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  • 1. Aahlin, Kristofer
    et al.
    Arvidsson, Per I.
    Huerta, Fernando
    Yngve, Ulrika.
    Preparation of 1-(4-(5-amino-6-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-yl)benzoyl)piperazine derivatives as glycogen synthase kinase 3 inhibitors.2011Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. I [R1 = H or Me], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase 3 (GSK3) inhibitors. Thus, e.g., II was prepd. by cyclization of 3-amino-N-(4-hydroxypyridin-3-yl)pyrazine-2-carboxamide (prepn. given) to get intermediate 3-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-amine, which underwent bromination followed by Suzuki reaction with (4-methylpiperazin-1-yl)(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone. Compds. of the invention were tested for their selective inhibitory activity of GSK3β, e.g., II exhibited Ki value of 2.3 nM. The invention compds. are useful for the treatment of cognitive disorders, diabetes, cancer, etc. [on SciFinder(R)]

  • 2. Arvidsson, Per
    et al.
    Burrows, Jeremy
    Soederman, Peter
    Yngve, Ulrika.
    Preparation of arylimidazopyridine derivatives for use as GSK3 modulators.2008Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. I [A = (un)substituted aryl or heteroaryl; Q = halo; R1 = C(O)NR6R7; R2 and R4 independently = H, halo, CN, NO2, alkyl, or haloalkyl; R3 and R5 independently = H, halo, alkyl, or haloalkyl; R6 and R7 = together with the atoms to which they are attached form an (un)substituted heterocyclic ring contg. one or more heteroatoms selected from N, O, or S;], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase-3 (GSK3) modulators. Thus, e.g., II•HCl was prepd. by cyclocondensation of 5-bromopyridine-2,3-diamine with terephthalic monomethyl ester followed by chlorination, iodination, sapon., amidation with N-methylpiperazine, and coupling with 4-methoxyphenyl boronic acid. I were evaluated in GSK3β scintillation proximity assays, e.g., II•HCl demonstrated an Ki value of 97 nM. [on SciFinder(R)]

  • 3. Arvidsson, Per
    et al.
    Burrows, Jeremy
    Soederman, Peter
    Yngve, Ulrika.
    Preparation of imidazopyridinecarboxamide derivatives for use as GSK3 modulators.2008Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. I [Q = halo; R1 = CH2NR3R4; each R2 independently = H or alkyl; R3 and R4 = together with the atoms to which they are attached form an (un)substituted heterocyclic ring contg. one or more heteroatoms selected from N, O, or S; R6 = H or alkyl; R7 = H, (un)substituted alkyl, alkylaryl, aryl, or heteroaryl], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase-3 (GSK3) modulators. Thus, e.g., II•HCl was prepd. by cyclocondensation of 5-bromopyridine-2,3-diamine with terephthalic monomethyl ester followed by chlorination, iodination, sapon., amidation with morpholine, redn., and coupling with carbon monoxide and 3-methoxy-1-propanamine. I were evaluated in GSK3β scintillation proximity assays, e.g., II•HCl demonstrated an Ki value of 390 nM. [on SciFinder(R)]

  • 4. Besidski, Yevgeni
    et al.
    Yngve, Ulrika
    Paulsen, Kim
    Linde, Christian
    Macsari, Istvan
    Malmborg, Jonas
    Paptchikhine, Alexander
    Arvidsson, Per.
    Preparation of pyrimidinylamine compounds as gamma secretase modulators useful for treatment of Aβ-related diseases.2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The invention relates to pyrimidinylamine compds. of formula I and pharmaceutically acceptable salts and pharmaceutical compns. thereof, as well as processes for making these compds. for use in the treatment and/or prevention of Aβ-related diseases. I [wherein A is (un)substituted 5- or 6-membered heteroaryl ring comprising at least one N; R1 is H, C1-3-alkyl, cyano, etc.; R2 and R3 are each independently selected from C1-3-alkyl and fluoro-C1-3-alkyl; or R2 and R3 together with the carbon to which they are attached form a 3- to 6-membered satd. carbocyclic ring, optionally substituted with one or more fluoro substituents; R4 is C1-3-alkyl, fluoro-C1-3-alkyl, or C3-6-cycloalkyl-C1-3-alkyl; R5 is H, C1-3-alkyl, fluoro, etc.; R6 is, for example, CH3NH-, CNCH2-, or MeO-] or pharmaceutically acceptable salts thereof are claimed and exemplified. Example compd. II was prepd. from the reaction of III with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline under Buchwald-Hartwig conditions in 77% yield. Fifty-two compds. of I were evaluated for activity on Aβ formation utilizing electrochemiluminescence anal. and HEK cells expressing amyloid precursor protein (data given). [on SciFinder(R)]

  • 5. Besidski, Yevgeni
    et al.
    Yngve, Ulrika
    Paulsen, Kim
    Linde, Christian
    Malmborg, Jonas.
    Preparation of aminotriazole compounds as gamma secretase modulators useful for treatment of Aβ-related diseases.2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The invention relates to aminotriazole compds. of formula I and pharmaceutically acceptable salts and pharmaceutical compns. thereof, as well as processes for making these compds. for use in the treatment and/or prevention of Aβ-related diseases. I [wherein A is (un)substituted 5- or 6-membered heteroaryl ring comprising at least one N; R1 is H, C1-3-alkyl, cyano, etc.; R2 is (un)substituted C1-6-alkyl, C3-7-cycloalkyl-C1-3-alkyl, heterocyclyl-C1-3-alkyl, etc.; R3 and R4 are each independently selected from H, C1-6-alkyl, (un)substituted C3-7-cycloalkyl, etc.] or pharmaceutically acceptable salts thereof are claimed and exemplified. Example compd. II was prepd. from the reaction of 3-bromo-N-(cyclopropylmethyl)-1-methyl-1H-1,2,4-triazol-5-amine with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline dihydrochloride under Buchwald-Hartwig conditions in 26% yield. Nine compds. of I were evaluated for inhibition of Aβ formation utilizing electrochemiluminescence anal. and HEK cells expressing amyloid precursor protein (data given). [on SciFinder(R)]

  • 6. Besidski, Yevgeni
    et al.
    Yngve, Ulrika
    Paulsen, Kim
    Linde, Christian
    Nordvall, Gunnar
    Macsari, Istvan
    Malmborg, Jonas.
    Preparation of azetidinotriazole compounds as gamma secretase modulators useful for treatment of Aβ-related diseases.2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The invention relates to azetidinotriazole compds. of formula I and pharmaceutically acceptable salts and pharmaceutical compns. thereof, as well as processes for making these compds. for use in the treatment and/or prevention of Aβ-related diseases. I [wherein A is (un)substituted 5- or 6-membered heteroaryl ring comprising at least one N; R1 is H, C1-3-alkyl, cyano, etc.; R2 is (un)substituted C1-6-alkyl, C3-7-cycloalkyl-C1-3-alkyl, heterocyclyl-C1-3-alkyl, etc.; R3, R5, and R7 are each independently selected from H, (un)substituted C1-3-alkyl, C3-7-cycloalkyl, etc.; R4, R6, R8 are each independently selected from H, F, C1-3-alkyl, etc.; or R3 and R4, or R5 and R6, or R7 and R8, together with the carbon to which they are attached, form (un)substituted 3- to 7-membered satd. ring optionally contg. an O or N] or pharmaceutically acceptable salts thereof are claimed and exemplified. Example compd. II was prepd. from the reaction of III with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline under Buchwald-Hartwig conditions in 26% yield. Nine compds. of I were evaluated for activity on Aβ formation utilizing electrochemiluminescence anal. and HEK cells expressing amyloid precursor protein (data given). [on SciFinder(R)]

  • 7. Burrows, Jeremy
    et al.
    Huerta, Fernando
    Lake, Fredrik
    Pedersen, Torben
    Rein, Tobias
    Rotticci, Didier
    Staaf, Karin
    Yngve, Ulrika.
    Preparation of imidazolyl-pyrimidine derivatives as GSK3 inhibitors.2008Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. I [R1 = sulfamoyl, carbamoyl or -R5-R6 and N linked (un)substituted 4- to 7-membered satd. ring which optionally contains an addnl. N, O or S; R5 = O, C(O), C(O)O, C(O)NH, etc., R6 = (un)substituted alkyl, carbocyclyl or heterocyclyl; at least one of X1, X2, X3 and X4 = N, the other three independently = N or C(R9), wherein R9 = H, halo, CN, OH, NH2, alkyl or alkoxy; provided that not more than two of X1, X2, X3 or X4 = N; R2 = halo or CN; R3 = Me, (un)substituted 3-tetrahydropyranyl or 4-tetrahydropyranyl; R4 = H, halo, CN or (un)substituted alkyl], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase 3 (GSK3) inhibitors. Thus, e.g., II was prepd. by amidation of 3,5-dichloro-2-pyridinecarboxylic acid with piperidine followed by coupling reaction with 5-fluoro-4-[2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine, which was prepd. starting from 5-methyl-4-aminoisoxazole and tetrahydro-2H-pyran-4-one in 5 steps. All the exemplar compds. were evaluated for their GSK3 inhibitory activity in GSK3 inhibition assays with typical Ki values ranging from 0.001 to 10,000 nM. For instance, II exhibited a Ki value of 7 nM. As inhibitors of GSK3, I should prove useful in treatment and prevention of GSK3 assocd. diseases including Alzheimer's disease. [on SciFinder(R)]

  • 8.
    Fang, Xiaotian T.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eriksson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform. PET Centre, Uppsala University Hospital, 751 85 Uppsala, Sweden.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform. Uppsala University Hospital, 751 85 Uppsala, SwedenUppsala University Hospital, 751 85 Uppsala, Sweden.
    Yngve, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform. Uppsala University Hospital, 751 85 Uppsala, SwedenUppsala University Hospital, 751 85 Uppsala, Sweden.
    Cato, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Syvänen, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [(11)C]ABP688 PET imaging and ex vivo immunoblotting2017In: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 113, no Pt A, p. 293-300, article id S0028-3908(16)30459-2Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) into insoluble plaques. Intermediates, Aβ oligomers (Aβo), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [(11)C]PIB, binds and visualizes Aβ plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. Aβo alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning. In order to convey these neurotoxic effects, Aβo requires interaction with the metabotropic glutamate 5 receptor (mGluR5). The aim was to investigate in vivo mGluR5 changes in an Aβ pathology model using PET. Wild type C57/BL6 (wt) and AβPP transgenic mice (tg-ArcSwe), 4, 8, and 16 months old, were PET scanned with [(11)C]ABP688, which is highly specific to mGluR5, to investigate changes in mGluR5. Mouse brains were extracted postscan and mGluR5 and Aβ protofibril levels were assessed with immunoblotting and ELISA respectively. Receptor-dense brain regions (hippocampus, thalamus, and striatum) displayed higher [(11)C]ABP688 concentrations corresponding to mGluR5 expression pattern. Mice had similar uptake levels of [(11)C]ABP688 regardless of genotype or age. Immunoblotting revealed general decline in mGluR5 expression and elevated levels of mGluR5 in 16 months old tg-ArcSwe compared with wt mice. [(11)C]ABP688 could visualize mGluR5 in the mouse brain. In conclusion, mGluR5 levels were found to decrease with age and tended to be higher in tg-ArcSwe compared with wt mice, however these changes could not be quantified with PET.

  • 9. Forngren, B H
    et al.
    Yngve, U
    Forngren, T
    Langstrom, B
    Determination of specific radioactivity for Br-76-labeled compounds measuring the ratio between Br-76 and Br-79 using packed capillary liquid chromatography mass spectrometry2000In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 27, no 8, p. 851-853Article in journal (Refereed)
    Abstract [en]

    Packed capillary liquid chromatography with electrospray mass spectrometry was used for direct determination of the specific radioactivity by calculation of isotope ratios between the Br-76- and Br-76-labeled analogues of N-((3 aminomethyl)benzyl) 4-bromobenzamide. Using 20 muL injections on packed capillary columns, sufficient mass sensitivity was attained for the determination on an injected amount of radioactivity corresponding to approximately 2 MBq (0.3 pmol of the Br-76 isotopic analogue). NUCL MED BIOL 27;6:851-853, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.

  • 10. Gybaeck, Helena
    et al.
    Haeberlein, Markus
    Jonasson, Catrin
    Kihlstroem, Jacob
    Molin, Haakan
    Plobeck, Niklas
    Svensson, Andreas
    Viklund, Jenny
    Yngve, Ulrika.
    Benzoic acid derivatives as glycine receptor inhibitors, their preparation, pharmaceutical compositions, and use in therapy.2006Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The invention relates to benzoic acid derivs. of formula I, which are inhibitors of glycine receptors (GlyRs). In compds. I, Y is H, OH, halo, (un)substituted C1-6 alkoxy, or (un)substituted C1-6 alkyl; R1 is (un)substituted C3-6 cycloalkyl, (un)substituted heterocyclyl, (un)substituted aryl, (un)substituted alkylaryl, (un)substituted heteroaryl, or (un)substituted C3-6 alkyl; L is selected from a bond, heteroarylene, -C(O)-, -CH2-, -CH(OR4)-, -N(OH)-, -N(R4)-, -S(O)n-, where R4 is H or C1-6 alkyl and n is 0, 1, or 2; R2 is H, halo, cyano, dimethylamino, (un)substituted C1-6 alkyl, (un)substituted C3-6 cycloalkyl, (un)substituted heterocyclyl, (un)substituted aryl, (un)substituted alkylaryl, (un)substituted heterocyclyl or (un)substituted heteroaryl; and R3 is OH or C1-6 alkoxy; with the exclusion of several compds. The invention also relates to the prepn. of I, pharmaceutical compns. comprising a therapeutically effective amt. of a compd. I with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers, as well as to the use of the compns. for the treatment of conditions that respond to glycine receptor inhibition, such as neuropathic or inflammatory pain syndromes. Chlorination of 4-methoxybenzenethiol followed by C-substitution with 3-tert-butyl-2-hydroxy-6-methylbenzoic acid and oxidn. gave (arylsulfonyl)benzoic acid II. Several compds. of the invention expressed IC50 values against human GlyR α1 of about 10 nM to about 30 μM (no specific data). [on SciFinder(R)]

  • 11.
    Ladds, Marcus J. G. W.
    et al.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SciLifeLab, Tomtebodavagen 23, SE-17121 Stockholm, Sweden..
    van Leeuwen, Ingeborg M. M.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Drummond, Catherine J.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Chu, Su
    Comprehens Canc Ctr, Div Hematol & Oncol, 1720 2nd Ave South,NP2540, Birmingham, AL 35294 USA..
    Healy, Alan R.
    Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.;Univ St Andrews, Biomed Sci Res Complex, St Andrews KY16 9ST, Fife, Scotland.;EaStCHEM, St Andrews KY16 9ST, Fife, Scotland..
    Popova, Gergana
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Fernandez, Andres Pastor
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Mollick, Tanzina
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SciLifeLab, Tomtebodavagen 23, SE-17121 Stockholm, Sweden..
    Darekar, Suhas
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SciLifeLab, Tomtebodavagen 23, SE-17121 Stockholm, Sweden..
    Sedimbi, Saikiran K.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Nekulova, Marta
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden.;Masaryk Mem Canc Inst, RECAMO, Zluty Kopec 7, Brno 65653, Czech Republic..
    Sachweh, Marijke C. C.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Campbell, Johanna
    Univ Dundee, Ctr Oncol & Mol Med, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Tayside, Scotland..
    Higgins, Maureen
    Univ Dundee, Ctr Oncol & Mol Med, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Tayside, Scotland..
    Tuck, Chloe
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Popa, Mihaela
    Univ Bergen, Dept Clin Sci, Hematol Sect, Ctr Canc Biomarkers,CCBIO, N-5021 Bergen, Norway..
    Safont, Mireia Mayoral
    Univ Bergen, Dept Clin Sci, Hematol Sect, Ctr Canc Biomarkers,CCBIO, N-5021 Bergen, Norway..
    Gelebart, Pascal
    Univ Bergen, Dept Clin Sci, Hematol Sect, Ctr Canc Biomarkers,CCBIO, N-5021 Bergen, Norway..
    Fandalyuk, Zinayida
    Univ Bergen, Dept Clin Sci, Hematol Sect, Ctr Canc Biomarkers,CCBIO, N-5021 Bergen, Norway..
    Thompson, Alastair M.
    Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, Holcombe Blvd, Houston, TX 77030 USA..
    Svensson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gustavsson, Anna-Lena
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Chem Biol Consortium Sweden,Sci Life Lab, SE-17121 Stockholm, Sweden..
    Johansson, Lars
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Chem Biol Consortium Sweden,Sci Life Lab, SE-17121 Stockholm, Sweden..
    Farnegardh, Katarina
    Sci Life Lab, Drug Discovery & Dev Platform, Tomtebodavagen 23, SE-17121 Solna, Sweden..
    Yngve, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Saleh, Aljona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Haraldsson, Martin
    Sci Life Lab, Drug Discovery & Dev Platform, Tomtebodavagen 23, SE-17121 Solna, Sweden..
    D'Hollander, Agathe C. A.
    Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.;Univ St Andrews, Biomed Sci Res Complex, St Andrews KY16 9ST, Fife, Scotland.;EaStCHEM, St Andrews KY16 9ST, Fife, Scotland..
    Franco, Marcela
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Zhao, Yan
    Newcastle Univ, Northern Inst Canc Res, Newcastle Canc Ctr, Newcastle NE1 7RU, England..
    Hakansson, Maria
    SARomics Biostruct, Medicon Village, SE-22381 Lund, Sweden..
    Walse, Bjorn
    SARomics Biostruct, Medicon Village, SE-22381 Lund, Sweden..
    Larsson, Karin
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Peat, Emma M.
    Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland..
    Pelechano, Vicent
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SciLifeLab, Tomtebodavagen 23, SE-17121 Stockholm, Sweden..
    Lunec, John
    Newcastle Univ, Northern Inst Canc Res, Newcastle Canc Ctr, Newcastle NE1 7RU, England..
    Vojtesek, Borivoj
    Masaryk Mem Canc Inst, RECAMO, Zluty Kopec 7, Brno 65653, Czech Republic..
    Carmena, Mar
    Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland..
    Earnshaw, William C.
    Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland..
    McCarthy, Anna R.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Westwood, Nicholas J.
    Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland.;Univ St Andrews, Biomed Sci Res Complex, St Andrews KY16 9ST, Fife, Scotland.;EaStCHEM, St Andrews KY16 9ST, Fife, Scotland..
    Arsenian-Henriksson, Marie
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden..
    Lane, David P.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SciLifeLab, Tomtebodavagen 23, SE-17121 Stockholm, Sweden..
    Bhatia, Ravi
    Comprehens Canc Ctr, Div Hematol & Oncol, 1720 2nd Ave South,NP2540, Birmingham, AL 35294 USA..
    McCormack, Emmet
    Univ Bergen, Dept Clin Sci, Hematol Sect, Ctr Canc Biomarkers,CCBIO, N-5021 Bergen, Norway.;Haukeland Hosp, Haematol Sect, Dept Med, Bergen, Norway..
    Lain, Sonia
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SE-17177 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, SciLifeLab, Tomtebodavagen 23, SE-17121 Stockholm, Sweden..
    A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage2018In: Nature Communications, E-ISSN 2041-1723, Vol. 9, article id 1107Article in journal (Refereed)
    Abstract [en]

    The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.

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  • 12. Langstrom, B
    et al.
    Kihlberg, T
    Bergstrom, M
    Antoni, G
    Bjorkman, M
    Forngren, B H
    Forngren, T
    Hartvig, P
    Markides, K
    Yngve, U
    Ogren, M
    Compounds labelled with short-lived beta(+)-emitting radionuclides and some applications in life sciences. The importance of time as a parameter1999In: Acta Chemica Scandinavica, ISSN 0904-213X, E-ISSN 1902-3103, Vol. 53, no 9, p. 651-669Article in journal (Refereed)
    Abstract [en]

    Some examples of recent development of the synthesis of compounds labelled with short-lived beta(+)-emitting radionuclides will be discussed with an emphasis on the importance of time in selecting a synthetic strategy. Furthermore the use of such labelled compounds to monitor certain processes in areas within the held of analytical chemistry and in various applications in drug development will be presented.

  • 13. Macsari, Istvan
    et al.
    Besidski, Yeygeni
    Csjernyik, Gabor
    Nilsson, Linda I.
    Sandberg, Lars
    Yngve, Ulrika
    Ahlin, Kristofer
    Bueters, Tjerk
    Eriksson, Anders B.
    Lund, Per-Eric
    Venyike, Elisabet
    Oerther, Sandra
    Blakeman, Karin Hygge
    Luo, Lei
    Arvidsson, Per I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat Pain Models2012In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, no 15, p. 6866-6880Article in journal (Refereed)
    Abstract [en]

    The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.

  • 14.
    Nordeman, Patrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Yngve, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wilking, Helena
    Gustavsson, Sven Åke
    Eriksson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Automated GMP-production of α-[11 C]methyl-L-tryptophan using a tracer production system (TPS)2018In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 61, no 14, p. 1106-1109Article in journal (Refereed)
    Abstract [en]

    The radiosynthesis and GMP validation of [11 C]AMT for human use are described. Three consecutive batches were produced giving 940-3790 MBq (4%-17% RCY, decay corrected, based on [11 C]CO2 ) of the tracer. The molar activity at the end of synthesis was 19 to 35 GBq/μmol, the radiochemical purity was ≥98%, and the enantiomeric purity was >99%. While the synthesis method was automated using a new generation of synthesis equipment, tracer production system developed in house, the method should be readily applicable to other synthesis platforms with minor modifications.

  • 15. Nordvall, Gunnar
    et al.
    Yngve, Ulrika.
    Preparation of piperazinyl quinazolines as 5-HT6 modulators.2007Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. represented by the formula I [wherein Q = (hetero)arylalkyl, (hetero)cycloalkylalkyl or alkyl; B = CH or N; R1 = H, OH, halo, alkyl, etc.; R2 = H, (halo)alkyl, aminocarbonylalkyl, etc.; R3 = H, (halo)alkyl or alkylaryl; R4 = CN, halo, alkoxy, etc.; m = 0-2; n = 0-4; and pharmaceutically acceptable salts, solvates or solvated salts thereof] were prepd. as 5-HT6 modulators. For example, reaction of 2,4-dichloroquinazoline with benzenesulfonamide and followed by reaction with N-methylpiperazine, gave N-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]benzenesulfonamide in 6% yield. The radioligand binding assay showed II having Ki of 1.4 nM. Thus, I and their pharmaceutical compns. are useful for the treatment of 5-HT6 mediated disorders, such as Alzheimer's disease, schizophrenia, obesity or Parkinson's disease. [on SciFinder(R)]

  • 16. Nordvall, Gunnar
    et al.
    Yngve, Ulrika.
    Preparation of piperazinyl quinazolines as 5-HT6 modulators.2007Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. represented by the formula I [wherein Q = (hetero)arylalkyl; R1 = OH, halo, alkyl, etc.; R2, R3 = independently H, (halo)alkyl, aminocarbonylalkyl, etc.; n = 0-3; and pharmaceutically acceptable salts, solvates or solvated salts thereof] were prepd. as 5-HT6 modulators. For example, reaction of 2-chloro-4-(4-methylpiperazin-1-yl)quinazoline with N-methyl-4-chlorobenzenesulfonamide gave II in 10% yield. The radioligand binding assay showed II having Ki of 200 nM. Thus, I and their pharmaceutical compns. are useful for the treatment of 5-HT6 mediated disorders, such as Alzheimer's disease, schizophrenia, obesity or Parkinson's disease. [on SciFinder(R)]

  • 17.
    Popova, Gergana
    et al.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17165 Stockholm, Sweden..
    Ladds, Marcus J. G. W.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17165 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SciLifeLab, SE-17165 Stockholm, Sweden..
    Johansson, Lars
    Karolinska Inst, Dept Med Biochem & Biophys, SciLifeLab, Chem Biol Consortium Sweden, SE-17121 Stockholm, Sweden..
    Saleh, Aljona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab. Drug Discovery & Dev Platform,ADME Therapeut Faci, SE-75123 Uppsala, Sweden..
    Larsson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Drug Discovery & Dev Platform, SE-75123 Uppsala, Sweden..
    Sandberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Drug Discovery & Dev Platform, SE-75123 Uppsala, Sweden.;Stockholm Univ, Dept Organ Chem, SciLifeLab, Drug Discovery & Dev Platform, SE-17121 Stockholm, Sweden..
    Sahlberg, Sara Haggblad
    Stockholm Univ, Dept Biochem & Biophys, SciLifeLab, Drug Discovery & Dev Platform, SE-17121 Stockholm, Sweden..
    Qian, Weixing
    Umea Univ, Labs Chem Biol Umea, Chem Biol Consortium Sweden, SE-90187 Umea, Sweden..
    Gullberg, Hjalmar
    Stockholm Univ, Dept Biochem & Biophys, SciLifeLab, Drug Discovery & Dev Platform, SE-17121 Stockholm, Sweden..
    Garg, Neeraj
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Chemical Biology for Biomarker Discovery. Drug Discovery & Dev Platform, SE-75123 Uppsala, Sweden..
    Gustavsson, Anna-Lena
    Karolinska Inst, Dept Med Biochem & Biophys, SciLifeLab, Chem Biol Consortium Sweden, SE-17121 Stockholm, Sweden..
    Haraldsson, Martin
    Karolinska Inst, Dept Med Biochem & Biophys, SciLifeLab, Chem Biol Consortium Sweden, SE-17121 Stockholm, Sweden..
    Lane, David
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17165 Stockholm, Sweden..
    Yngve, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Drug Discovery & Dev Platform, SE-75123 Uppsala, Sweden..
    Lain, Sonia
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17165 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SciLifeLab, SE-17165 Stockholm, Sweden..
    Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability2020In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 63, no 8, p. 3915-3934Article in journal (Refereed)
    Abstract [en]

    Human dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pyrimidine synthesis pathway, is a target for the treatment of rheumatoid arthritis and multiple sclerosis and is re-emerging as an attractive target for cancer therapy. Here we describe the optimization of recently identified tetrahydroindazoles (HZ) as DHODH inhibitors. Several of the HZ analogues synthesized in this study are highly potent inhibitors of DHODH in an enzymatic assay, while also inhibiting cancer cell growth and viability and activating p53-dependent transcription factor activity in a reporter cell assay. Furthermore, we demonstrate the specificity of the compounds toward the de novo pyrimidine synthesis pathway through supplementation with an excess of uridine. We also show that induction of the DNA damage marker gamma-H2AX after DHODH inhibition is preventable by cotreatment with the pancaspase inhibitor Z-VAD-FMK. Additional solubility and in vitro m etabolic stability profiling revealed compound 51 as a favorable candidate for preclinical efficacy studies.

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  • 18. Stroem, Peter
    et al.
    Malmquist, Jonas
    Hansson, Jonas
    Yngve, Ulrika
    Claesson, Alf.
    Tritium labeling of a class of spirooxazaindolamines possessing analgesic properties.2004In: Synth. Appl. Isot. Labelled Compd., Proc. Int. Symp., 8th, 2004, p. 285-288Conference paper (Refereed)
    Abstract [en]

    In order to study the mol. action of a class of spirooxazaindolamines with promising analgesic activity, tritiated material was prepd. Efficient synthesis of 3H-labeled material allowed essential information on the mol. mechanism for this class of compds. to be obtained. Different approaches for the introduction of the 3H-label on the spirooxazaindole skeleton via 3H-methyliodide were evaluated involving lithium-mediated coupling, zinc-mediated coupling and Stille coupling. Tritiation using 3H2 (g) with a Pd-catalyst was also tested. [on SciFinder(R)]

  • 19.
    Velikyan, Irina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Lendvai, Gabor
    Välilä, Maria
    Roivainen, Anne
    Yngve, Ulrika
    Bergström, Mats
    Långström, Bengt
    Microwave accelerated 68Ga-labelling of oligonucleotides2004In: Journal of Labelled Compounds & Radiopharmaceuticals, Vol. 47, p. 79-89Article in journal (Refereed)
  • 20. Wensbo, David
    et al.
    Xin, Tao
    Stefanac, Tomislav
    Arora, Jalaj
    Edwards, Louise
    Isaac, Methvin
    Slassi, Abdelmalik
    Stormann, Thomas M.
    McLeod, Donald A.
    Kers, Annika
    Malmberg, Johan
    Oscarsson, Karin
    Gyback, Helena
    Johansson, Martin
    Minidis, Alexander
    Waldman, Mangus
    Yngve, Ulrika
    Osterwall, Christoffer.
    Preparation of five-membered heterocyclic compounds as mGluR5 receptor antagonists.2004Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The present invention relates to five-membered heterocyclic compds. (shown as I; variables defined below; e.g. II), a process for their prepn. and new intermediates prepd. therein, pharmaceutical formulations contg. said compds. and to the use of said compds. in therapy, e.g. neurol., psychiatric and chronic and acute pain disorders (no data). Typical IC50 values for mGluR5 receptor antagonist activity are ≤10 μM; no values for individual compds. are given. Methods of prepn. are claimed and example prepns. and/or characterization data are included for ∼800 examples of I and intermediates. For example, [3-[3-[[[4-methyl-5-(thiophen-2-yl)-4H-[1,2,4]triazol-3-yl]sulfanyl]methyl][1,2,4]oxadiazol-5-yl]phenyl]carbamic acid tert-Bu ester was prepd. in 79% yield by condensation of 4-methyl-5-(thiophen-2-yl)-4H-[1,2,4]triazole-3-thiol with [3-(3-chloromethyl-[1,2,4]oxadiazol-5-yl)phenyl]carbamic acid tert-Bu ester in MeCN in the presence of K2CO3. For I: P = H, C3-7alkyl or a 3- to 8-membered ring contg. ≥1 atoms = C, N, O and S, which ring may optionally be fused with a 5- or 6-membered ring contg. ≥1 C, N, O and S; R1 = H, hydroxy, halo, nitro, C1-6-alkylhalo, OC1-6alkylhalo, C1-6alkyl, OC1-6alkyl, C2-6alkenyl, OC2-6alkenyl, C2-6alkynyl, OC2-6alkynyl, C0-6alkylC3-6cycloalkyl, etc. and a 5- or 6-membered ring contg. ≥1 C, N, O and S, wherein said ring may be substituted by ≥1 A. M1 = a bond, C1-3alkyl, C2-3alkenyl, C2-3alkynyl, C0-4alkyl(CO)C0-4alkyl, C0-3alkylOC0-3alkyl, C0-3alkyl(CO)NR5, C0-3alkyl(CO)NR5C0-3alkyl, C0-4-alkylNR5, C0-3alkylSC0-3alkyl, etc.; R2 = H, hydroxy, C0-6alkylcyano, oxo, NR5, NOR5, C1-4alkylhalo, halo, C1-4alkyl, etc. X1, X2 and X3 = CR, CO, N, NR, O and S; R = H, C0-3alkyl, halo, C0-3alkylOR5, C0-3-alkylNR5R6, C0-3alkyl(CO)OR5, C0-3alkylNR5R6 and C0-3alkylaryl; M2 = a bond, C1-3alkyl, C3-7cycloalkyl, C2-3alkenyl, C2-3alkynyl, C0-4alkyl(CO)C0-4alkyl, C0-3alkylOC0-3alkyl, etc.; R3 = H, hydroxy, C0-6alkylcyano, oxo, NR, NOR5, C1-4alkylhalo, halo, C1-4alkyl, etc. X4 = C0-4alkylR5, C0-4alkyl(NR5R6), C0-4-alkyl(NR5R6):N, NR5C0-4alkyl(NR5R6):N, NOC0-4alkyl, C1-4alkylhalo, C, O, SO, SO2 and S; Q is a 5- or 6-membered ring contg. ≥1 C, N, O and S, which group may optionally be fused with a 5- or 6-membered ring contg. ≥1 C, N, O and S and which fused ring may be substituted by ≥1 A. R4 = H, hydroxy, C0-6alkylcyano, oxo, NR5, NOR5, C1-4alkylhalo, halo, C1-4alkyl, OC1-4alkyl, OC0-6alkylaryl, etc. and a 5- or 6-membered ring contg. ≥1 atoms = C, N, O or S, wherein said ring may be substituted by ≥1 A; R5, R6 = H, OH, C1-6alkyl, etc.; A = H, OH, O, halo, nitro, C0-6alkylcyano, etc.; m = 0-4; and n = 0-3; addnl. details are given in the claims. [on SciFinder(R)]

  • 21. Wu, F
    et al.
    Lendvai, G
    Yngve, U
    Eriksson, B
    Langstrom, B
    Bergstrom, M
    Hybridisation of [Br-76]-labelled antisense oligonucleotides to Chromogranin A mRNA verified by RT-PCR2004In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 31, no 8, p. 1073-1078Article in journal (Refereed)
    Abstract [en]

    Methods have been developed to label oligonucleotides (ODNs) in the 5'-position with Br-76 via a prosthetic group on a hexylamino-linker. The purpose of the study was to explore whether the labelling procedure would prevent specific hybridisation by using reverse transcription-polymerase chain reaction (RT-PCR) followed by sequencing of the PCR product. Antisense ODNs (30 mer, specific for rat Chromogranin A [CgA] mRNA) with phosphodiester (O-ODN) or phosphothiciate (S-ODN) backbone, either unlabelled or labelled with Br-76, served as one of the primers in individual PCR reactions. Using O-ODN as a primer, irrespective of being labelled or not, a selected 225-bp PCR fragment was successfully amplified. However, no amplification was obtained using S-ODN as a primer. The proper PCR products were only detected in the sample prepared from the adrenal gland, but not in that from the heart, liver or kidney. Autoradiographic recording of the gel, after gel electrophoresis, revealed radioactive signals corresponding to the amplified PCR products. The sequence of the PCR product matched the rat CgA mRNA sequence obtained from the EMBL database. RT-PCR is an attractive method to identify the selective binding of modified ODNs to target mRNA. This method confirmed that the labelling with Br-76 did not change the hybridisation ability of antisense O-ODN. (C) 2004 Elsevier Inc. All rights reserved.

  • 22. Wu, F
    et al.
    Yngve, U
    Hedberg, E
    Honda, M
    Lu, L
    Eriksson, B
    Watanabe, Y
    Bergstrom, M
    Langstrom, B
    Distribution of Br-76-labeled antisense oligonucleotides of different length determined ex vivo in rats2000In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 10, no 3, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Oligonucleotides may hybridize with high selectivity to an RNA sequence and can be used for the monitoring of gene expression or for its inhibition in experimental or therapeutic purposes. As part of the development of positron emission tomography (PET) methods, different lengths (30, 20, 12 and 6 mer) of antisense phosphorothioate oligonucleotides complementary to rat chromogranin A were labeled with [Br-76] using a prosthetic group. The Br-76-oligonucleotides were injected into rat's tail vein (1-2 MBq/rat), and the radioactivity distribution was analyzed after 20 h using whole body autoradiography or by measurement of organ radioactivity concentration. The whole body autoradiography showed different distribution depending on the oligonucleotide length. The organs with highest uptake changed from kidney cortex (with 6 or 12 mer), kidney cortex and liver (with 20 mer), to liver and spleen (with 30 mer). With 20 or 30 mer sequences, uptake could be observed in the adrenals. Kidneys and livers from rats receiving 20 mer or 30 mer Br-76-oligonucleotides were analyzed with respect to subcellular distribution and DNA/RNA/protein fraction. 30%-45% of the radioactivity was found in the nuclear fraction. More than 80% of the radioactivity was recovered in the high molecular weight fraction (as proteins or oligonucleotides longer than 10 mer) using size exclusion (NAP 5) gelfiltration or cetylpyridinium bromide (CPB) precipitation. This work indicates the potential to perform kinetic whole body studies of Br-76-oligonucleotides using PET. (C) 2000 Elsevier Science B.V. All rights reserved.

  • 23. Yngve, U.
    et al.
    Hedberg, E.
    Tolmachev, V.
    Langstrom, B.
    Synthesis of N-succinimidyl-4-[76Br]bromobenzoate and its use in labeling of amino-containing macromolecules.1998In: Synth. Appl. Isot. Labelled Compd. 1997, Proc. Int. Symp., 6th, 1998, p. 303-305Conference paper (Refereed)
    Abstract [en]

    N-succinimidyl-4-[76Br]bromobenzoate was prepd. and incorporated as labeling agent into DNA and bovine serum albumin and chromogranin. [on SciFinder(R)]

  • 24. Yngve, Ulrika
    et al.
    Hedberg, Elisabeth
    Lövqvist, Anna
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Långström, Bengt
    Synthesis of N-Succinimidyl 4-[76Br]Bromobenzoate and its Use in Conjugation Labelling of Macromolecules1999In: Acta Chemica Scandinavica, ISSN 0904-213X, E-ISSN 1902-3103, Vol. 53, p. 508-512Article in journal (Refereed)
  • 25.
    Yngve, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Långstrom, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Labelling of octreotide using Br-76-prosthetic groups2001In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 44, no 8, p. 561-573Article in journal (Refereed)
    Abstract [en]

    A method for labelling the octapeptide octreotide (D-Phe-Cys-Phe-D-TrpLys-Thr-Cys-Thr(ol)) with the positron emitting Br-76 (T-1/2 = 16 h) is presented. epsilon -Boc-protected octreotide was conjugated to N-succinimidyl 4-[Br-76]bromobenzoate 1 and N-succinimidyl 5-[Br-76]bromo-3-pyridinecarboxylate 3 using microwave heating. The conjugates 4 and 5 were isolated in 50-55% radiochemical yield after the removal of the protecting Boc-group. Compound 3 was synthesised from the corresponding trimethylstannyl-precursor in 25% radiochemical yield. The synthesis of methyl-4-[Br-76] bromobenzimidate 8 in 40% radiochemical yield from the precursor methyl -4-trimethylstannylbenzimidate is also described. Experiments were performed to react 8 with Boc-octreotide but no product was obtained. The binding-properties of Br-76-conjugates 4 and 5 to meningiomas were investigated using frozen section autoradiography. Compound 5 showed better binding properties than 4.

  • 26.
    Yngve, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Nordeman, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Auberson, Yves
    Novartis Inst BioMed Res, Basel, Switzerland..
    Machauer, Rainer
    Novartis Inst BioMed Res, Basel, Switzerland..
    Briard, Emmanuelle
    Novartis Inst BioMed Res, Basel, Switzerland..
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Tracing BACE: Synthesis and evaluation of beta-secretase inhibitors as ligands for PET imaging2015In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 58, p. S51-S51Article in journal (Other academic)
  • 27. Yngve, Ulrika
    et al.
    Paulsen, Kim
    Macsari, Istvan
    Sundstrom, Marie
    Santangelo, Ellen
    Linde, Christian
    Bogar, Krisztian
    Lake, Fredrik
    Besidski, Yevgeni
    Malmborg, Jonas
    Stromberg, Kia
    Appelkvist, Paulina
    Radesater, Ann-Cathrine
    Olsson, Fredrik
    Bergstrom, Daniel
    Klintenberg, Rebecka
    Arvidsson, Per I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Triazolopyrimidinones as gamma-secretase modulators: structure-activity relationship, modulator profile, and in vivo profiling2013In: MedChemComm, ISSN 2040-2503, E-ISSN 2040-2511, Vol. 4, no 2, p. 422-431Article in journal (Refereed)
    Abstract [en]

    The structure-activity relationship for a series of potent g-secretase modulators based on the 6,7-dihydro4H-[1,2,4]triazolo[1,5-a]pyrimidin-5-one scaffold is described. Furthermore, we report details regarding the modulator profile on A beta processing, as well as in vivo efficacy, for the optimized compounds.

  • 28. Yngve, Ulrika
    et al.
    Söderman, Peter
    Svensson, Mats
    Rosqvist, Susanne
    Arvidsson, Per I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Imidazopyridine-based inhibitors of glycogen synthase kinase 3: synthesis and evaluation of amide isostere replacements of the carboxamide scaffold2012In: Chemistry and Biodiversity, ISSN 1612-1872, E-ISSN 1612-1880, Vol. 9, no 11, p. 2442-2452Article in journal (Refereed)
    Abstract [en]

    In this study, we explored the effect of bioisostere replacement in a series of glycogen synthase kinase 3 (GSK3) inhibitors based on the imidazopyridine core. The synthesis and biological evaluation of a number of novel sulfonamide, 1,2,4-oxadiazole, and thiazole derivates as amide bioisosteres, as well as a computational rationalization of the obtained results are reported.

1 - 28 of 28
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