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  1. Book: Inflammatory processes

    Letts, L. Gordon

    molecular mechanisms and therapeutic opportunities

    (Progress in inflammation research)

    2000  

    Institution Inflammation Research Association
    Author's details [In november 1 - 5, 1998 the 9th international conference of the Inflammation Research Association was held ... Hershey, Pennsylvania]. L. Gordon Letts ... (ed.)
    Series title Progress in inflammation research
    Keywords Entzündung
    Subject Inflammatio ; Entzündungsreaktion
    Language English
    Size IX, 144 S.: graph. Darst.
    Publisher Birkhäuser
    Publishing place Basel u.a.
    Publishing country Switzerland
    Document type Book
    HBZ-ID HT012768490
    ISBN 3-7643-6025-9 ; 978-3-7643-6025-2
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2000 A 3323 order for loan Magazin

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  2. Article: Cyclo-oxygenase-2 inhibition and exacerbation of myocardial dysfunction--protection with nitric oxide?

    Letts, Gordon

    British journal of pharmacology

    2002  Volume 135, Issue 6, Page(s) 1345–1346

    MeSH term(s) Animals ; Cardiomyopathies/enzymology ; Cardiomyopathies/physiopathology ; Cardiomyopathies/prevention & control ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/adverse effects ; Cyclooxygenase Inhibitors/pharmacology ; Humans ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/metabolism ; Membrane Proteins ; Nitric Oxide/physiology ; Prostaglandin-Endoperoxide Synthases/metabolism
    Chemical Substances Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Isoenzymes ; Membrane Proteins ; Nitric Oxide (31C4KY9ESH) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
    Language English
    Publishing date 2002-03
    Publishing country England
    Document type Comment ; Journal Article
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1038/sj.bjp.0704584
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Frontiers in nephrology: targeting inflammation using novel nitric oxide donors.

    Letts, Gordon / Loscalzo, Joseph

    Journal of the American Society of Nephrology : JASN

    2007  Volume 18, Issue 11, Page(s) 2863–2869

    Abstract: Chimeric molecules are single-chemical entities that possess at least two separate functions. In the design of new chimeric medicines, the two biologic actions are often designed to be synergistic and, thereby, complement each other in activating a ... ...

    Abstract Chimeric molecules are single-chemical entities that possess at least two separate functions. In the design of new chimeric medicines, the two biologic actions are often designed to be synergistic and, thereby, complement each other in activating a specific target, such as a gene, a receptor, or an enzyme. In most chimeric molecules, one functionality is designed to provide a high affinity to a designated site, thereby permitting the targeting of the second functionality, which is usually nonspecific. This review focuses on the development of two classes of chimeric medicines, anti-inflammatory and diuretic chimeric agents, both of which incorporate a nitric oxide moiety into the parent pharmacophore.
    MeSH term(s) Cyclooxygenase 2 Inhibitors/pharmacology ; Diuretics/pharmacology ; Drug Synergism ; Humans ; Inflammation/drug therapy ; Nitric Oxide Donors/therapeutic use ; Nitric Oxide Synthase Type II/drug effects
    Chemical Substances Cyclooxygenase 2 Inhibitors ; Diuretics ; Nitric Oxide Donors ; NOS2 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type II (EC 1.14.13.39)
    Language English
    Publishing date 2007-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2007030321
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book: Chemokine biology

    Moser, Bernhard / Letts, Gordon L / Neote, Kuldeep

    basic research and clinical application

    (Progress in inflammation research)

    2006  

    Series title Progress in inflammation research
    MeSH term(s) Chemokines ; Receptors, Chemokine
    Language English
    Dates of publication 2006-2007
    Size 2 v. :, ill.
    Publisher Birkhäuser Verlag
    Publishing place Basel ; Boston
    Document type Book
    ISBN 9783764368258 ; 376436825X ; 3764374233 ; 9783764371951 ; 3764371951 ; 9783764374372 ; 3764374373 ; 9783764374235
    Database Catalogue of the US National Library of Medicine (NLM)

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  5. Article ; Online: Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers.

    Khanapure, Subhash P / Garvey, David S / Janero, David R / Letts, L Gordon

    Current topics in medicinal chemistry

    2007  Volume 7, Issue 3, Page(s) 311–340

    Abstract: In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid (AA) from membrane phospholipids. The AA is subsequently transformed by cyclooxygenase (COX) and lipoxygenase (LO) ... ...

    Abstract In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid (AA) from membrane phospholipids. The AA is subsequently transformed by cyclooxygenase (COX) and lipoxygenase (LO) pathways to prostaglandins, thromboxane and leukotrienes collectively termed eicosanoids. Eicosanoid production is considerably increased during inflammation. Both COX and LO pathways are of particular clinical relevance. The COX pathway is the major target for non-steroidal anti-inflammatory drugs (NSAIDs), the most popular medications used to treat pain, fever and inflammation. Although their anti-inflammatory effects are well known, their long-term use is associated with gastrointestinal (GI) complications such as ulceration. In 1991, it was discovered that COX exists in two distinct isozymes, COX-1 and COX-2, of which COX-2 is primarily expressed at sites of inflammation and produces pro-inflammatory eicosanoids. For this reason, COX-2 selective inhibitors (COXIBs) have been developed recently as anti-inflammatory agents to minimize the risk of GI toxicity. Recently, some COX-2 selective inhibitors have shown adverse cardiovascular side effects, resulting in the withdrawal of rofecoxib and valdecoxib from the market. Selective inhibition of COX-2 without reducing COX-1-mediated thromboxane production could alter the balance between prostacyclin and thromboxane and promote a prothrombotic state, thereby explaining the observed COX-2 cardiovascular risk. In this review, we describe mechanisms for the production of pro-inflammatory eicosanoid mediators contributing to inflammation and summarize promising options for the prevention of inflammatory mediator formation and the therapeutic inhibition of pain and inflammation.
    MeSH term(s) Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Cyclooxygenase 2 Inhibitors/chemistry ; Cyclooxygenase 2 Inhibitors/pharmacology ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Eicosanoids/biosynthesis ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Lipoxygenase/metabolism ; Prostaglandin-Endoperoxide Synthases/metabolism
    Chemical Substances Anti-Inflammatory Agents ; Cyclooxygenase 2 Inhibitors ; Eicosanoids ; Lipoxygenase (EC 1.13.11.12) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
    Language English
    Publishing date 2007-02-16
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 2064823-6
    ISSN 1873-4294 ; 1568-0266
    ISSN (online) 1873-4294
    ISSN 1568-0266
    DOI 10.2174/156802607779941314
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Conference proceedings: Inflammatory processes

    Letts, L. Gordon / Morgan, Douglas W

    molecular mechanisms and therapeutic opportunities

    (Progress in inflammation research)

    2000  

    Institution Inflammation Research Association. / International Conference
    Author's details L. Gordon Letts, Douglas W. Morgan, editors
    Series title Progress in inflammation research
    MeSH term(s) Inflammation/immunology ; Drug Carriers ; Inflammation/drug therapy ; Signal Transduction
    Language English
    Size ix, 144 p. :, ill.
    Publisher Birkhäuser Verlag
    Publishing place Basel ; Boston
    Document type Book ; Conference proceedings
    ISBN 9783764360252 ; 3764360259
    Database Catalogue of the US National Library of Medicine (NLM)

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  7. Article: Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: nitric oxide-donor naproxen prodrugs.

    Ranatunge, Ramani R / Augustyniak, Michael E / Dhawan, Vijay / Ellis, James L / Garvey, David S / Janero, David R / Letts, L Gordon / Richardson, Stewart K / Shumway, Mathew J / Trocha, A Mark / Young, Delano V / Zemtseva, Irina S

    Bioorganic & medicinal chemistry

    2006  Volume 14, Issue 8, Page(s) 2589–2599

    Abstract: A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, ...

    Abstract A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, 5a, 5b, 7b, and 7c exhibited anti-inflammatory activity equivalent to that of the parent NSAID, naproxen-Na, in the rat carrageenan paw edema model. At equimolar doses relative to naproxen-Na, the NO-donor glycolamide derivatives 4a, 4b, 5a, 5b, 7b, and 7c were gastro-sparing in the rat. Naproxen formation from these NO-donor glycolamides varied among the structures examined, with the N-substituent on the amide group having a particular influence, and demonstrated their prodrug nature. Compound 7b was selected for exemplary demonstration that the glycolamide nitrates can be bioactivated to release NO. These data open the possibility that naproxen glycolamide nitrates may represent a safer alternative to naproxen as anti-inflammatory medicines.
    MeSH term(s) Amides/chemistry ; Animals ; Anti-Inflammatory Agents/chemical synthesis ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Gastritis/chemically induced ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Mass Spectrometry ; Naproxen/chemical synthesis ; Naproxen/chemistry ; Naproxen/pharmacology ; Nitric Oxide Donors/chemical synthesis ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology ; Prodrugs ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Amides ; Anti-Inflammatory Agents ; Nitric Oxide Donors ; Prodrugs ; Naproxen (57Y76R9ATQ)
    Language English
    Publishing date 2006-04-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2005.11.040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: 3-(2-Methoxytetrahydrofuran-2-yl)pyrazoles: a novel class of potent, selective cyclooxygenase-2 (COX-2) inhibitors.

    Ranatunge, Ramani R / Earl, Richard A / Garvey, David S / Janero, David R / Letts, L Gordon / Martino, Allison M / Murty, Madhavi G / Richardson, Stewart K / Schwalb, David J / Young, Delano V / Zemtseva, Irina S

    Bioorganic & medicinal chemistry letters

    2004  Volume 14, Issue 24, Page(s) 6049–6052

    Abstract: A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4-10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4- ... ...

    Abstract A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4-10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4-methanesulfonylphenyl)-3-(2-methoxytetrahydrofuran-2-yl)-1-p-tolyl-1H-pyrazole 5 showed potent and selective COX-2 inhibition (IC50 for COX-1: >100 microM and COX-2: 1.2 microM).
    MeSH term(s) Cyclooxygenase 1 ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/chemical synthesis ; Cyclooxygenase Inhibitors/chemistry ; Cyclooxygenase Inhibitors/pharmacology ; Drug Evaluation, Preclinical ; Humans ; Isoenzymes/antagonists & inhibitors ; Membrane Proteins ; Molecular Structure ; Prostaglandin-Endoperoxide Synthases/blood ; Prostaglandin-Endoperoxide Synthases/drug effects ; Pyrazoles/chemical synthesis ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Structure-Activity Relationship
    Chemical Substances Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Isoenzymes ; Membrane Proteins ; Pyrazoles ; Cyclooxygenase 1 (EC 1.14.99.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS1 protein, human (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
    Language English
    Publishing date 2004-12-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2004.09.073
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Synthesis and selective cyclooxygenase-2 (COX-2) inhibitory activity of a series of novel bicyclic pyrazoles.

    Ranatunge, Ramani R / Garvey, David S / Janero, David R / Letts, L Gordon / Martino, Allison M / Murty, Madhavi G / Richardson, Stewart K / Young, Delano V / Zemetseva, Irina S

    Bioorganic & medicinal chemistry

    2004  Volume 12, Issue 6, Page(s) 1357–1366

    Abstract: Novel series of pyrazolo[5,1-b]1,3-oxazolidines, pyrazolo[5,1-b]1,3-oxazines and imidazolidino[1,2-d]pyrazoles were synthesized. These compounds were evaluated in vitro for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in ...

    Abstract Novel series of pyrazolo[5,1-b]1,3-oxazolidines, pyrazolo[5,1-b]1,3-oxazines and imidazolidino[1,2-d]pyrazoles were synthesized. These compounds were evaluated in vitro for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human whole blood (HWB). Several of the compounds were found to be novel and selective COX-2 inhibitors, the most potent and selective being 1-(5-cyclohexyl (2H,3H-pyrazolo[5,1-b]-1,3-oxazolidin-6-yl)-4-(methylsulfonyl)benzene, 7a (IC(5o) for COX-1>100 microM; for COX-2=1.3 microM).
    MeSH term(s) Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis ; Bridged Bicyclo Compounds, Heterocyclic/chemistry ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/chemical synthesis ; Cyclooxygenase Inhibitors/chemistry ; Cyclooxygenase Inhibitors/pharmacology ; Humans ; Isoenzymes/antagonists & inhibitors ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases ; Pyrazoles/chemical synthesis ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Structure-Activity Relationship
    Chemical Substances Bridged Bicyclo Compounds, Heterocyclic ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Isoenzymes ; Membrane Proteins ; Pyrazoles ; Cyclooxygenase 1 (EC 1.14.99.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS1 protein, human (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
    Language English
    Publishing date 2004-03-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2004.01.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: NMI-1182, a gastro-protective cyclo-oxygenase-inhibiting nitric oxide donor.

    Ellis, James L / Augustyniak, Michael E / Cochran, Edward D / Earl, Richard A / Garvey, David S / Gordon, Laura J / Janero, David R / Khanapure, Subhash P / Letts, L Gordon / Melim, Terry L / Murty, Madhavi G / Schwalb, David J / Shumway, Matthew J / Selig, William M / Trocha, A Mark / Young, Delano V / Zemtseva, Irina S

    Inflammopharmacology

    2005  Volume 12, Issue 5-6, Page(s) 521–534

    Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective ... ...

    Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective we have synthesized a NO-donating prodrug of naproxen named NMI-1182. We evaluated two cyclo-oxygenase (COX)-inhibiting nitric oxide donors (CINODs), NMI-1182 and AZD3582, for their ability to be gastro-protective compared to naproxen and for their anti-inflammatory activity. NMI-1182 and AZD3582 were found to produce similar inhibition of COX activity to that produced by naproxen. Both NMI-1182 and AZD3582 produced significantly less gastric lesions after oral administration than naproxen. All three compounds effectively inhibited paw swelling in the rat carrageenan paw edema model. In the carrageenan air pouch model all three compounds significantly reduced PGE2 levels in the pouch exudate but only NMI-1182 and naproxen inhibited leukocyte influx. These data demonstrate that NMI-1182 has comparable anti-inflammatory activity to naproxen but with a much reduced likelihood to cause gastric damage.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/blood ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/pharmacology ; Aorta, Abdominal/drug effects ; Aorta, Abdominal/physiology ; Carrageenan ; Cyclooxygenase 1/blood ; Cyclooxygenase 2/blood ; Cyclooxygenase Inhibitors/blood ; Cyclooxygenase Inhibitors/chemistry ; Cyclooxygenase Inhibitors/pharmacology ; Dinoprostone/antagonists & inhibitors ; Dinoprostone/metabolism ; Dose-Response Relationship, Drug ; Edema/chemically induced ; Edema/prevention & control ; Gastric Mucosa/drug effects ; Gastric Mucosa/metabolism ; Gastric Mucosa/pathology ; Humans ; In Vitro Techniques ; Inflammation/chemically induced ; Inflammation/prevention & control ; Male ; Molecular Structure ; Naphthalenes/blood ; Naphthalenes/chemistry ; Naphthalenes/pharmacology ; Naproxen/blood ; Naproxen/chemistry ; Naproxen/pharmacology ; Neutrophil Infiltration/drug effects ; Nitric Oxide Donors/blood ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology ; Protective Agents/chemistry ; Protective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasodilation/drug effects
    Chemical Substances Anti-Inflammatory Agents ; Cyclooxygenase Inhibitors ; NMI-1182 ; Naphthalenes ; Nitric Oxide Donors ; Protective Agents ; des-NO-NMI-1182 ; naproxen-n-butyl nitrate ; Naproxen (57Y76R9ATQ) ; Carrageenan (9000-07-1) ; Cyclooxygenase 1 (EC 1.14.99.1) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2005
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1080058-x
    ISSN 1568-5608 ; 0925-4692
    ISSN (online) 1568-5608
    ISSN 0925-4692
    DOI 10.1163/156856005774382661
    Database MEDical Literature Analysis and Retrieval System OnLINE

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