LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: Design and Synthesis of Pyrrolo[2,3-

    Williamson, Douglas S / Smith, Garrick P / Mikkelsen, Gitte K / Jensen, Thomas / Acheson-Dossang, Pamela / Badolo, Lassina / Bedford, Simon T / Chell, Victoria / Chen, I-Jen / Dokurno, Pawel / Hentzer, Morten / Newland, Samantha / Ray, Stuart C / Shaw, Terry / Surgenor, Allan E / Terry, Lindsey / Wang, Yikang / Christensen, Kenneth V

    Journal of medicinal chemistry

    2021  Volume 64, Issue 14, Page(s) 10312–10332

    Abstract: Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson's disease treatment. Fragment hit-derived pyrrolo[2,3- ...

    Abstract Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson's disease treatment. Fragment hit-derived pyrrolo[2,3-
    MeSH term(s) Checkpoint Kinase 1/chemistry ; Checkpoint Kinase 1/metabolism ; Crystallography, X-Ray ; Dose-Response Relationship, Drug ; Drug Design ; HEK293 Cells ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/antagonists & inhibitors ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism ; Models, Molecular ; Molecular Structure ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Pyrimidines/chemical synthesis ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Pyrroles/chemical synthesis ; Pyrroles/chemistry ; Pyrroles/pharmacology ; Structure-Activity Relationship
    Chemical Substances Protein Kinase Inhibitors ; Pyrimidines ; Pyrroles ; Pyrrolo(2,3-d)pyrimidine ; CHEK1 protein, human (EC 2.7.11.1) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; LRRK2 protein, human (EC 2.7.11.1) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1)
    Language English
    Publishing date 2021-06-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.1c00720
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential.

    Sams, Anette G / Hentzer, Morten / Mikkelsen, Gitte K / Larsen, Krestian / Bundgaard, Christoffer / Plath, Niels / Christoffersen, Claus T / Bang-Andersen, Benny

    Journal of medicinal chemistry

    2010  Volume 53, Issue 17, Page(s) 6386–6397

    Abstract: The discovery and structure-activity relationship (SAR) of a series of allosteric muscarinic M(1) receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an ... ...

    Abstract The discovery and structure-activity relationship (SAR) of a series of allosteric muscarinic M(1) receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M(1) receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.
    MeSH term(s) Allosteric Regulation ; Animals ; Benzeneacetamides/chemical synthesis ; Benzeneacetamides/pharmacokinetics ; Benzeneacetamides/pharmacology ; Benzoxazines/chemical synthesis ; Benzoxazines/pharmacokinetics ; Benzoxazines/pharmacology ; Brain/metabolism ; Calcium/metabolism ; Cell Line ; Cricetinae ; Cricetulus ; Female ; Hepatocytes/metabolism ; Humans ; In Vitro Techniques ; Male ; Maze Learning/drug effects ; Memory, Short-Term/drug effects ; Mice ; Nootropic Agents/chemical synthesis ; Nootropic Agents/pharmacokinetics ; Nootropic Agents/pharmacology ; Oxazines/chemical synthesis ; Oxazines/pharmacokinetics ; Oxazines/pharmacology ; Piperidines/chemical synthesis ; Piperidines/pharmacokinetics ; Piperidines/pharmacology ; Radioligand Assay ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M1/agonists ; Structure-Activity Relationship
    Chemical Substances Benzeneacetamides ; Benzoxazines ; N-(1-(3-(3-oxo-2,3-dihydrobenzo(1,4)oxazin-4-yl)propyl)piperidin-4-yl)-2-phenylacetamide ; Nootropic Agents ; Oxazines ; Piperidines ; Receptor, Muscarinic M1 ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2010-09-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm100697g
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} ester (Lu AA47070): a phosphonooxymethylene prodrug of a potent and selective hA(2A) receptor antagonist.

    Sams, Anette G / Mikkelsen, Gitte K / Larsen, Mogens / Langgård, Morten / Howells, Mark E / Schrøder, Tenna J / Brennum, Lise T / Torup, Lars / Jørgensen, Erling B / Bundgaard, Christoffer / Kreilgård, Mads / Bang-Andersen, Benny

    Journal of medicinal chemistry

    2011  Volume 54, Issue 3, Page(s) 751–764

    Abstract: The discovery and structure-activity relationship of a series of hA(2A) receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's ... ...

    Abstract The discovery and structure-activity relationship of a series of hA(2A) receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptable ADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.
    MeSH term(s) Adenosine A2 Receptor Antagonists/chemical synthesis ; Adenosine A2 Receptor Antagonists/pharmacokinetics ; Adenosine A2 Receptor Antagonists/pharmacology ; Animals ; Antiparkinson Agents/chemical synthesis ; Antiparkinson Agents/pharmacokinetics ; Antiparkinson Agents/pharmacology ; CHO Cells ; Caco-2 Cells ; Cell Membrane Permeability ; Cricetinae ; Cricetulus ; Crystallography, X-Ray ; High-Throughput Screening Assays ; Humans ; Male ; Mice ; Models, Molecular ; Organophosphates/chemical synthesis ; Organophosphates/pharmacokinetics ; Organophosphates/pharmacology ; Prodrugs/chemical synthesis ; Prodrugs/pharmacokinetics ; Prodrugs/pharmacology ; Radioligand Assay ; Rats ; Rats, Sprague-Dawley ; Solubility ; Stereoisomerism ; Structure-Activity Relationship ; Thiazoles/chemical synthesis ; Thiazoles/pharmacokinetics ; Thiazoles/pharmacology ; Water
    Chemical Substances Adenosine A2 Receptor Antagonists ; Antiparkinson Agents ; Organophosphates ; Prodrugs ; Thiazoles ; phosphoric acid mono-(2-(4-(3,3-dimethylbutyrylamino)-3,5-difluorobenzoylimino)thiazol-3-ylmethyl) ester ; Water (059QF0KO0R)
    Language English
    Publishing date 2011-02-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm1008659
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top