- Preparation method of XPO-1 inhibitor
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The invention provides a preparation method of an XPO-1 inhibitor. Specifically, a compound II is prepared from a compound I and pinacol diborate under the action of a Grignard reagent, then the compound II reacts with a compound III under the action of a catalyst and alkali to obtain a compound IV, the compound IV and a compound V are condensed and then hydrolysis is conducted to obtain a compound VI, and finally the final product Eltanexor is prepared through a mixed anhydride method. The preparation method has the advantages of simple and safe synthesis route and operation, easily available raw materials, simple post-treatment and high yield, and is suitable for industrial production.
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Paragraph 0103-0105
(2022/01/12)
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- Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids
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Boronic acids are an increasingly important compound class for many applications, including C-C bond formation reactions, medicinal chemistry, and diagnostics. The deprotection of boronic ester intermediates is frequently a problematic and inefficient step in boronic acid syntheses. We describe an approach that highly facilitates this transformation by leveraging the volatility of methylboronic acid and its diol esters. The method is performed under mild conditions, provides high yields, and eliminates cumbersome and problematic purification steps.
- Hinkes, Stefan P.A.,Klein, Christian D.P.
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supporting information
p. 3048 - 3052
(2019/05/10)
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- A Monophosphine Ligand Derived from Anthracene Photodimer: Synthetic Applications for Palladium-Catalyzed Coupling Reactions
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Herein, we present an air-stable dianthracenyl monophosphine ligand (diAnthPhos) which can be prepared in two steps from commercially available anthracene derivatives. The ligand exhibits excellent efficiency for palladium-catalyzed coupling reactions. In particular, Miyaura borylation of heterocycle-containing electrophiles can be facilitated employing the diAnthPhos ligand with a broad substrate scope and low catalyst loading. The valuable synthetic utility of the new ligand is further demonstrated by a one-pot Miyaura borylation/Suzuki coupling protocol for heteroaryl-containing substrates.
- Wang, Xin,Liu, Wei-Gang,Tung, Chen-Ho,Wu, Li-Zhu,Cong, Huan
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supporting information
p. 8158 - 8163
(2019/09/07)
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- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 001138-001139
(2018/11/22)
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- Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1
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Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analogue synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.
- Gazzard, Lewis,Williams, Karen,Chen, Huifen,Axford, Lorraine,Blackwood, Elizabeth,Burton, Brenda,Chapman, Kerry,Crackett, Peter,Drobnick, Joy,Ellwood, Charles,Epler, Jennifer,Flagella, Michael,Gancia, Emanuela,Gill, Matthew,Goodacre, Simon,Halladay, Jason,Hewitt, Joanne,Hunt, Hazel,Kintz, Samuel,Lyssikatos, Joseph,Macleod, Calum,Major, Sarah,Médard, Guillaume,Narukulla, Raman,Ramiscal, Judi,Schmidt, Stephen,Seward, Eileen,Wiesmann, Christian,Wu, Ping,Yee, Sharon,Yen, Ivana,Malek, Shiva
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p. 5053 - 5074
(2015/07/02)
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- Iridium-catalyzed C-H borylation of heteroarenes: Scope, regioselectivity, application to late-stage functionalization, and mechanism
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A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were found to be amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodology for the synthesis of complex heteroaryl structures. Application of this methodology to the synthesis and late-stage functionalization of biologically active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen.
- Larsen, Matthew A.,Hartwig, John F.
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supporting information
p. 4287 - 4299
(2014/04/03)
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- KINASE INHIBITOR COMPOUNDS
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Pyridine and pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
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Page/Page column 38
(2008/12/07)
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