98475-07-1Relevant articles and documents
Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl and noradamantyl phthalimidines for nitrite, TNF-α and angiogenesis inhibitory activities
Luo, Weiming,Tweedie, David,Beedie, Shaunna L.,Vargesson, Neil,Figg, William D.,Greig, Nigel H.,Scerba, Michael T.
, p. 1547 - 1559 (2018)
A library of 15 novel and heretofore uncharacterized adamantyl and noradamantyl phthalimidines was synthesized and evaluated for neuroprotective and anti-angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected reductions in levels of secreted TNF-α and nitrite relative to basal amounts. The primary SAR suggests nitration of adamantyl phthalimidines has marginal effect on TNF-α activity but promotes anti-nitrite activity; thioamide congeners retain anti-nitrite activity but are less effective reducing TNF-α. Site-specific nitration and thioamidation provided phthalimidine 24, effecting an 88.5% drop in nitrite concurrent with only a 4% drop in TNF-α. Notable anti-angiogenesis activity was observed for 20, 21 and 22.
One-pot method to construct isoindolinones and its application to the synthesis of DWP205109 and intermediate of Lenalidomide
Liu, Jinbiao,Lu, Bowei,Lu, Junrui,Wang, Hongbo,Xie, Zhiqiang,Zhong, Kaikai
supporting information, (2021/06/07)
Herein a practical and efficient system for concise synthesis of isoindolinones is described by using substituted methyl 2-(halomethyl)benzoates and substituted amines. Structurally various methyl 2-(halomethyl)benzoates and amines were transformed into isoindolinones 80–99% yield and purity in catalyst-free and solvent-free conditions. The method has a wide substrate scope. The synthetic utility of the one-pot reaction was demonstrated by the concise syntheses of Lenalidomide intermediate and DWP205190.
Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands
Bricelj, Ale?a,Dora Ng, Yuen Lam,Ferber, Dominic,Gütschow, Michael,Kr?nke, Jan,Kuchta, Robert,Müller, Sina,Monschke, Marius,Sosi?, Izidor,Steinebach, Christian,Wagner, Karl G.
supporting information, p. 1733 - 1738 (2021/11/16)
Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.
Compound for targeted degradation of BTK protein
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Paragraph 0458-0464, (2021/06/22)
The invention provides a compound with the capability of degrading Bruton's tyrosine protein kinase (Btk) protein in a targeted manner, and particularly provides a compound as shown in the following formula I0, wherein the definition of each group is described in the specification. The compound provided by the invention can well degrade Btk protein in a targeted manner, so that the compound can be used for treating diseases related to Btk activity or expression quantity, such as tumors.
Method for synthesizing lenalidomide
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Paragraph 0024; 0027; 0030-0031, (2020/01/12)
The invention belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing lenalidomide. The method adopts three-step polymerization, and specifically comprises: (1) carrying out a bromination reaction on 2-methyl-3-nitromethyl benzoate as a starting raw material and a bromination reagent to generate a compound 1 2-bromomethyl-3-nitromethyl benzoate; (2) performing cyclization on the compound 1 and 3-aminopiperidine-2,6-dione hydrochloride under a solvent-free condition to generate a compound 2 3-(4-nitro-1-oxo-1,3-dihydroisoindole-2-yl)piperidine-2,6-dione; and (3) reducing the compound 2 with a reducing agent to obtain lenalidomide. According to the invention, the method is a novel preparation process method of lenalidomide, and has advantages of easily available process raw materials, short steps, simple and convenient operation, environmental friendliness, implementation value of industrial production, and social and economic benefits.
Efficient synthesis of dibenzazepine lactams via a sequential Pd-catalyzed amination and aldol condensation reaction
Song, Ha-Jeong,Yoon, Eunyoung,Heo, Jung-Nyoung
supporting information, (2019/12/27)
A simple and efficient reaction was developed for the synthesis of dibenzazepine lactam derivatives. The core 7-membered azepine ring was formed by a stepwise sequence involving a palladium-catalyzed amination and an aldol condensation.
Compound with dual inhibitory activity TDO, IDOO1 and application of compound for treating neurodegenerative disease (by machine translation)
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Paragraph 0149; 0184-0189, (2020/10/06)
The present invention provides a compound of formula I, or a pharmaceutically acceptable salt thereof, or a solvate thereof, which can selectively inhibit TDO, IDOO1, which has a significant inhibitory effect on TDO and/or IDOO1. In addition, the prepared compound has a remarkable anti-tumor effect, has a certain treatment effect on's disease and's disease, and has a good application prospect in the field of medicine preparation. (by machine translation)
Preparation method of lenadomide
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Paragraph 0031; 0033-0034, (2019/06/07)
The invention discloses a preparation method of lenalidomide, and belongs to the field of organic synthesis. 2-methyl-3-methyl nitrobenzoate and 3-N-benzyloxy-carbonyl-L-glutamine serve as starting materials, and an important intermediate 2-brooethyl-3-methyl nitrobenzoate is obtained through a bromination reaction of 2-methyl-3-methyl nitrobenzoate. 3-N-benzyloxy-carbonyl-L-glutamine is cyclizedunder catalysis to produce 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine, an amino group is subjected to deprotection to produce 3-amino-2,6-piperidone halide, 3-(4-nitro-1-oxo-1,3-o-xylylenimine-2-yl)piperidine-2,6-diketone is obtained through an aminolysis reaction of 3-N-benzyloxy-carbonyl-2,6-dioxopiperidine and 2-brooethyl-3-methyl nitrobenzoate, and then lenalidomide is prepared through reduction. The method has the advantages that the cost of raw materials are low, aftertreatment is simple, and the yield is high, and the production cost of the lenalidomide as a bulk drug is greatly reduced. The method is a convenient and efficient lenalidomide synthesis method suitable for industrial production.
PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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Page/Page column 120, (2019/11/12)
The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
Water-soluble, stable and azide-reactive strained dialkynes for biocompatible double strain-promoted click chemistry
Sharma, Krishna,Strizhak, Alexander V.,Fowler, Elaine,Wang, Xuelu,Xu, Wenshu,Hatt Jensen, Claus,Wu, Yuteng,Sore, Hannah F.,Lau, Yu Heng,Hyv?nen, Marko,Itzhaki, Laura S.,Spring, David R.
supporting information, p. 8014 - 8018 (2019/09/06)
The Sondheimer dialkyne is extensively used in double strain-promoted azide-alkyne cycloadditions. This reagent suffers with poor water-solubility and rapidly decomposes in aqueous solutions. This intrinsically limits its application in biological systems, and no effective solutions are currently available. Herein, we report the development of novel highly water-soluble, stable, and azide-reactive strained dialkyne reagents. To demonstrate their extensive utility, we applied our novel dialkynes to a double strain-promoted macrocyclisation strategy to generate functionalised p53-based stapled peptides for inhibiting the oncogenic p53-MDM2 interaction. These functionalised stapled peptides bind MDM2 with low nanomolar affinity and show p53 activation in a cellular environment. Overall, our highly soluble, stable and azide-reactive dialkynes offer significant advantages over the currently used Sondheimer dialkyne, and could be utilised for numerous biological applications.
