cyclopropanes

Summary

Top Publications

  1. ncbi Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
    Peter M A Calverley
    School of Clinical Sciences, Liverpool, UK
    Lancet 374:685-94. 2009
  2. ncbi Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials
    Leonardo M Fabbri
    University of Modena and Reggio Emilia, Modena, Italy
    Lancet 374:695-703. 2009
  3. ncbi The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease
    Armin Hatzelmann
    Nycomed GmbH, Konstanz, Germany
    Pulm Pharmacol Ther 23:235-56. 2010
  4. ncbi Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study
    Stuart A Montgomery
    Imperial College School of Medicine, University of London, London, United Kingdom
    J Clin Psychiatry 74:363-9. 2013
  5. ncbi Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease
    Peter M A Calverley
    Department of Medicine, Clinical Sciences, University Hospital Aintree, Liverpool L97AL, UK
    Am J Respir Crit Care Med 176:154-61. 2007
  6. ncbi Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study
    Gregory M Asnis
    Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, 111 East 210th St, Bronx, NY 10467, USA
    J Clin Psychiatry 74:242-8. 2013
  7. ncbi Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety
    A L Auclair
    Neuropsychopharmacology Division, Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres, France
    Neuropharmacology 70:338-47. 2013
  8. ncbi Roflumilast with long-acting β2-agonists for COPD: influence of exacerbation history
    E D Bateman
    University of Cape Town Lung Institute, Cape Town, South Africa
    Eur Respir J 38:553-60. 2011
  9. pmc Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD
    Stephen I Rennard
    Nebraska Medical Center, Omaha, Nebraska, USA
    Respir Res 12:18. 2011
  10. pmc Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis
    Xiao Hong Yu
    Department of Biochemistry and Cell Biology, Stony Brook University, NY, USA
    BMC Plant Biol 11:97. 2011

Detail Information

Publications285 found, 100 shown here

  1. ncbi Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
    Peter M A Calverley
    School of Clinical Sciences, Liverpool, UK
    Lancet 374:685-94. 2009
    ..We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD...
  2. ncbi Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials
    Leonardo M Fabbri
    University of Modena and Reggio Emilia, Modena, Italy
    Lancet 374:695-703. 2009
    ..The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated...
  3. ncbi The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease
    Armin Hatzelmann
    Nycomed GmbH, Konstanz, Germany
    Pulm Pharmacol Ther 23:235-56. 2010
    ..This enables roflumilast to offer effective, oral maintenance treatment for COPD, with an acceptable tolerability profile and the potential to favourably affect the extrapulmonary effects of the disease...
  4. ncbi Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study
    Stuart A Montgomery
    Imperial College School of Medicine, University of London, London, United Kingdom
    J Clin Psychiatry 74:363-9. 2013
    ..To investigate the efficacy and safety of levomilnacipran sustained release (SR), an antidepressant candidate in late-stage development, in major depressive disorder (MDD)...
  5. ncbi Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease
    Peter M A Calverley
    Department of Medicine, Clinical Sciences, University Hospital Aintree, Liverpool L97AL, UK
    Am J Respir Crit Care Med 176:154-61. 2007
    ..Whether treatment is effective in more severe COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages III and IV) over a longer period is unknown...
  6. ncbi Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study
    Gregory M Asnis
    Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, 111 East 210th St, Bronx, NY 10467, USA
    J Clin Psychiatry 74:242-8. 2013
    ....
  7. ncbi Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety
    A L Auclair
    Neuropsychopharmacology Division, Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres, France
    Neuropharmacology 70:338-47. 2013
    ..It is efficacious in models of anti-depressive/anti-stress activity, with minimal potential for locomotor side effects...
  8. ncbi Roflumilast with long-acting β2-agonists for COPD: influence of exacerbation history
    E D Bateman
    University of Cape Town Lung Institute, Cape Town, South Africa
    Eur Respir J 38:553-60. 2011
    ..No differences arose in adverse events between these subgroups. Roflumilast may be used to reduce exacerbations and improve dyspnoea and lung function, without increasing adverse events in COPD patients receiving concomitant LABAs...
  9. pmc Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD
    Stephen I Rennard
    Nebraska Medical Center, Omaha, Nebraska, USA
    Respir Res 12:18. 2011
    ..This led to the question of whether a responsive subset existed that could be investigated further...
  10. pmc Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis
    Xiao Hong Yu
    Department of Biochemistry and Cell Biology, Stony Brook University, NY, USA
    BMC Plant Biol 11:97. 2011
    ....
  11. pmc Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro
    J Milara
    Research Unit, University General Hospital Consortium, Valencia, Spain
    Br J Pharmacol 166:2243-62. 2012
    ....
  12. ncbi Monoamine-dependent, opioid-independent antihypersensitivity effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a postoperative pain model in rats
    Hideaki Obata
    Department of Anesthesiology, Gunma University Graduate School of Medicine, 3 39 22 Showa, Maebashi, Gunma 371 8511, Japan
    J Pharmacol Exp Ther 334:1059-65. 2010
    ..Combined administration of an SNRI with morphine might be a promising treatment to suppress postoperative hypersensitivity...
  13. pmc Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide
    A Buenestado
    Laboratory of Pulmonary Pharmacology UPRES EA220, Foch Hospital, University Versailles Saint Quentin, Suresnes, France
    Br J Pharmacol 165:1877-90. 2012
    ....
  14. pmc Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis
    Nadine Hertel
    IMS Consulting Group, London, UK
    Int J Chron Obstruct Pulmon Dis 7:183-99. 2012
    ..This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting...
  15. ncbi Towards selective antagonists of T-type calcium channels: design, characterization and potential applications of NNC 55-0396
    Ming Li
    Department of Pharmacology SL 83, Tulane University Health Science Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA
    Cardiovasc Drug Rev 23:173-96. 2005
    ..We conclude that NNC 55-0396, by virtue of its modified structure, does not produce the metabolite that causes inhibition of L-type Ca2+ channel channels, thus rendering it more selective to T-type Ca2+ channels...
  16. ncbi CHF5074, a novel gamma-secretase modulator, restores hippocampal neurogenesis potential and reverses contextual memory deficit in a transgenic mouse model of Alzheimer's disease
    Bruno P Imbimbo
    Research and Development, Chiesi Farmaceutici, Parma, Italy
    J Alzheimers Dis 20:159-73. 2010
    ..040). These effects were associated to a complete reversal of contextual memory deficit (p=0.006). Contextual memory significantly correlated with synaptophysin immunoreactivity in the cortex (r=0.548, p=0.0038)...
  17. ncbi Treatment of chronic obstructive pulmonary disease with roflumilast, a new phosphodiesterase 4 inhibitor
    Nicholas J Gross
    Department of Medicine, St Francis Hospital and Medical Center, Hartford, Connecticut 06105 1208, USA
    COPD 7:141-53. 2010
    ....
  18. ncbi Membrane cyclopropane fatty acid content is a major factor in acid resistance of Escherichia coli
    Y Y Chang
    Department of Microbiology, University of Illinois, Urbana 61801, USA
    Mol Microbiol 33:249-59. 1999
    ..Much, but not all, of this variability can be explained by the partially or totally defective RpoS alleles carried by many strains...
  19. pmc Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD
    Diana C Grootendorst
    Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
    Thorax 62:1081-7. 2007
    ..Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD...
  20. ncbi Inhibition of inflammation and remodeling by roflumilast and dexamethasone in murine chronic asthma
    Rakesh K Kumar
    Department of Pathology, University of New South Wales, Sydney, Australia
    J Pharmacol Exp Ther 307:349-55. 2003
    ..Roflumilast did not diminish accumulation of transforming growth factor-beta1, suggesting that it might affect remodeling by mechanisms distinct from glucocorticoids...
  21. ncbi The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain
    Hideaki Obata
    Department of Anesthesiology, Gunma University Graduate School of Medicine, 3 39 22 Showa, Maebashi, Gunma 371 8511, Japan
    Anesth Analg 100:1406-10, table of contents. 2005
    ..These findings suggest that simultaneous inhibition of serotonin and noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic effects. Milnacipran might be effective for suppression of neuropathic pain...
  22. pmc Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects
    Gail M Gauvreau
    Department of Medicine, McMaster University, Hamilton, Ontario, Canada
    Respir Res 12:140. 2011
    ..The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge...
  23. ncbi The γ-secretase modulator CHF5074 reduces the accumulation of native hyperphosphorylated tau in a transgenic mouse model of Alzheimer's disease
    Annamaria Lanzillotta
    Division of Pharmacology and Experimental Therapeutics, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia and Istituto Nazionale di Neuroscienze Brescia, Italy
    J Mol Neurosci 45:22-31. 2011
    ..Our data show that the novel γ-secretase modulator CHF5074 can fully reverse β-amyloid-associated tau pathology, thus representing a promising therapeutic agent for AD...
  24. pmc Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes
    Masayuki Wasa
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 133:19598-601. 2011
    ..of novel mono-N-protected amino acid ligands for Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. A diverse range of organoboron reagents can be used as coupling partners, and the reaction proceeds under ..
  25. pmc Ethylene-induced modulation of genes associated with the ethylene signalling pathway in ripening kiwifruit
    Xue Ren Yin
    Laboratory of Fruit Molecular Physiology and Biotechnology The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Biotechnology, Zhejiang University, Huajiachi Campus, Hangzhou 310029, PR China
    J Exp Bot 59:2097-108. 2008
    ..The ethylene-induced down-regulation of AdETR1 suggests that it may have a role in sensing ethylene and transmitting this response to other members of the receptor family, thus activating the signal transduction pathway...
  26. ncbi Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications
    Gianpiera Ceresoli-Borroni
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    J Neurosci Res 85:845-54. 2007
    ..Selective inhibitors of this enzyme may therefore provide neuroprotection in newborns and will also be useful for the experimental evaluation of the long-term effects of perinatal KP impairment...
  27. ncbi Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2
    M Yokoi
    Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto 606, Japan
    Science 273:645-7. 1996
    ..The mutant mice performed normally in water maze learning tasks. Thus, the presynaptic mGluR2 is essential for inducing LTD at the mossy fiber-CA3 synapses, but this hippocampal LTD does not seem to be required for spatial learning...
  28. ncbi The γ-secretase modulator CHF5074 restores memory and hippocampal synaptic plasticity in plaque-free Tg2576 mice
    Claudia Balducci
    Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy
    J Alzheimers Dis 24:799-816. 2011
    ..We conclude that the beneficial effects of CHF5074 treatment in young transgenic mice occurred at a stage that precedes plaque formation and were associated with a reduction in intraneuronal AβPP/Aβ and hyperphosphorylated tau...
  29. pmc LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing
    Sophie Seehase
    Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
    PLoS ONE 7:e43709. 2012
    ....
  30. ncbi Secretase-independent and RhoGTPase/PAK/ERK-dependent regulation of cytoskeleton dynamics in astrocytes by NSAIDs and derivatives
    Mathieu P Lichtenstein
    Institut de Neurociènces, Universitat Autonoma de Barcelona, Spain
    J Alzheimers Dis 22:1135-55. 2010
    ....
  31. pmc Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury
    J Cortijo
    Department of Pharmacology, University of Valencia, Spain
    Br J Pharmacol 156:534-44. 2009
    ..The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin-induced lung injury were explored in 'preventive' and 'therapeutic' protocols and compared with glucocorticoids...
  32. ncbi Peripheral nerve injury sensitizes the response to visceral distension but not its inhibition by the antidepressant milnacipran
    Sang Wook Shin
    Department of Anesthesiology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Anesthesiology 100:671-5. 2004
    ....
  33. ncbi Changes in membrane lipid composition in ethanol- and acid-adapted Oenococcus oeni cells: characterization of the cfa gene by heterologous complementation
    Cosette Grandvalet
    Laboratoire Recherche En Vigne et Vin, Universite de Bourgogne, Institut Universitaire de la Vigne et du Vin Jules Guyot, 1, Rue Claude Ladrey Campus Montmuzard, BP27877, F 21078 Dijon, France
    Microbiology 154:2611-9. 2008
    ..oeni. In spite of this partial complementation, the complemented strain of E. coli totally recovered its viability after ethanol shock (10 %, v/v) whereas its viability was only partly recovered after an acid shock at pH 3.0...
  34. ncbi Selective phosphodiesterase-4 inhibitors in chronic obstructive lung disease
    Francisco J Soto
    Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Curr Opin Pulm Med 11:129-34. 2005
    ..Novel anti-inflammatory therapies such as selective phosphodiesterase 4 (PDE4) inhibitors are in clinical development. Their potential role in the management of COPD is described in this review...
  35. ncbi Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial
    Jens M Hohlfeld
    Department of Clinical Airway Research, Fraunhofer Institute of Toxicology and Experimental Medicine ITEM, Nikolai Fuchs Street 1A, D 30625 Hannover, Germany
    Pulm Pharmacol Ther 21:616-23. 2008
    ..Roflumilast, an investigational, targeted phosphodiesterase 4 inhibitor, reduces the in vitro and in vivo inflammatory activity of cells such as neutrophils, eosinophils, macrophages, and monocytes...
  36. ncbi Acid habituation of Escherichia coli and the potential role of cyclopropane fatty acids in low pH tolerance
    J L Brown
    Department of Agricultural Science, University of Tasmania, Australia brown
    Int J Food Microbiol 37:163-73. 1997
    ..The results presented illustrate the remarkable capacity of E. coli to adapt to environmental challenges, and have significant implications for the survival of spoilage and pathogenic bacteria, and hence for food safety...
  37. ncbi A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro
    F Sabatini
    Pulmonary Disease Unit, G Gaslini Institute, Largo G Gaslini 5, 16147 Genoa, Italy
    Pulm Pharmacol Ther 23:283-91. 2010
    ..Taken together, these findings indicate that roflumilast N-oxide directly targets human lung fibroblasts, which may at least partially explain the efficacy of roflumilast to mitigate a pulmonary fibrotic response in vivo...
  38. pmc Carbocyclic fatty acids in plants: biochemical and molecular genetic characterization of cyclopropane fatty acid synthesis of Sterculiafoetida
    Xiaoming Bao
    Department of Plant Biology, Michigan State University, East Lansing, MI 48824, USA
    Proc Natl Acad Sci U S A 99:7172-7. 2002
    ..Together, a CPA-FA synthase was identified from S. foetida, and the pathway in higher plants that produce carbocyclic fatty acids was defined as by transfer of C(1) units, most likely from S-adenosylmethionine to oleate...
  39. pmc CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease
    B P Imbimbo
    Research and Development, Chiesi Farmaceutici, Via Palermo, Parma, Italy
    Br J Pharmacol 156:982-93. 2009
    ....
  40. ncbi Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by total phosphodiesterase-4 inhibitory activity and development of a population pharmacodynamic-adverse event model
    Gezim Lahu
    Department of Pharmacometrics and Pharmacokinetics, Nycomed GmbH, Byk Gulden Strasse 2, Konstanz, Germany
    Clin Pharmacokinet 49:589-606. 2010
    ..Both roflumilast and its metabolite roflumilast N-oxide have anti-inflammatory properties that contribute to overall pharmacological activity...
  41. pmc Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice
    Apoorva Bhatt
    Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 104:5157-62. 2007
    ..This long-term persistence of DeltakasB represents a model for studying latent M. tuberculosis infections and suggests that this attenuated strain may represent a valuable vaccine candidate against tuberculosis...
  42. pmc Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence
    Vivek Rao
    Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Clin Invest 116:1660-7. 2006
    ..tuberculosis-induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation...
  43. ncbi In vitro and in vivo profiling of CHF5022 and CHF5074 Two beta-amyloid1-42 lowering agents
    Bruno P Imbimbo
    Research and Development Department, Chiesi Farmaceutici, Via Palermo 26 A, 43100 Parma, Italy
    Pharmacol Res 55:318-28. 2007
    ..105) with CHF5022 concentration in the brain. CHF5022 and CHF5074 thus appear to have a promising in vitro and in vivo profile. This warrants further evaluation of their long-term effects on Abeta brain pathology...
  44. pmc Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects
    Nassr Nassr
    Nycomed GmbH, 78467 Konstanz, Germany
    Br J Clin Pharmacol 68:580-7. 2009
    ..Roflumilast is metabolized by CYP3A4 and CYP1A2, with further involvement of CYP2C19 and extrahepatic CYP1A1. In vivo, roflumilast N-oxide contributes >90% to the total PDE4 inhibitory activity...
  45. pmc Stereospecific formation of the (R)-gamma-hydroxytrimethylene interstrand N2-dG:N2-dG cross-link arising from the gamma-OH-1,N2-propano-2'-deoxyguanosine adduct in the 5'-CpG-3' DNA sequence
    Hai Huang
    Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235, USA
    J Am Chem Soc 131:8416-24. 2009
    ..The formation of this hydrogen bond may, in part, explain the thermal stability of this carbinolamine interstrand cross-link and the stereochemical preference for the (R) configuration of the cross-link...
  46. pmc Novel cyclopropane fatty acids from the phospholipids of the Caribbean sponge Pseudospongosorites suberitoides
    Néstor M Carballeira
    Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, PO Box 23346, San Juan, 00931 3346 Puerto Rico
    Lipids 42:519-24. 2007
    ..The novel cyclopropyl fatty acids could have originated from the phospholipids of a cyanobacterium living in symbiosis with the sponge...
  47. ncbi PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease
    Katharine H Banner
    Pfizer Global Research and Development, Discovery Biology, Allergy and Respiratory Group, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK
    Trends Pharmacol Sci 25:430-6. 2004
    ..In this review, we summarize for the first time the evidence that PDE4 inhibitors might have therapeutic benefit in IBD, and discuss mechanisms of action beyond the inhibition of inflammatory cells...
  48. ncbi Vinylcyclopropane derivatives in transition-metal-catalyzed cycloadditions for the synthesis of carbocyclic compounds
    Lei Jiao
    College of Chemistry, Peking University, Beijing 100871, China
    J Org Chem 78:6842-8. 2013
    ..A tabular summary of applications of the VCP cycloadditions in natural product synthesis is also presented. ..
  49. ncbi Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation
    Hyun Jeong Kwak
    Laboratory of Molecular Pharmacology and Physiology, Medicinal Science Division, Korea Research Institute of Chemical Technology, P O Box 107, Yusung Gu, TaeJon 305 343, Korea
    J Pharmacol Exp Ther 315:1188-95. 2005
    ..These results suggest that the inhibitory activity of roflumilast on the production of inflammatory mediators seems to be mediated via inhibition of NF-kappaB, p38 MAP kinase, and JNK activation in macrophages...
  50. ncbi Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition of 1-yne/ene-vinylcyclopropanes and CO: homologous Pauson-Khand reaction and total synthesis of (+/-)-alpha-agarofuran
    Lei Jiao
    Beijing National Laboratory of Molecular Sciences BNLMS, Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, Beijing 100871, China
    Org Lett 12:2528-31. 2010
    ....
  51. ncbi Additive anti-inflammatory effects of beta 2 adrenoceptor agonists or glucocorticosteroid with roflumilast in human peripheral blood mononuclear cells
    Stacey L Tannheimer
    Respiratory Research, Gilead Sciences Inc, 199 East Blaine St, Seattle, WA 98102, USA
    Pulm Pharmacol Ther 25:178-84. 2012
    ..Addition of roflumilast to either a β2 adrenoceptor agonist or a glucocorticosteroid may provide superior anti-inflammatory activity and greater efficacy in COPD patients and be dose sparing...
  52. ncbi Isolation of C₁₁ compounds and a cyclopropane fatty acid from an Okinawan ascidian, Diplosoma sp
    Tamanna Rob
    Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara cho Okinawa 903 0123, Japan
    Molecules 16:9972-82. 2011
    ..The structures of 1-5 were determined by spectroscopic analysis and/or synthesis. Compound 1 inhibited the division of fertilized sea urchin eggs and compound 4 showed mild cytotoxity against HCT116 cells (human colorectal cancer cell)...
  53. ncbi Carbon dioxide action on ethylene biosynthesis of preclimacteric and climacteric pear fruit
    Hans P J de Wild
    Agrotechnological Research Institute ATO, PO Box 17, 6700 AA Wageningen, The Netherlands
    J Exp Bot 54:1537-44. 2003
    ..Kinetic parameters derived from the models point to the conversion from ACC to ethylene by ACC oxidase as a possible action site for CO2 inhibition...
  54. ncbi 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity
    Bruno P Imbimbo
    Research and Development, Chiesi Farmaceutici, Via Palermo 26 A, 43100 Parma, Italy
    J Pharmacol Exp Ther 323:822-30. 2007
    ..CHF5074 is therefore a promising therapeutic agent for Alzheimer's disease...
  55. ncbi Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: facile access to spiro 3,3'-cyclopropyl oxindoles
    Carolyn L Ladd
    Centre in Green Chemistry and Catalysis, Department of Chemistry, Universite de Montreal, P O Box 6128 Station Downtown, Montreal, Quebec, H3C 3J7, Canada
    Org Lett 15:1350-3. 2013
    ..The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway...
  56. pmc Roflumilast-N-oxide induces surfactant protein expression in human alveolar epithelial cells type II
    Kerstin Höhne
    Division of Internal Medicine, Department of Pneumology, University Medical Centre, Freiburg, Germany
    PLoS ONE 7:e38369. 2012
    ..Roflumilast-N-oxide fosters the expression of SPs in human AEC-II via increase of intracellular cAMP levels potentially contributing to improved alveolar host defence and enhanced resolution of inflammation...
  57. ncbi Frequency facilitation at mossy fiber-CA3 synapses of freely behaving rats is regulated by adenosine A1 receptors
    Jens Klausnitzer
    Department of Experimental Neurophysiology, Medical Faculty, Ruhr University Bochum, 44780 Bochum, Germany
    J Neurosci 28:4836-40. 2008
    ....
  58. ncbi No dose adjustment on coadministration of the PDE4 inhibitor roflumilast with a weak CYP3A, CYP1A2, and CYP2C19 inhibitor: an investigation using cimetidine
    Gabriele M Böhmer
    Department of Clinical Pharmacology, University Hospital of Tubingen, Tubingen, Germany
    J Clin Pharmacol 51:594-602. 2011
    ..These moderate changes indicate that dose adjustment of roflumilast is not required when coadministered with a weak inhibitor of CYP1A2, CYP3A, and CYP2C19, such as cimetidine...
  59. ncbi Phosphodiesterase type 4 inhibitors cause proinflammatory effects in vivo
    Kerryn McCluskie
    Department of Pharmacology, Theravance Inc, South San Francisco, California, USA
    J Pharmacol Exp Ther 319:468-76. 2006
    ..The proinflammatory cytokines KC and IL-8 therefore may provide surrogate biomarkers, both in preclinical animal models and in the clinic, to assess potential proinflammatory effects of this class of compounds...
  60. ncbi Phospholipid modifications in bacteria
    John E Cronan
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, Illinois 61801, USA
    Curr Opin Microbiol 5:202-5. 2002
    ..Cyclopropanation has been shown to play a role in Mycobacterium tuberculosis pathogenesis and, in Escherichia coli, plays an important role in resistance to acidic conditions...
  61. ncbi Inhibition of the ethylene response by 1-MCP in tomato suggests that polyamines are not involved in delaying ripening, but may moderate the rate of ripening or over-ripening
    Annalisa Tassoni
    Department of Plant Biology, Cornell University, Ithaca, NY 14853, USA
    J Exp Bot 57:3313-25. 2006
    ..No effect of treatment on ornithine decarboxylase activity was detected. Polyamines are thus not directly associated with a delay in tomato fruit ripening, but may prolong the fully-ripe stage before the fruit tissues undergo senescence...
  62. pmc Cyclopropane ring formation in membrane lipids of bacteria
    D W Grogan
    Department of Biological Sciences, University of Cincinnati, Ohio 45221 0006, USA
    Microbiol Mol Biol Rev 61:429-41. 1997
    ....
  63. ncbi Cloning and functional analysis of 9-cis-epoxycarotenoid dioxygenase (NCED) genes encoding a key enzyme during abscisic acid biosynthesis from peach and grape fruits
    Mei Zhang
    College of Agronomy and Biotechnology, China Agricultural University, Beijing 100094, China
    J Plant Physiol 166:1241-52. 2009
    ....
  64. pmc Differential expression and internal feedback regulation of 1-aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, and ethylene receptor genes in tomato fruit during development and ripening
    A Nakatsuka
    Laboratory of Postharvest Agriculture, Faculty of Agriculture, Okayama University, Tsushima, Okayama, 700 8530 Japan
    Plant Physiol 118:1295-305. 1998
    ..This transition from system 1 to system 2 ethylene production might be related to the accumulated level of NR mRNA...
  65. ncbi Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease
    Brian J Lipworth
    Department of Medicine and Therapeutics, Asthma and Allergy Research Group, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    Lancet 365:167-75. 2005
    ..Ultimately, clinicians will want to know whether PDE4 inhibitors are anything more than expensive "designer" theophylline, the archetypal non-selective phosphodiesterase inhibitor...
  66. pmc Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability
    M J Sanz
    Department of Pharmacology, University of Valencia, Valencia, Spain
    Br J Pharmacol 152:481-92. 2007
    ..The present study addressed the effects of the investigational PDE4 inhibitor roflumilast on leukocyte-endothelial cell interactions and endothelial permeability in vivo and in vitro...
  67. ncbi The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial
    Philip J Mease
    Seattle Rheumatology Associates, 1101 Madison Street, Suite 1000, Seattle, WA 98104, USA
    J Rheumatol 36:398-409. 2009
    ..To evaluate the safety and efficacy of milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM)...
  68. ncbi Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors
    Georgia M Alexander
    Neuroscience Program, Wake Forest University School of Medicine, Medical Center Blvd Winston Salem, NC 27157, USA
    J Neurophysiol 94:163-75. 2005
    ..This presynaptic inhibition may partially mute sensory feedback and prevent reentrant excitation from initiating abnormal thalamic rhythms...
  69. ncbi Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions
    Emmerentia van Schalkwyk
    Department of Internal Medicine, University of Stellenbosch, Cape Town
    J Allergy Clin Immunol 116:292-8. 2005
    ..Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling...
  70. ncbi The discovery and development of compounds counteracting ethylene at the receptor level
    Edward C Sisler
    Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27695 7722, USA
    Biotechnol Adv 24:357-67. 2006
    ..1-MCP is likely to remain a primary means of controlling ethylene responses for the immediate future...
  71. ncbi Stereocontrolled synthesis of 3-(trans-2-aminocyclopropyl)alanine, a key component of belactosin A
    Alan Armstrong
    Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK
    Org Lett 5:2331-4. 2003
    ..reaction: see text]..
  72. ncbi Ethylene is required for both the initiation and progression of softening in pear (Pyrus communis L.) fruit
    Kyoko Hiwasa
    Graduate School of Natural Science and Technology, Okayama University, Tsushima, Okayama 700 8530, Japan
    J Exp Bot 54:771-9. 2003
    ..The results suggest that ethylene is required for PGs expression even in the late ripening stage, but not for EGases...
  73. ncbi PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression
    Maria Jesus Sanz
    Department of Pharmacology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibanez 15, E 46010 Valencia, Spain
    Pharmacol Ther 106:269-97. 2005
    ..These new drugs may also offer opportunities for treatment of other inflammatory diseases...
  74. ncbi Gold(I)-catalyzed stereoselective olefin cyclopropanation
    Magnus J Johansson
    Department of Chemistry, University of California, Berkeley, California 94720, USA
    J Am Chem Soc 127:18002-3. 2005
    ..This reaction provided the basis for the use of a DTBM-SEGPHOS gold(I) complex as a catalyst in the enantioselective (up to 94% ee) preparation of vinyl cyclopropanes with high cis-selectivity.
  75. ncbi Involvement of negative feedback regulation in wound-induced ethylene synthesis in 'Saijo' persimmon
    Qiao Lin Zheng
    The United Graduate School of Agricultural Sciences, Tottori University, Japan
    J Agric Food Chem 54:5875-9. 2006
    ..Out of accord with DK-ACO1 gene expression, ACC oxidase activity was enhanced 48 h after wounding in 1-MCP pretreated tissues, reaching a peak 1.5-fold higher than that in control tissues at 60 h...
  76. ncbi The oral, once-daily phosphodiesterase 4 inhibitor roflumilast lacks relevant pharmacokinetic interactions with inhaled budesonide
    Robert Hermann
    ALTANA Pharma AG, Konstanz, Germany
    J Clin Pharmacol 47:1005-13. 2007
    ..67, 1.50). Coadministration of roflumilast and budesonide did not alter the steady-state disposition of each other and did not affect safety and tolerability of either drug...
  77. ncbi Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors
    J Nicole Hamblin
    GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
    Bioorg Med Chem Lett 18:4237-41. 2008
    ....
  78. ncbi Efficacy and safety of roflumilast in the treatment of asthma
    Eric D Bateman
    Division of Pulmonology, Department of Medicine, University of Cape Town, South Africa
    Ann Allergy Asthma Immunol 96:679-86. 2006
    ..Roflumilast is an oral, once-daily phosphodiesterase type 4 inhibitor with anti-inflammatory activity in preclinical models of asthma and chronic obstructive pulmonary disease...
  79. ncbi Differential feedback regulation of ethylene biosynthesis in pulp and peel tissues of banana fruit
    Akitsugu Inaba
    Faculty of Agriculture, Okayama University, Tsushima, Okayama, 700 8530 Japan
    J Exp Bot 58:1047-57. 2007
    ..This differential regulation by ethylene in pulp and peel tissues was also observed for MA-PL, MA-Exp, and MA-MADS genes...
  80. ncbi Transcriptional regulation of ethylene receptor and CTR genes involved in ethylene-induced flower opening in cut rose (Rosa hybrida) cv. Samantha
    Nan Ma
    Department of Ornamental Horticulture, China Agricultural University, Beijing 100094, China
    J Exp Bot 57:2763-73. 2006
    ..Samantha, and that continued ethylene perception results in flower opening. Ethylene may regulate flower opening mainly through expression of two ethylene receptor genes (Rh-ETR1 and Rh-ETR3) and two CTR (Rh-CTR1 and Rh-CTR2) genes...
  81. ncbi Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide
    Oliver von Richter
    Exploratory Medicine, ALTANA Pharma AG, Konstanz, Germany
    Clin Pharmacokinet 46:613-22. 2007
    ....
  82. pmc Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice
    Piero A Martorana
    Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy
    BMC Pulm Med 8:17. 2008
    ..Here we investigated the effects of roflumilast on the volume density (VV) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure...
  83. ncbi Metabotropic glutamate receptors stimulate phospholipase D via different pathways in the adult and neonate rat hippocampus
    S Attucci
    Dipartimento di Farmacologia Preclinica e Clinica, , Italy
    Neurochem Res 26:1151-5. 2001
    ..Our results lend support to the hypothesis that glutamatergic activation of PLD in the rat hippocampus is developmentally regulated...
  84. ncbi Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin and p16) and CCL27 in alopecia areata before and after diphencyprone treatment: an immunohistochemical study
    O Simonetti
    Clinica Dermatologica, Universita Politecnica delle Marche, Ospedale Regionale, Via Conca 20, 60020 Torrette, Ancona, Italy
    Br J Dermatol 150:940-8. 2004
    ..The cutaneous lymphocyte-associated antigen (CLA) and the skin-associated chemokine CCL27 highlight an important role for epithelial cells in controlling homeostatic lymphocyte trafficking...
  85. ncbi PDE4 inhibitors: a review of current developments (2005 - 2009)
    Lluís Pagès
    Almirall R and D Centre, Department of Medicinal Chemistry, Laurea Miro 408 410, 08980 Sant Feliu de Llobregat, Barcelona, Spain
    Expert Opin Ther Pat 19:1501-19. 2009
    ..Despite the sound preclinical database and some promising data from clinical trials, development of PDE4 inhibitors for the treatment of inflammatory or neurological diseases has been hampered by dose-limiting class-related side effects...
  86. ncbi Laboratory and field evaluation of spatial repellency with metofluthrin-impregnated paper strip against mosquitoes in Lombok Island, Indonesia
    Hitoshi Kawada
    Department of Vector Ecology and Environment, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Nagasaki 852 8523, Japan
    J Am Mosq Control Assoc 20:292-8. 2004
    ..Metofluthrin treatment reduced mosquito collection by >80% during the 1st 4 weeks. However, repellency seemed to reduce with the loss of metofluthrin by evaporation within 6 wk after treatment...
  87. ncbi Evidence that phospholipase D activation prevents group I mGluR-induced persistent prolongation of epileptiform bursts
    Marjorie J Rico
    Neural and Behavioral Science Program, School of Graduate Studies, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
    J Neurophysiol 91:2385-8. 2004
    ..Hence, PLD activation with CSA may prevent the synthesis of a protein critical for the induction of group I mGluR-mediated epileptogenesis...
  88. ncbi Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide
    Gezim Lahu
    Nycomed GmbH, Konstanz, Germany
    J Clin Pharmacol 51:586-93. 2011
    ..Roflumilast was well tolerated both alone and in combination with enoxacin. A weak interaction was shown between roflumilast and enoxacin, as mean tPDE4i increased by 25%, but is unlikely to have clinical relevance...
  89. ncbi Roflumilast fully prevents emphysema in mice chronically exposed to cigarette smoke
    Piero A Martorana
    Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro 6, I 53100 Siena, Italy
    Am J Respir Crit Care Med 172:848-53. 2005
    ..There is a need for new agents capable of suppressing the inflammatory response in chronic obstructive pulmonary disease...
  90. ncbi MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis
    Y Yuan
    Tuberculosis Research Unit, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA
    J Biol Chem 272:10041-9. 1997
    ....
  91. ncbi Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge
    C Louw
    Internal Medicine, Lung and Allergy Unit, University of Stellenbosch, School of Medicine, Cape Town, South Africa
    Respiration 74:411-7. 2007
    ..Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma...
  92. ncbi The use of topical diphenylcyclopropenone for the treatment of extensive alopecia areata
    C Cotellessa
    Department of Dermatology, University of L Aquila, Italy
    J Am Acad Dermatol 44:73-6. 2001
    ..Highly variable results of topical diphenylcyclopropenone (DPCP) in the treatment of alopecia areata have been reported so far...
  93. pmc Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis
    Y Yuan
    Laboratory of Intracellular Parasites, National Institutes for Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA
    Proc Natl Acad Sci U S A 92:6630-4. 1995
    ..M. smegmatis overexpressing the cma1 gene product significantly resist killing by hydrogen peroxide, suggesting that this modification may be an important adaptation of slow-growing mycobacteria to oxidative stress...
  94. pmc Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects
    Nassr Nassr
    ALTANA Pharma AG, 78467 Konstanz, Germany
    Br J Clin Pharmacol 63:365-70. 2007
    ..The aim of this study was to investigate the effects of roflumilast, an investigational PDE4 inhibitor for the treatment of COPD and asthma, on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites...
  95. ncbi Steady-state pharmacokinetics of roflumilast and roflumilast N-oxide in patients with mild and moderate liver cirrhosis
    Robert Hermann
    Exploratory Medicine, ALTANA Pharma AG, Konstanz, Germany
    Clin Pharmacokinet 46:403-16. 2007
    ..Roflumilast is being developed for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease and asthma...
  96. ncbi Restoration of hair growth with topical diphencyprone in mouse and rat models of alopecia areata
    Liren Tang
    Division of Dermatology, University of British Columbia, Vancouver Hospital and Health Sciences Center, 835 W 10th Avenue, Vancouver, BC, Canada V5Z 4E8
    J Am Acad Dermatol 49:1013-9. 2003
    ..The contact sensitizer, diphencyprone (DPCP), is one of the most effective therapies for the more severe forms of alopecia areata (AA)...
  97. ncbi Diphenylcyclopropenone treatment of alopecia areata induces apoptosis of perifollicular lymphocytes
    Verena Herbst
    Dept of Dermatology, Philipp University, Deutschhausstrasse 9, 35033 Marburg, Germany
    Eur J Dermatol 16:537-42. 2006
    ..In addition the replacement with newly activated autoreactive T-cells might be impaired due to a DCP-mediated hindrance of APC emigration...
  98. ncbi Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects
    T D Bethke
    ALTANA Pharma AG, Konstanz, Germany
    Int J Clin Pharmacol Ther 44:572-9. 2006
    ..Therefore, this study investigated the pharmacokinetic characteristics of roflumilast and its pharmacodynamically active metabolite roflumilast N-oxide when co-administered with orally inhaled salbutamol in healthy subjects...
  99. ncbi The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2
    K M George
    Laboratory of Intracellular Parasites, NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA
    J Biol Chem 270:27292-8. 1995
    The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain...
  100. ncbi In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor
    D S Bundschuh
    Department of Pharmacology, Byk Gulden, P O Box 10 03 10, 78403 Konstanz, Germany
    J Pharmacol Exp Ther 297:280-90. 2001
    ..These results, coupled with the in vitro effects of roflumilast on inflammatory cells, suggest that roflumilast represents a potential new drug for the treatment of asthma and chronic obstructive pulmonary disease...
  101. ncbi Priming of group 2 metabotropic glutamate receptors facilitates induction of long-term depression in the dentate gyrus of freely moving rats
    D Manahan-Vaughan
    Leibniz Institute for Neurobiology, Department of Neurophysiology, Magdeburg, Germany
    Neuropharmacology 37:1459-64. 1998
    ..The present study demonstrates that priming of group 2 mGluRs leads to induction of persistent LTD in the dentate gyrus in vivo, consistent with a role for group 2 mGluRs in metaplasticity...

Research Grants63

  1. Efficient Assemblage of Complex Biologically-Active Targets Using Donor-Acceptor
    KEITH THOMAS MEAD; Fiscal Year: 2012
    ..We will begin by preparing cyclopropanes that are geminally substituted with ester and diethoxyphosphoryl groups and study their rearrangement to ?-..
  2. Development of Cyclopropyl Metal Carbene Based Methods for Organic Synthesis
    Weiping Tang; Fiscal Year: 2013
    ..broad range of mechanistically unique pathways and improves our fundamental understanding for the chemistry of cyclopropanes and metal carbenes...
  3. DEVELOPING AN UNDERSTANDING OF ASYMMETRIC INDUCTION
    Patrick J Walsh; Fiscal Year: 2010
    ..We have developed one-pot synthesis of a-hydroxy ketones, allylic alcohols, and substituted cyclopropanes from a versatile 1-alkenyl-1,1-bimetallic intermediate...
  4. SELECTIVE METHODS FOR SYNTHESIS WITH STRAINED MOLECULES AND CARBENOIDS
    Joseph M Fox; Fiscal Year: 2012
    ..Because Rh-carbeniods are critical to the synthesis of cyclopropenes and cyclopropanes, addressing the limitations of the chemistry of Rh-carbenes is a fundamental component to advancing the ..
  5. Group (IV) Imido Complex-Mediated Syntheses of Nitrogen-Containing Heterocycles
    JENNIFER SCHOMAKER; Fiscal Year: 2009
    ..The proposed research will examine the addition of group (IV) imido complexes to alkenes and strained cyclopropanes to form azametallacyclobutanes and pentanes...
  6. APPLICATIONS OF IRON COMPLEXES TO ORGANIC SYNTHESIS
    William Donaldson; Fiscal Year: 2001
    ..adjacent and remote to a conjugated diene; c) to control the relative stereochemistry of trisubstituted cyclopropanes; d) to control the relative stereochemistry at asymmetric centers adjacent to a trans-disubstituted ..
  7. 2 + 3 ANNULATION PROTOCOL--NATURAL PRODUCT SYNTHESIS
    Tomas Hudlicky; Fiscal Year: 1992
    ..c. Investigation of fluoride- catalyzed rearrangements of silyl-enol-ether-terminated vinyl-cyclopropanes and vinyl-oxiranes and insight into mechanistic details of this process. d...
  8. SYNTHESIS OF BIOLOGICALLY IMPORTANT DIHYDROBENZOFURANS
    Thomas Engler; Fiscal Year: 1991
    A study is proposed of the Lewis acid catalyzed reactions of various alkenes and cyclopropanes with methoxy-1,4-benzoquinones to selectively yield dihydrobenzofurans A-C and chromans D-F, respectively...
  9. Asymmetric Synthesis of Nitrogen Heterocycles
    Tomislav Rovis; Fiscal Year: 2013
    ..in metal-catalyzed [4+2] reactions;and 4) Implement isocyanate cycloadditions to involve allenes and vinyl cyclopropanes. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high ..
  10. Thiourea-Catalyzed Nucleophilic Desymmetrization of Meso-Cyclopropanes
    KRISTINE NOLIN; Fiscal Year: 2008
    ..of stereoselective 1,5-functionalization of carbonyls through thiourea catalyzed desymmetrizations of meso-cyclopropanes by nucleophilic ring opening...
  11. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  12. SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENT
    Paul Wender; Fiscal Year: 2005
    ..Overall, this research program is expected to be of significant value in chemistry, biology, and medicine. ..
  13. PHYSIOLOGICALLY ACTIVE NATURAL PRODUCTS
    Douglass Taber; Fiscal Year: 2007
    ..In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates. ..
  14. Catalytic Processes for Selective Organic Synthesis
    GARY MOLANDER; Fiscal Year: 2005
    ..4) Carbometalation/cyclization reactions will be explored utilizing organochromium species. 5) Ligands and catalytic systems designed for asymmetric synthesis will be explored. ..
  15. General Anesthetics and nAcCHOR Agonist Affinity
    Douglas Raines; Fiscal Year: 2004
    ....
  16. NEW RHODIUM-CATALYZED ALLYLIC ALKYLATION REACTIONS
    P Evans; Fiscal Year: 2006
    ..The development of a temporary silicon-tethered (TST) rhodium-catalyzed [4+2+2] carbocyclization approach to the diterpene, epoxydictymene. ..
  17. STEREOSELECTIVE SYNTHESIS OF CYCLIC ETHERS
    P Evans; Fiscal Year: 2006
    ..Finally, we will examine a series bismuth-catalyzed bis-reductive etherification reactions for the construction of linear fused polycyclic ethers. ..
  18. DEVELOPMENT OF A LIVE ATTENUATED HSV-2 VACCINE
    Mark Prichard; Fiscal Year: 2002
    ..In addition further in vitro characterization will enable high quality clinical trial material to be produced for IND enabling primate studies and early Phase I human trials. PROPOSED COMMERCIAL APPLICATION: Not Available ..
  19. SYNTHESIS OF NATURAL PRODUCTS WITH OXAZOLE MOIETIES
    Peter Wipf; Fiscal Year: 2005
    ..The proposed program represents a multi-dimensional effort to increase the basic knowledge of the function of marine natural products, establish new methods in heterocyclic chemistry, and identify novel pharmacophores. ..
  20. Agilent 5973 GC/MS System
    GARY MOLANDER; Fiscal Year: 2002
    ..Our current lack of such instrumentation negatively affects the ability to carry out many of these studies. This critical capability, in the form of an instrument for everyday analysis, is urgently needed. ..
  21. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    ALAN PAUL KOZIKOWSKI; Fiscal Year: 2010
    ....
  22. 400 MHZ NMR SPECTROMETER
    Rodney Johnson; Fiscal Year: 2008
    ..Their research addresses a number of different disease areas including Parkinson's disease, schizophrenia, pain, pulmonary fibrosis, anticancer therapy, carcinogenesis, and tuberculosis. [unreadable] [unreadable] [unreadable]..
  23. Novel Animal Model System of AIDS-Kaposi Sarcoma
    Patricio Ray; Fiscal Year: 2005
    ....
  24. ASYMMETRIC SYNTHESIS OF IONOPHORE/MACROLIDE ANTIBIOTICS
    David Evans; Fiscal Year: 2005
    ..Our goal has been to set in place all of the reactions necessary for the rapid assemblage of any polyketide target structure. ..
  25. Tandem Cycloaddition Chemistry of 2-Azoniaheterodienes
    SCOTT DENMARK; Fiscal Year: 2007
    ..abstract_text> ..
  26. Cross-Coupling Reactions of Organosilanols
    SCOTT DENMARK; Fiscal Year: 2009
    ..Synthetic approaches to isodomoic acid H, hepatitis C viral inihibiting indole alkaloids, the salicylihalimide macrolactone oximidine II, and polyene antiviral antibiotic viridenomycin are detailed. ..
  27. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2007
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  28. ACYCLIC STEREOCONTROL IN RADICAL REACTIONS
    MUKUND SIBI; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  29. S-Adenosyl Methionine(SAMe)Augmentation of SSRIs in MDD
    George Papakostas; Fiscal Year: 2008
    ..It is hoped that this project award will provide the critical fund of basic knowledge and practical experience necessary to aid the candidate in becoming an independent investigator in this area. ..
  30. Novel Inhibitors of Staphylococcal Biofilm Formation
    John Williams; Fiscal Year: 2008
    ..The innovation of this proposal is to develop drugs that specifically target the biofilm mode of growth to prevent biofilm-related infections. [unreadable] [unreadable] [unreadable]..
  31. Light activated bioactive substrate release
    RICHARD GIVENS; Fiscal Year: 2008
    ..abstract_text> ..
  32. Synthesis of Polyketides and Terpenes
    David A Evans; Fiscal Year: 2010
    ..As a consequence, organic synthesis is a critical discipline that continues to have an important impact on the fields of both medicine and biology. ..
  33. ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS
    David Evans; Fiscal Year: 2001
    ..During the course of this project we intend to confirm (correct) the absolute stereochemical assignments of the principal members of this family by total synthesis. ..
  34. Distal Lung Inflammation Effect on Asthma Exacerbations
    Donald Tashkin; Fiscal Year: 2008
    ..This study has the potential to clarify the contribution of the "silent zone" to the persistent morbidity encountered with asthma. ..
  35. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2008
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  36. Nicotinic Receptors in Parkinson's Disease
    Maryka Quik; Fiscal Year: 2007
    ..These data together with the results of the behavioral studies may form a basis for the use of nicotinic drugs in the treatment of Parkinson's disease. [unreadable] [unreadable]..
  37. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
    ..abstract_text> ..
  38. Fostriecin and Related Protein Phosphatase Inhibitors
    Dale Boger; Fiscal Year: 2005
    ....
  39. SCLERODERMA LUNG STUDY
    Donald Tashkin; Fiscal Year: 2003
    ..abstract_text> ..
  40. COMBINATORIAL APPROACHES TO ANTI-SMALLPOX AGENTS
    Michael Pirrung; Fiscal Year: 2003
    ....
  41. CHEMISTRY-BIOLOGY INTERFACE TRAINING PROGRAM
    Michael Pirrung; Fiscal Year: 2003
    ..It is intended to train future leaders in pharmaceutical, medical, and biotechnological research to serve in academia, government, and industry. ..
  42. Peptidomimetics of D-Ala-D-Ala as Novel Antibacterials
    Norma Dunlap; Fiscal Year: 2003
    ..This would have a significant impact in the ability to treat bacterial infections. ..
  43. THERAPEUTIC TARGETS TO PREVENT BREAST CANCER METASTASIS
    JOSEPH PENTO; Fiscal Year: 2002
    ....
  44. CHRONIC LOW BACK PAIN AS A MODEL OF FIBROMYALGIA
    Daniel Clauw; Fiscal Year: 2002
    ..abstract_text> ..
  45. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001
    ..abstract_text> ..
  46. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 2001
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  47. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
    ....
  48. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2004
    ....
  49. Nicotinic and neuroprotection in a parkinson mouse model
    Maryka Quik; Fiscal Year: 2007
    ..This may allow for the design of neuroprotective strategies for PD, a disorder for which only symptomatic treatment is currently available. ..
  50. Iron and Vitamin E in Childhood HIV-Associated Renal Disease
    Patricio Ray; Fiscal Year: 2006
    ..The proposed studies should have a substantial impact on the goals of the National Center for Complementary and Alternative Medicine and NIH, according to the program announcement PA-02-124. [unreadable] [unreadable]..
  51. Medicinal Chemistry and Biology of Oral Insulin Mimics
    Michael Pirrung; Fiscal Year: 2006
    ..They would therefore increase the reliability of diabetes management, particularly for children. ..
  52. Mechanisms of Acupuncture Analgesia
    Richard Harris; Fiscal Year: 2006
    ..There is a strong institutional commitment to see the applicant succeed in this task due to a tremendous need for well-trained clinical investigators in alternative and complementary medicine. ..
  53. BIOORGANIC CHEMISTRY OF ANTIBACTERIALS
    Michael Pirrung; Fiscal Year: 2001
    ..An ancillary benefit of this project will be the development of novel techniques in solid phase synthesis through the total synthesis of natural products. ..
  54. Postsynthetic Modifications of Bacterial Membrane Lipids
    John Cronan; Fiscal Year: 2006
    ..These processes will be studied by a combination of biochemical, genetic, and molecular biological approaches including tests of pathogenesis in a mouse model system ..
  55. AMBIENT PARTICULATE MATTERS POISON CARDIAC ION CHANNELS
    Desuo Wang; Fiscal Year: 2005
    ....
  56. INFLAMMATION & CORTICOSTEROID RESPONSES IN SEVERE ASTHMA
    KIAN CHUNG; Fiscal Year: 2005
    ..The molecular mechanisms underlying loss of CR will be examined. These studies should lead to more effective therapies for chronic severe asthma. ..
  57. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2002
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  58. NEW AMINO-PROTECTING GROUPS AND COUPLING REAGENTS
    LOUIS CARPINO; Fiscal Year: 2009
    ..Microwave irradiation is expected to allow for the most efficient syntheses, especially with Bsmoc and HOAt-based chemistry. ..
  59. The Michigan Clinical Research Collaboratory
    Daniel Clauw; Fiscal Year: 2004
    ..Disseminate findings, tools, and strategies from this project to other re-engineered networks and Research Centers, and ultimately interface with a National Electronics Clinical Trials and Research (NECTAR) network...