- NOVEL HETEROCYCLIC COMPOUNDS
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The invention provides novel heterocyclic compounds having thegeneral formula (I), and pharmaceutically acceptable salts thereof, wherein R1 to R4, m, n, and p are as described herein. Formula (I). Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.
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Page/Page column 52; 94
(2021/07/31)
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- Design, Synthesis, and Evaluation of Lipopeptide Conjugates of Mercaptoundecahydrododecaborate for Boron Neutron Capture Therapy
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We developed new 10B carriers for boron neutron capture therapy (BNCT) that can effectively transport and accumulate boron clusters into cells. These carriers consist of a lipopeptide, mercaptoundecahydrododecaborate (BSH), and a disulfide linker. The carriers were conceived according to the structure of pepducin, a membrane-penetrating lipopeptide targeting protease-activated receptor 1 (PAR1). To improve the membrane permeability of BSH, the structure was optimized using various lipopeptides possessing different peptides and lipid moieties. These synthesized lipopeptides were conjugated with BSH and evaluated for intracellular uptake using T98G glioblastoma cells. Among them, the most effectively incorporated and accumulated in the cells was compound 5 a, which contains a peptide of 13 residues derived from the intracellular third loop of PAR1 and a palmitoyl group. For further improvement of 10B accumulation in cells, the introduction of an amine linker was investigated; intracellular uptake similar to that of 5 a was observed for compound 14, which has a piperazine linker. Both compounds 5 a and 14 showed a stronger radiosensitizing effect than BSH along on T98G cells under mixed-neutron beam irradiation. The results demonstrate that lipopeptide conjugation is effective for enhancing intracellular delivery and accumulation of BSH and improving the cytotoxic effect of BNCT.
- Isono, Aoi,Tsuji, Mieko,Sanada, Yu,Matsushita, Akari,Masunaga, Shinichiro,Hirayama, Tasuku,Nagasawa, Hideko
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supporting information
(2019/03/07)
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- Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on ibrutinib: A comparative study
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Ibrutinib is a covalent and irreversible inhibitor of Bruton's tyrosine kinase (BTK) and has been approved for the treatment of haematological malignancies, such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenstr?m's macroglobulinemia. The covalent and irreversible nature of its molecular mode of action allows identification and monitoring of its target in an activity-based protein profiling (ABPP) setting. Fluorescent and biotinylated ibrutinib derivatives have appeared in the literature in recent years to monitor BTK in vitro and in situ. The work described here complements this existing methodology and pertains a comparative study on the efficacy of direct and two-step bioorthogonal ABPP of BTK.
- Liu, Nora,Hoogendoorn, Sascha,Van De Kar, Bas,Kaptein, Allard,Barf, Tjeerd,Driessen, Christoph,Filippov, Dmitri V.,Van Der Marel, Gijsbert A.,Van Der Stelt, Mario,Overkleeft, Herman S.
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p. 5147 - 5157
(2015/05/13)
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- Synthesis of 1-substituted-6-methyluracils.
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A series of 6-methyl-1H-pyrimidin-2,4-diones bearing different substituents in the 1-position of the uracil ring were prepared starting from substituted ureas and diketene.
- Nieto, Rosa Maria,Coelho, Alberto,Martinez, Ana,Stefanachi, Angela,Sotelo, Eddy,Ravina, Enrique
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p. 1025 - 1028
(2007/10/03)
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- Anthrapyrazole anticancer agents. Synthesis and structure-activity relationships against murine leukemias
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Chromophore modification of the anthracenediones related to mitoxantrone in an attempt to provide agents with diminished or no cardiotoxicity has resulted in a novel class of DNA binders, the anthrapyrazoles. Their synthesis was carried out by a two-stage
- Showalter,Johnson,Hoftiezer,Turner,Werbel,Leopold,Shillis,Jackson,Elslager
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p. 121 - 131
(2007/10/02)
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- Antimicrobial substituted anthra[1,9-cd]pyrazol-6(2H)-ones
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Substituted anthra[1,9-cd]pyrazol-6(2H-ones have antimicrobial activity. Methods for their preparation, use and pharmaceutical compositions are disclosed.
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