13730-55-7Relevant academic research and scientific papers
A Selective Receptor for Arginine Derivatives in Aqueous Media. Energetic Consequences of Salt Bridges That Are Highly Exposed to Water
Ngola, Sarah M.,Kearney, Patrick C.,Mecozzi, Sandro,Russell, Keith,Dougherty, Dennis A.
, p. 1192 - 1201 (1999)
Quantitative measures of salt-bridge-type interactions in a highly exposed aqueous environment have been obtained by modifying the well-studied cyclophane platform 1 to include carboxylates in close proximity to bound, cationic guests, producing hosts 2 and 3. Many guests show significantly enhanced binding to 2 and 3, but cations of the RNMe3+ type show little or no enhancement. We propose that the latter observations result from the fact that RNMe3+ compounds have very diffuse positive charges. Guests that show enhanced binding have focused regions of large, positive electrostatic potential. The highly charged 3 is able to bind very polar, very well-solvated guests, including a series of arginine-based dipeptides. Neutral, water-soluble host 4 was prepared and found to show a decreased affinity for cationic guests. We propose a novel induced dipole mechanism to rationalize these results.
Copper-promoted direct amidation of isoindolinone scaffolds by sodium persulfate
Lai, Huifang,Lin, Jin,Xu, Jiexin,Zha, Daijun
supporting information, p. 7621 - 7626 (2021/09/22)
Isoindolinones are ubiquitous structural motifs in natural products and pharmaceuticals. Establishing an efficient method for structural modification of isoindolinones could significantly facilitate new drug development. Herein, we describe copper-promoted direct amidation of isoindolinone scaffolds mediated by sodium persulfate. The method exhibits mild reaction conditions and high site-selectivity, and enables the structural modification of the drug indobufen ester with various amides with yields of 49 to 98%. It is also gram-scalable. Additionally, the reaction mechanism appears to involve a radical and a carbocationic pathway.
Novel PTP1B enzyme inhibitor, preparation method and applications thereof
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Paragraph 0081; 0140-0141, (2017/08/31)
The present invention provides a novel PTP1B enzyme inhibitor, a preparation method and applications thereof, and particularly discloses a class of bis 2-substituted ethylene sulfonate compounds and a preparation method thereof, and uses of the bis 2-substituted ethylene sulfonate compounds as the PTP1B enzyme activity inhibitor. According to the present invention, the prepared novel compound has good PTP1B enzyme activity inhibition effect, and has the application value in preparation of drugs for treatment and prevention of diabetes and obesity.
Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations
Nicolaou,Wang, Yanping,Lu, Min,Mandal, Debashis,Pattanayak, Manas R.,Yu, Ruocheng,Shah, Akshay A.,Chen, Jason S.,Zhang, Hongjun,Crawford, James J.,Pasunoori, Laxman,Poudel, Yam B.,Chowdari, Naidu S.,Pan, Chin,Nazeer, Ayesha,Gangwar, Sanjeev,Vite, Gregory,Pitsinos, Emmanuel N.
supporting information, p. 8235 - 8246 (2016/07/15)
From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy.
New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: Synthesis, anti-HIV-1 evaluation and binding affinities
Poty, Sophie,Désogère, Pauline,Goze, Christine,Boschetti, Frédéric,D'huys, Thomas,Schols, Dominique,Cawthorne, Christopher,Archibald, Stephen J.,Ma?cke, Helmut R.,Denat, Franck
, p. 5004 - 5016 (2015/03/18)
CXCR4 is a target of growing interest for the development of new therapeutic drugs and imaging agents as its role in multiple disease states has been demonstrated. AMD3100, a CXCR4 chemokine receptor antagonist that is in current clinical use as a haematopoietic stem cell mobilising drug, has been widely studied for its anti-HIV properties, potential to inhibit metastatic spread of certain cancers and, more recently, its ability to chelate radiometals for nuclear imaging. In this study, AMD3100 is functionalised on the phenyl moiety to investigate the influence of the structural modification on the anti-HIV-1 properties and receptor affinity in competition with anti-CXCR4 monoclonal antibodies and the natural ligand for CXCR4, CXCL12. The effect of complexation of nickel(ii) in the cyclam cavities has been investigated. Two amino derivatives were obtained and are suitable intermediates for conjugation reactions to obtain CXCR4 molecular imaging agents. A fluorescent probe (BODIPY) and a precursor for 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents.
DERIVATIVES OF UNCIALAMYCIN, METHODS OF SYNTHESIS AND THEIR USE AS ANTITUMOR AGENTS
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Page/Page column 91, (2015/02/25)
In one aspect, the present disclosure provides new analogs of uncialamycin of formulae (I) and (II). The present disclosure also provides novel synthetic pathways to obtaining uncialamycin and analogs thereof. Additionally, the present disclosure also describes methods of use of uncialamycin and analogs thereof. In another aspect, the present disclosure provides antibody-drug conjugates comprising the compounds of formulae (I) and (ll).
Isosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity
Ruchelman, Alexander L.,Man, Hon-Wah,Zhang, Weihong,Chen, Roger,Capone, Lori,Kang, Jian,Parton, Anastasia,Corral, Laura,Schafer, Peter H.,Babusis, Darius,Moghaddam, Mehran F.,Tang, Yang,Shirley, Michael A.,Muller, George W.
, p. 360 - 365 (2013/02/23)
A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide (2), in which the amino group is replaced with various isosteres, was prepared and assayed for immunomodulatory activity and activity against cancer cell lines. The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent inhibition of tumor necrosis factor-α (TNF-α) in LPS-stimulated hPBMC, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against the Namalwa lymphoma cell line. Both of these analogs displayed oral bioavailability in rat.
Planar-to-planar chirality transfer in the excited state. Enantiodifferentiating photoisomerization of cyclooctenes sensitized by planar-chiral paracyclophane
Maeda, Ryo,Wada, Takehiko,Mori, Tadashi,Kono, Shigeyuki,Kanomata, Nobuhiro,Inoue, Yoshihisa
supporting information; experimental part, p. 10379 - 10381 (2011/09/13)
Photochemical planar-to-planar chirality transfer was effected by using (R)-[10]paracyclophane-12-carboxylates as a planar-chiral sensitizer and (Z)-cyclooctene and (Z,Z)-1,5-cyclooctadiene as prochiral substrates to give a planar-chiral (E)- and (E,Z)-isomer in up to 44% and 87% enantiomeric excess, respectively, the latter of which being the highest ever reported for a sensitized photochirogenic reaction.
OXYGEN SCAVENGING MOLECULES, ARTICLES CONTAINING SAME, AND METHODS OF THEIR USE
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Page/Page column 13, (2011/10/19)
The invention relates to compounds of the structure of formula I and II: where X is selected from the group consisting of O, S and NH; Y, A and B are independently selected from the group consisting of N and CH; D, E and F are independently selected from the group consisting of CH, N, O and S; the symbol represents a single or a double bond; and R1, R2 and R3 are independently selected from the group consisting of H, electron withdrawing groups and electron releasing groups. In other embodiments, the compounds are used as oxygen scavengers and in barrier compositions and articles.
Computational and experimental structure-reactivity relationships: evidence for a side reaction in Alpine-Borane reductions of d-benzaldehydes
Zhu, Hui,Soledad Reyes,Meyer, Matthew P.
supporting information; experimental part, p. 6803 - 6806 (2010/04/29)
Extraordinary stereoselectivity, approaching 100%, has been reported in the reductions of d-benzaldehydes by B-isopinocampheyl-9-borabicyclo[3.3.1]nonane (Alpine-Borane). This is likely because of the extreme size disparity of groups on either side of the carbonyl. Here, we present a structure-reactivity study whereby the reductions of variably substituted d-benzaldehydes are explored using highly sensitive measures for enantiomeric excess and relative reactivity. These results are compared to the relative rates predicted from density functional calculations. The results indicate that 2,6-disubstitution adversely affects the stereoselectivity by means of a non-selective reduction via the dehydroboration product of Alpine-Borane, 9-borabicyclo[3.3.1]nonane.
