CAS: 1229705-06-9; 4-((2R,3S,4R,5S)-3-(3-Chloro-2-Fluorophenyl)-4-(4-Chloro-2-Fluorophenyl)-4-Cyano-5-Neopentylpyrrolidine-2-Carboxamido)-3-Methoxybenzoic Acid

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(Z)-3-(3-chloro-2-fluorophenyl)-2-(4-chloro-2-fluorophenyl)prop-2-enenitrile 2-[(E)-(3,3-dimethylbutylidene)amino]acetic acid tert-butyl ester 2-(4-chloro-2-fluoro-phenyl)acetonitrile 2-fluoro-3-chlorobenzaldehyde4-[(5S,6R,7S,7aR)-7-(3-chloro-2-fluorophenyl)-6-(4-chloro-2-fluorophenyl)-6-cyano-5-(2,2-dimethylpropyl)-1-oxo-tetrahydropyrrolo[1,2-c]imidazol-2-yl]-3-methoxybenzoic acid 4-[(5S,6R,7S,7aR)-7-(3-chloro-2-fluorophenyl)-6-(4-chloro-2-fluorophenyl)-6-cyano-5-(2,2-dimethylpropyl)-1-oxo-tetrahydropyrrolo[1,2-c]imidazol-2-yl]-3-methoxybenzamide 2-((1-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)ethoxy)carbonylamino)acetic acid 1-(cyclohexyloxycarbonyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate

📜4-{[(2R,3S,4R,5S)-3-(3-Chloro-2-Fluorophenyl)-4-(4-Chloro-2-Fluorophenyl)-4-Cyano-5-(2,2-Dimethylpropyl)Pyrrolidine-2-Carbonyl]Amino}-3-Methoxybenzoic Acid Methyl Ester置于水,Sodium Hydroxide体系中,用 四氢呋喃,乙醇 用作溶剂,化学反应 18.0H,以118 Mg的收率获得idasanutlin(4-((2R,3S,4R,5S)-3-(3-氯-2-氟苯基)-4-(4-氯-2-氟苯基)-4-氰基-5-新戊基吡咯烷-2-甲酰胺)-3-甲氧基苯甲酸;)
参考文献:Photoactivation Of Mdm2 Inhibitors: Controlling Protein-protein Interaction With Light
标题:Photoactivation Of Mdm2 Inhibitors: Controlling Protein-protein Interaction With Light
摘要:Selectivity Remains A Major Challenge In Anticancer Therapy,Which Potentially Can Be Overcome By Local Activation Of A Cytotoxic Drug. Such Triggered Activation Can Be Obtained Through Modification Of A Drug With A Photoremovable Protecting Group (Ppg),And Subsequent Irradiation In The Chosen Place And Time. Herein,The Design,Synthesis And Biological Evaluation Is Described Of A Photoactivatable Mdm2 Inhibitor,Ppg-Idasanutlin,Which Exerts No Functional Effect On Cellular Outgrowth,But Allows For The Selective,Noninvasive Activation Of Antitumor Properties Upon Irradiation Visible Light,Demonstrating Activation With Micrometer,Single Cell Precision. The Generality Of This Method Has Been Demonstrated By Growth Inhibition Of Multiple Cancer Cell Lines Showing P53 Stabilization And Subsequent Growth Inhibition Effects Upon Irradiation. Light Activation To Regulate Protein-Protein Interactions Between Mdm2 And P53 Offers Exciting Opportunities To Control A Multitude Of Biological Processes And Has The Potential To Circumvent Common Selectivity Issues In Antitumor Drug Development.
Doi:10.1021/jacs.8B04870

专利信息

专利号:WO-2025061648-A1
优先权日:2023-09-18
标题:Targeting the c-myc/mdm2 pathway for the treatment of proliferative disorders
发明人：FAHRAEUS ROBIN; SALOMAO NORMAN; HABAULT JUSTINE
权利人:INST NAT SANTE RECH MED; UNIV PARIS CITE; HOPITAUX PARIS ASSIST PUBLIQUE
摘要:Using a Burkitt's lymphoma (BL) cell model, the present inventors have shown that it is possible to suppress the synthesis of c-Myc by using specific compounds that bind to MDM2. The present inventors have shown that under low-cell proliferation conditions, MDM2 binds to the 5' untranslated region (UTR) of the c-Myc mRNA and suppresses its synthesis in a p53-independent manner, but 5 that this interaction does not take place under under medium/high cell proliferation conditions due to a conformational change in MDM2. The inventors have shown that under such conditions, it is possible to use specific MDM2-binding agents that induce an allosteric transition of MDM2 to promote its ability to interact with c-Myc mRNA, thereby suppressing its expression. The present invention therefore pertains to an MDM2-binding agent for use in the treatment of a proliferative disorder, 10 wherein said agent restores the c-Myc binding conformation of MDM2 and wherein said proliferative disorder is a p53-mutated disorder.

专利号:US-2023037284-A9
优先权日:2018-11-30
标题:Combination therapy of peptidomimetic macrocycles
发明人：GUERLAVAIS VINCENT; ANNIS DAVID ALLEN
权利人:AILERON THERAPEUTICS INC
摘要:The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

专利号:US-12441733-B2
优先权日:2018-03-26
标题:Substituted 2,4-dioxotetrahydropyrimidines as intermediates in the synthesis of bruton's tyrosine kinase inhibitors
发明人：ARISTA LUCA; HEBACH CHRISTINA; HOLLINGWORTH GREGORY JOHN; HOLZER PHILIPP; IMBACH-WEESE PATRICIA; LORBER JULIEN; MACHAUER RAINER; SCHMIEDEBERG NIKO; VULPETTI ANNA; ZOLLER THOMAS
权利人:NOVARTIS AG
摘要:The invention relates to compounds of the formulae (I), (III), (IIIa), (XXIa), (XXIII), and/or (XLVI)or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to use of the compounds in the treatment of disease.

专利号:US-9828340-B2
优先权日:2013-02-21
标题 :Asymmetric synthesis of a substituted pyrrolidine-2-carboxamide
发明人：FISHLOCK DANIEL; GU CHEN; SHU LIANHE; REGE PANKAJ DEVDATTA; SARMA KESHAB
权利人:HOFFMANN LA ROCHE
摘要:The invention relates to a process for the preparation of 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid of the formula (I) n nas well as intermediates thereof and pharmaceutical preparations thereof, comprising the step of reacting a compound of the formula (IV) with a compound of the formula (V), as defined in the specification, in the presence of a chiral silver- or copper catalyst.

专利号:US-2018371021-A1
优先权日:2017-05-11
标 题 :Peptidomimetic macrocycles and uses thereof
发明人：AIVADO MANUEL; GUERLAVAIS VINCENT; OLSON KAREN
权利人:AILERON THERAPEUTICS INC
摘要:The present disclosure describes the synthesis of peptidomimetic macrocycles and methods of using peptidomimetic macrocycles to treat a condition. The present disclosure also describes methods of using peptidomimetic macrocycles in combination with at least one additional pharmaceutically-active agent for the treatment of a condition, for example, cancer.

专利号:CA-2894826-C
优先权日:2013-02-21
标 题:Asymmetric synthesis of a substituted pyrrolidine-2-carboxamide