of multitarget G-quadruplex ligands.
A synthesis of (±)-stemoamide using the intramolecular propargylic Barbier reaction
Bates, Roderick W.,Sridhar
, p. 1979 - 1981 (2009)
A diastereoselective synthesis of the alkaloid stemoamide has been achieved using the intramolecular propargylic Barbier reaction to construct the seven-membered ring. Georg Thieme Verlag Stuttgart.
Intramolecular [4+1] pyrroline annulation approach to pyrrolizidine alkaloids. Formal total synthesis of (±)-supinidine
Hudlicky,Frazier,Kwart
, p. 3523 - 3526 (1985)
Dienic azide was found to yield two dehydropyrrolizidines on thermolysis. The synthesis of these compounds is described and the mechanistic implications as well as synthetic utility of this new annulation sequence is discussed.
Evidence That Trimethyllysine Hydroxylase Catalyzes the Formation of (2S,3S)-3-Hydroxy-Nε-trimethyllysine
Reddy, Y. Vijayendar,Al Temimi, Abbas H. K.,White, Paul B.,Mecinovi?, Jasmin
, p. 400 - 403 (2017)
Trimethyllysine hydroxylase (TMLH) is an Fe(II) and 2-oxoglutarate (2OG) dependent oxygenase involved in the biomedically important carnitine biosynthesis pathway. A combination of synthetic and NMR studies provides direct evidence that human TMLH catalyzes the stereoselective conversion of (2S)-Nε-trimethyllysine to (2S,3S)-3-hydroxy-Nε-trimethyllysine.
2-(1-bromocyclobutyl) pyridine and synthesis method thereof
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Paragraph 0008; 0029; 0040-0041; 0048; 0059-0060; 0067, (2020/11/23)
The invention belongs to the technical field of organic synthesis, and relates to 2- (1-bromocyclobutyl) pyridine and a synthesis method thereof. The 2 -(-1bromocyclobutyl) pyridine can be used as a medical intermediate, and the synthetic method of the compound comprises the following steps: by taking tetrahydropyrane- 2-ketone as a raw material, carrying out nine steps of reactions including substitution, ring closing, hydrolysis, substitution, substitution, reduction, grignard, substitution and substitution to prepare the 2- (-1bromocyclobutyl) pyridine, so that the synthetic route is simple, the cost is low, and the efficiency is high.
Palladium/Copper-catalyzed Oxidation of Aliphatic Terminal Alkenes to Aldehydes Assisted by p-Benzoquinone
Komori, Saki,Yamaguchi, Yoshiko,Murakami, Yuka,Kataoka, Yasutaka,Ura, Yasuyuki
, p. 3946 - 3955 (2020/07/06)
The development of an anti-Markovnikov Wacker-type oxidation for simple aliphatic alkenes is a significant challenge. Herein, a variety of aldehydes can be selectively obtained from various unbiased aliphatic terminal alkenes using PdCl2(MeCN)2/CuCl in the presence of p-benzoquinone (BQ) under mild reaction conditions. Isomerization of the terminal alkene to the internal alkene was suppressed via slow addition of the starting material to the reaction mixture. In addition to the Pd catalyst, CuCl and BQ were essential in order to obtain the anti-Markovnikov product with high selectivity. Terminal alkenes bearing a halogen substituent afforded their corresponding aldehydes with high anti-Markovnikov selectivity. The halogen acts as a directing group in the reaction. DFT calculations indicate that a μ-chloro Pd(II)?Cu(I) bimetallic species with BQ coordinated to Cu is the catalytically active species in the case of a terminal alkene without a directing group.
Synthesis method of 5-fluoro-2-(1-bromocyclopropyl) pyridine
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Paragraph 0005; 0016; 0022; 0027; 0033; 0038; 0044, (2019/08/01)
The invention relates to a synthesis method of 5-fluoro-2-(1-bromocyclopropyl) pyridine. 1,4-butyrolactone, ethyl 4-bromobutyrate and 5-fluoro-2-mercaptopyridine are used as raw materials to prepare 5-fluoro-2-(1-bromocyclopropyl) pyridine through eleven steps of reaction. A synthetic route of the 5-fluoro-2-(1-bromocyclopropyl) pyridine is as follows: (as described in the specification). The invention has the advantages that the synthesis method of 5-fluoro-2-(1-bromocyclopropyl) pyridine improves the yield and provides an efficient synthesis method for the synthesis of the compound.
An Intramolecular Cycloaddition Approach to the Kauranoid Family of Diterpene Metabolites
Callebaut, Brenda,Hullaert, Jan,Van Hecke, Kristof,Winne, Johan M.
supporting information, p. 310 - 314 (2019/01/10)
Synthetic studies toward the ent-kauranoid family of diterpene natural products are reported. An intramolecular (4 + 3) cycloaddition allows the direct elaboration of diverse natural product frameworks, encompassing a challenging bicyclo[3.2.1]octane core. The established routes comprise only a few synthetic operations (3-5 steps), transforming a range of simple starting materials into the tetracyclic scaffolds that are commonly found in many ent-kaurene metabolites.
Transition-Metal-Free Access to Heteroaromatic-Fused 4-Tetralones by the Oxidative Ring Expansion of the Cyclobutanol Moiety
Natho, Philipp,Allen, Lewis A. T.,White, Andrew J. P.,Parsons, Philip J.
, p. 9611 - 9626 (2019/08/16)
Advances in the transition-metal-free cyclobutanol ring expansion to 4-tetralones under N-bromosuccinimide mediation are described. We have expanded the scope of this ring expansion methodology and investigated the effect substituents on the aromatic ring, and the cyclobutanol moiety, have on the outcome of the reaction. Limitations with certain substituents on the cyclobutanol moiety are also described. Further experimental evidence to support our mechanistic understanding is disclosed, and we now preclude the suggested involvement of a primary radical for this transformation.