cyclic s oxides

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Top Publications

  1. ncbi Activation of ATP-sensitive K+ channels in the ventromedial hypothalamus amplifies counterregulatory hormone responses to hypoglycemia in normal and recurrently hypoglycemic rats
    Rory J McCrimmon
    Department of Internal Medicine and Endocrinology, Yale University School of Medicine, Section of Endocrinology, P O Box 208020, New Haven, CT 06520 8020, USA
    Diabetes 54:3169-74. 2005
  2. ncbi Potent and selective activation of the pancreatic beta-cell type K(ATP) channel by two novel diazoxide analogues
    M Dabrowski
    University Laboratory of Physiology, Parks Road, Oxford, UK
    Diabetologia 46:1375-82. 2003
  3. ncbi The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener, in healthy male subjects
    Milan Zdravkovic
    Novo Nordisk A S, Medical Development, Bagsvaerd, Denmark
    J Clin Pharmacol 45:763-72. 2005
  4. ncbi [Creation of functional organic compounds and their applications]
    Hiroaki Takayama
    Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, 1091 1 Suarashi, Sagamiko machi, Thukui gun, Kanagawa 199 0195, Japan
    Yakugaku Zasshi 122:127-55. 2002
  5. ncbi BPDZ 154 activates adenosine 5'-triphosphate-sensitive potassium channels: in vitro studies using rodent insulin-secreting cells and islets isolated from patients with hyperinsulinism
    Karen E Cosgrove
    Department of Biomedical Science, Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
    J Clin Endocrinol Metab 87:4860-8. 2002
  6. ncbi Pharmacological characterization of urinary bladder smooth muscle contractility following partial bladder outlet obstruction in pigs
    Ivan Milicic
    Neuroscience Research, Department R4MN, Building AP9, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Eur J Pharmacol 532:107-14. 2006
  7. ncbi SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia-reperfusion injury
    Jean Pierre Bidouard
    Cardiovascular Thrombosis Department, Sanofi Synthelabo Research, 1 Avenue Pierre Brossolette, 91385 Chilly Mazarin Cedex, France
    Eur J Pharmacol 461:49-52. 2003
  8. ncbi Potent inhibition of human leukocyte elastase by 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamide derivatives
    Zhong Lai
    Department of Chemistry, Wichita State University, Wichita, Kansas 67260, USA
    Arch Biochem Biophys 429:191-7. 2004
  9. ncbi Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor
    Zoltan Kapui
    Discovery Research, Sanofi Synthelabo Internal Medicine Budapest Site, Chinoin, Sanofi Synthelabo Group, Budapest, Hungary
    J Pharmacol Exp Ther 305:451-9. 2003
  10. ncbi Highly chiral muscarinic ligands: the discovery of (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonist
    Serena Scapecchi
    Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy
    J Med Chem 49:1925-31. 2006

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Detail Information

Publications113 found, 100 shown here

  1. ncbi Activation of ATP-sensitive K+ channels in the ventromedial hypothalamus amplifies counterregulatory hormone responses to hypoglycemia in normal and recurrently hypoglycemic rats
    Rory J McCrimmon
    Department of Internal Medicine and Endocrinology, Yale University School of Medicine, Section of Endocrinology, P O Box 208020, New Haven, CT 06520 8020, USA
    Diabetes 54:3169-74. 2005
    ..We also conclude that KCOs may offer a future potential therapeutic option for individuals with insulin-treated diabetes who develop defective counterregulation...
  2. ncbi Potent and selective activation of the pancreatic beta-cell type K(ATP) channel by two novel diazoxide analogues
    M Dabrowski
    University Laboratory of Physiology, Parks Road, Oxford, UK
    Diabetologia 46:1375-82. 2003
    ..2/SUR2A), smooth muscle (Kir6.2/SUR2B) and pancreatic beta cell (Kir6.2/SUR1) types of K(ATP) channel...
  3. ncbi The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener, in healthy male subjects
    Milan Zdravkovic
    Novo Nordisk A S, Medical Development, Bagsvaerd, Denmark
    J Clin Pharmacol 45:763-72. 2005
    ..NN414 treatment lowered glucose during the OGTT and 24-hour insulin and glucose levels. In conclusion, a single dose of NN414 is associated with improvements in glucose-related parameters in healthy male subjects...
  4. ncbi [Creation of functional organic compounds and their applications]
    Hiroaki Takayama
    Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, 1091 1 Suarashi, Sagamiko machi, Thukui gun, Kanagawa 199 0195, Japan
    Yakugaku Zasshi 122:127-55. 2002
    ....
  5. ncbi BPDZ 154 activates adenosine 5'-triphosphate-sensitive potassium channels: in vitro studies using rodent insulin-secreting cells and islets isolated from patients with hyperinsulinism
    Karen E Cosgrove
    Department of Biomedical Science, Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
    J Clin Endocrinol Metab 87:4860-8. 2002
    ..These data suggest that BPDZ 154 or BPDZ 154-like compounds may have therapeutic potential in the treatment of certain forms of hyperinsulinism...
  6. ncbi Pharmacological characterization of urinary bladder smooth muscle contractility following partial bladder outlet obstruction in pigs
    Ivan Milicic
    Neuroscience Research, Department R4MN, Building AP9, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Eur J Pharmacol 532:107-14. 2006
    ..K(ATP) channel sensitivities remain essentially unimpaired in the obstructed bladder and could be effectively modulated by openers with potential for the treatment of overactive bladder secondary to outlet obstruction...
  7. ncbi SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia-reperfusion injury
    Jean Pierre Bidouard
    Cardiovascular Thrombosis Department, Sanofi Synthelabo Research, 1 Avenue Pierre Brossolette, 91385 Chilly Mazarin Cedex, France
    Eur J Pharmacol 461:49-52. 2003
    ..05). Subsequent experiments using the latter administration protocol confirmed the ability of SSR69071 (1 and 3 mg/kg i.v.) to reduce infarct size. This cardioprotective activity was associated with inhibition of cardiac elastase...
  8. ncbi Potent inhibition of human leukocyte elastase by 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamide derivatives
    Zhong Lai
    Department of Chemistry, Wichita State University, Wichita, Kansas 67260, USA
    Arch Biochem Biophys 429:191-7. 2004
    ..The results cited herein demonstrate convincingly the superiority of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold over other scaffolds (e.g., saccharin) in the design of inhibitors of (chymo)trypsin-like serine proteases...
  9. ncbi Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor
    Zoltan Kapui
    Discovery Research, Sanofi Synthelabo Internal Medicine Budapest Site, Chinoin, Sanofi Synthelabo Group, Budapest, Hungary
    J Pharmacol Exp Ther 305:451-9. 2003
    ..2 mg/kg) and HLE-induced (ED(30) = 2.7 mg/kg) paw edema in rats after p.o. administration. In conclusion, SSR69071 is a selective, orally active, and potent inhibitor of HLE with good penetration in respiratory tissues...
  10. ncbi Highly chiral muscarinic ligands: the discovery of (2S,2'R,3'S,5'R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonist
    Serena Scapecchi
    Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy
    J Med Chem 49:1925-31. 2006
    ..65, alpha=0.41) while being a poor antagonist on M1, M3, and M4 model tissues (pKb<5)...
  11. ncbi Highly E-selective and effective synthesis of antiarthritic drug candidate S-2474 using quinone methide derivatives
    Masanao Inagaki
    Shionogi Research Laboratories, Shionogi and Company, Ltd, Fukushima ku, Osaka 553 0002, Japan
    J Org Chem 67:125-8. 2002
    ..This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed...
  12. ncbi Short synthesis of tert-butyl-hydroxylated 3,5-di-tert-butyl-4-hydroxybenzaldehyde: Synthesis of tert-butyl-hydroxylated S-2474
    Masanao Inagaki
    Discovery Research Laboratories, Shionogi and Company, Ltd, Fukushima ku, Osaka 553 0002, Japan
    J Org Chem 68:1128-31. 2003
    ..We also accomplished the synthesis of a major metabolite of the antiarthritic drug candidate S-2474...
  13. ncbi 1,2,5-Thiadiazolidin-3-one 1,1-dioxide-based heterocyclic sulfides are potent inhibitors of human tryptase
    Tzutshin Wong
    Department of Chemistry, Wichita State University, Wichita, KS 67260, USA
    Arch Biochem Biophys 436:1-7. 2005
    ..The results described herein demonstrate the versatility of the heterocyclic scaffold in fashioning mechanism-based inhibitors of neutral, basic, and acidic (chymo)trypsin-like serine proteases...
  14. ncbi Potential antidepressant LY 367265 presynaptically inhibits the release of glutamate in rat cerebral cortex
    Su Jane Wang
    School of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan 24205
    Synapse 55:156-63. 2005
    ..Furthermore, the finding that LY 367265 and fluoxetine responses were additive suggests that the simultaneous blockade of 5-HT(2A) receptors and 5-HT uptake transporters might have greater therapeutic efficacy than either action alone...
  15. ncbi Pharmacokinetics of radiolabelled quinlukast in rats
    Matej Syrovatko
    Faculty of Pharmacy, Biophysics and Physical Chemistry, Charles University with the Research Centre, Heyrovskeho 1203, CZ 500 05 Hradec Kralove, Czech Republic
    J Pharm Biomed Anal 38:313-9. 2005
    ..Two hours after intravenous administration, polar metabolites - but no parent drug - were detected in the urine...
  16. ncbi Molecular mobility in glass forming fananserine: a dielectric, NMR, and TMDSC investigation
    L Carpentier
    Laboratoire de Dynamique et Structures des Matériaux Moléculaires, UMR CNRS 8024, ERT 1018, Universite de Lille 1, Batiment P5, 59655, Villeneuve d Ascq Cedex, France
    Pharm Res 23:798-805. 2006
    ..This study was conducted to characterize the molecular mobility of supercooled fananserine and derive from this analysis the non-Arrhenius and nonexponential properties of the primary alpha-relaxation...
  17. ncbi Fluorescence photoswitching of a diarylethene-perylenebisimide dyad based on intramolecular electron transfer
    Tuyoshi Fukaminato
    Research Institute for Electronic Science, Hokkaido University, n20, W10, Kita ku, Sapporo 001 0020, Japan
    Photochem Photobiol Sci 9:181-7. 2010
    ..Femtosecond time-resolved transient and fluorescence lifetime measurements revealed that the fluorescence quenching of the closed-ring isomer is attributed to the intramolecular electron transfer from the PBI chromophore to the DE unit...
  18. ncbi Attenuation of hyperinsulinemia by NN414, a SUR1/Kir6.2 selective K-adenosine triphosphate channel opener, improves glucose tolerance and lipid profile in obese Zucker rats
    Ramin Alemzadeh
    Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
    Metabolism 53:441-7. 2004
    ..These results suggest that pharmacologic attenuation of hyperinsulinemic state by low-dose NN414 may be therapeutically beneficial in insulin-resistant states without any deterioration in overall glycemic control...
  19. ncbi Glutamate agonists for schizophrenia stimulate dopamine D2High receptors
    Philip Seeman
    Schizophr Res 99:373-4. 2008
  20. ncbi S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase A(2)-induced apoptosis
    T Yagami
    Discovery Research Laboratories, Shionogi and Co, Ltd, 12 4, Sagisu 5 Choume, Fukushima ku, Osaka 553 0002, Japan
    Neuropharmacology 49:174-84. 2005
    ..In conclusion, S-2474 exhibits neuroprotective effects against sPLA(2)-IIA. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for stroke via ameliorating neurodegeneration...
  21. ncbi Regioselective synthesis of 6-S-alkyl and 6-S-glycosyl-6-thio-D-mannofuranose derivatives from 5,6-O-cyclic sulfate precursors
    Anne Wadouachi
    Laboratoire des Glucides UMR 6219, Universite de Picardie Jules Verne, 33 rue Saint Leu, F 80039 Amiens, France
    Carbohydr Res 342:1490-5. 2007
    ....
  22. ncbi Applicability of DPI formulations for novel neurokinin receptor antagonist
    M Kumon
    Formulation Technology Research Laboratories, Daiichi Sankyo Co, Ltd, 1 2 58, Hiromachi, Shinagawa ku, Tokyo 140 8710, Japan
    Int J Pharm 356:102-9. 2008
    ..It was concluded that DPI formulation containing mechanofusion-processed lactose could be suitable for inhalation of TNRA...
  23. ncbi Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors
    James A Monn
    Neuroscience Research Division, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    J Med Chem 50:233-40. 2007
    ..Consistent with their mGlu2/3 agonist potency and pharmacokinetic properties, both (+)-11 and (-)-12 blocked phencyclidine-evoked ambulations in a dose-dependent manner, indicating their potential as nonclassical antipsychotic agents...
  24. ncbi Cyclic sulfamidates as versatile lactam precursors. An evaluation of synthetic strategies towards (-)-aphanorphine
    John F Bower
    School of Chemistry, University of Bristol, Bristol, United Kingdom
    Org Biomol Chem 5:143-50. 2007
    ..These approaches were less effective than an aryl radical cyclisation which allowed the completion of a synthesis of in 12 steps from anisaldehyde...
  25. ncbi Stattic: a small-molecule inhibitor of STAT3 activation and dimerization
    Jochen Schust
    Department of Molecular Biology, Independent Research Group, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Chem Biol 13:1235-42. 2006
    ..We propose Stattic as a tool for the inhibition of STAT3 in cell lines or animal tumor models displaying constitutive STAT3 activation...
  26. pmc Regulating RISK: a role for JAK-STAT signaling in postconditioning?
    Michael D Goodman
    Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267, USA
    Am J Physiol Heart Circ Physiol 295:H1649-56. 2008
    ..POC induces myocardial functional protection by activating the RISK pathway. JAK-STAT signaling, however, is insufficient for effective POC without PI3K-Akt activation...
  27. ncbi Synthesis and anti-HIV-1 activity of a novel series of 1,4,2-benzodithiazine-dioxides
    Zdzisław Brzozowski
    Department of Chemical Technology of Drugs, Medical University of Gdansk, 80 416 Gdansk, Poland
    Bioorg Med Chem Lett 16:5298-302. 2006
    ..We successfully identified a lead compound with remarkable anti-HIV-1 activity (EC(50)=0.09microM). These compounds showed minimal cytotoxicity and are therefore suitable for antiviral development...
  28. ncbi Antibacterial oxazolidinones possessing a novel C-5 side chain. (5R)-trans-3-[3-Fluoro-4- (1-oxotetrahydrothiopyran-4-yl)phenyl]-2- oxooxazolidine-5-carboxylic acid amide (PF-00422602), a new lead compound
    Toni Jo Poel
    Michigan Laboratories, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    J Med Chem 50:5886-9. 2007
    ..The title compound (14) showed reduced in vivo myelotoxicity compared to linezolid in a 14-day safety study in rats, potent in vivo efficacy in murine systemic infection models, and excellent pharmacokinetic properties...
  29. ncbi Coupling of liquid chromatography/tandem mass spectrometry and liquid chromatography/solid-phase extraction/NMR techniques for the structural identification of metabolites following in vitro biotransformation of SUR1-selective ATP-sensitive potassium chan
    Florian Gillotin
    Academic Hospital of Liège CHU, Liege, Belgium
    Drug Metab Dispos 38:232-40. 2010
    ..These results greatly help the optimization of the lead compounds...
  30. ncbi Chloro-substituted 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides as ATP-sensitive potassium channel activators: impact of the position of the chlorine atom on the aromatic ring on activity and tissue selectivity
    Bernard Pirotte
    Laboratoire de Chimie Pharmaceutique, Centre Interfacultaire de Recherche du Medicament Drug Research Center, Universite de Liege, 1 Avenue de l Hopital, B 4000 Liege, Belgium
    J Med Chem 53:147-54. 2010
    ..2 K(ATP) channels...
  31. ncbi 1,2-Benzothiazine 1,1-dioxide P(2)-P(3) peptide mimetic aldehyde calpain I inhibitors
    G J Wells
    Department of Medicinal Chemistry, Cephalon, Inc, 145 Brandywine Parkway, West Chester, Pennsylvania 19380-4245, USA
    J Med Chem 44:3488-503. 2001
    ..The achiral unsaturated 1,2-benzothiazine analogues 26a-d are also potent calpain I inhibitors, while 3,4-dihydro-2,1-benzoxathiin (15a,b), 1,2,4-benzothiadiazine (32a,b), and tetrahydroisoquinolinone (36a,b) analogues are less potent...
  32. ncbi Anticancer activity of a cyclooxygenase inhibitor, CX9051, in human prostate cancer cells: the roles of NF-kappaB and crosstalk between the extrinsic and intrinsic apoptotic pathways
    Chiung Hua Huang
    School of Pharmacy, National Taiwan University, No 1, Section 1, Jen Ai Road, Taipei 100, Taiwan
    Naunyn Schmiedebergs Arch Pharmacol 382:159-69. 2010
    ..Taken together, our data suggest that CX9051 induces TRAIL up-regulation and activation of extrinsic apoptotic signaling, which in turn activates mitochondria-mediated intrinsic apoptotic signaling, leading to cancer cell apoptosis...
  33. pmc Effects of structure on inhibitory activity in a series of mechanism-based inhibitors of human neutrophil elastase
    Dengfeng Dou
    Department of Chemistry, Wichita State University, Wichita, KS 67260, United States
    Bioorg Med Chem 18:6646-50. 2010
    ..The results provide a promising framework for the design of highly selective inhibitors of the two enzymes...
  34. ncbi Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231)
    David J O'Neill
    Chemical Sciences, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA
    J Med Chem 53:4511-21. 2010
    ....
  35. ncbi Sulfoxidation with hydrogen peroxide catalyzed by [SeO(4){WO(O(2))(2)}(2)](2-)
    Keigo Kamata
    Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo, 113 8656, Japan
    Dalton Trans 39:5509-18. 2010
    ..The computational investigation supported the high chemoselectivitiy for the sulfoxidation of diallyl sulfide...
  36. ncbi Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model
    Clay L Efferson
    Department of Oncology, Pharmacology, Laboratory of Animal Research, Merck Research Laboratories, Boston, Massachusetts 02115, USA
    Cancer Res 70:2476-84. 2010
    ..These findings suggest that GSI may provide therapeutic benefit to a subset of ERBB2-positive breast cancers and that [(18)F]FDG-PET imaging may be useful in monitoring clinical response...
  37. ncbi LY367265, an inhibitor of the 5-hydroxytryptamine transporter and 5-hydroxytryptamine(2A) receptor antagonist: a comparison with the antidepressant, nefazodone
    I A Pullar
    Eli Lilly and Company, Lilly Research Centre Ltd, Erl Wood Manor, Surrey GU20 6PH, Windlesham, UK
    Eur J Pharmacol 407:39-46. 2000
    ....
  38. ncbi Sulfonylamido derivatives of 2-aminophenoxathiin-10,10-dioxide and related compounds possess antifungal action due to the possible inhibition of lanosterol-14-alpha-demethylase
    C T Supuran
    Universita degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Firenze, Italia
    J Enzyme Inhib 13:291-310. 1998
    ..3-0.5 microgram/mL. Their mechanism of antifungal action is hypothesized to be due to inhibition of lanosterol-14-alpha-demethylase...
  39. ncbi In vitro activity of LY393558, an inhibitor of the 5-hydroxytryptamine transporter with 5-HT(1B/1D/2) receptor antagonist properties
    I A Pullar
    Eli Lilly and Company, Lilly Research Centre Ltd, Erl Wood Manor, Windlesham, GU20 6PH, Surrey, UK
    Eur J Pharmacol 432:9-17. 2001
    ..It is concluded that LY393558 should be an effective antidepressant with the potential to produce an earlier onset of efficacy than selective serotonin uptake inhibitors...
  40. ncbi Structure-activity relationships of norepinephrine reuptake inhibitors with benzothiadiazine dioxide or dihydrosulfostyril cores
    Andrew Fensome
    Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, USA
    Bioorg Med Chem Lett 20:1555-8. 2010
    ..The 3,4-dihydrosulfostyril series was further tested for microsome stability, and compound 16j, which was optimized for both potency and stability, showed efficacy in an in vivo model of thermoregulatory dysfunction...
  41. ncbi [Comparative study of two antitussive drugs in the treatment of acute dry cough of infectious origin (prospective, randomized, single blind study)]
    J C Pujet
    Centre de Diagnostic et de Réadaptation Cardio Respiratoire C T A R, Paris, France
    Therapie 57:457-63. 2002
    ..Moreover, we have observed a tendency towards superior efficacy of T than S. T is therefore a useful alternative in the therapeutic armamentarium available to the general practitioner...
  42. ncbi In vivo regulation of serotonin 5-HT2A receptors in rat brain by subchronic administration of sigma receptor ligand NE-100
    K Hashimoto
    Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry NCNP, Tokyo, Japan
    Life Sci 60:2245-54. 1997
    ..These findings indicate that subchronic treatment with NE-100 may regulate the in vivo binding characteristics of 5-HT2A receptors in the cerebral cortex of rat brain...
  43. ncbi Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV
    Chu Young Kim
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Med Chem 45:888-93. 2002
    ..This study demonstrates how experimental structure determination methods and computational structure prediction methods can be used together to answer questions that cannot be answered by either method alone...
  44. ncbi Persulfoxide: key intermediate in reactions of singlet oxygen with sulfides
    E L Clennan
    Department of Chemistry, University of Wyoming, Laramie, WY 82071, USA
    Acc Chem Res 34:875-84. 2001
    ..Judicious selection of reaction conditions and substituents can allow the use of the persulfoxide as a synthetically useful intermediate...
  45. ncbi Placebo-controlled study of the D4/5-HT2A antagonist fananserin in the treatment of schizophrenia
    P Truffinet
    CNS Department, Rhone Poulenc Rorer Research and Development, Antony, France
    Am J Psychiatry 156:419-25. 1999
    ..The authors' objective was to assess the potential efficacy of fananserin (RP62203), a potent antagonist at the D4 and serotonin2A (5-HT2A) receptors, on symptoms of schizophrenia...
  46. ncbi Ordering and disordering of molecular solids upon mechanical milling: the case of fananserine
    A De Gusseme
    Laboratoire de Dynamique et Structure des Materiaux Moleculaires, UMR CNRS 8024, ERT 1066, Universite des Sciences et Technologies de Lille, F59655 Villeneuve d Ascq, France
    J Pharm Sci 97:5000-12. 2008
    ..The physical stability of the end products is also investigated and discussed with respect to the storage temperature of the material...
  47. pmc 5-tert-Butyl-2-(4'-[18F]fluoropropynylphenyl)-1,3-dithiane oxides: potential new GABA A receptor radioligands
    Xuehe Li
    Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Nucl Med Biol 35:549-59. 2008
    ....
  48. ncbi Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039)
    Matthew J Fell
    Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, DC0510, Indianapolis, IN 46285, USA
    J Pharmacol Exp Ther 326:209-17. 2008
    ....
  49. ncbi Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation
    Peter Grudzien
    Department of Pathology, Loyola University Chicago, Maywood, IL 60153, USA
    Anticancer Res 30:3853-67. 2010
    ..One approach may be targeting signaling pathways, like Notch, that are involved in stem cell self-renewal and survival...
  50. ncbi Novel triple neurokinin receptor antagonist CS-003 strongly inhibits neurokinin related responses
    Hiroshi Tsuchida
    Biological Research Laboratories III, Daiichi Sankyo Co, Ltd, 1 16 13 Kitakasai, Tokyo, 134 8630, Japan
    Eur J Pharmacol 586:306-12. 2008
    ..CS-003 is a potent antagonist of triple neurokinin receptors and may achieve the best therapeutic efficacy on respiratory diseases associated with neurokinins compared to selective neurokinin receptor antagonists...
  51. pmc X-ray snapshot of the mechanism of inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives
    Weijun Huang
    Department of Chemistry, Wichita State University, Wichita, KS 67260, USA
    J Med Chem 51:2003-8. 2008
    ..The identity of the HNE-N-sulfonyl imine species was further corroborated using electrospray ionization mass spectrometry...
  52. ncbi Synthesis and anti-HIV activity evaluation of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo-[4,5-e][1,2]thiadiazines
    Xin Yong Liu
    Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China
    Arch Pharm (Weinheim) 341:216-22. 2008
    ..The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization...
  53. pmc PYRROLO[1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) induce apoptosis in K562 cells
    Gabriella Marfe
    Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy
    BMC Cancer 7:207. 2007
    ..The objective of this study was to gain insight into the molecular mechanism of induced cell death (apoptosis) by PYRROLO [1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) series compounds, using human (K562) cells as a model...
  54. ncbi Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor
    Gabriel Mbalaviele
    Pfizer Inc, Chesterfield, MO 63017, USA
    Biochem Pharmacol 79:1445-54. 2010
    ..This profile of mPGES-1 inhibition, distinct from COX-2 inhibition in cells, validates mPGES-1 as an attractive target for therapeutic intervention...
  55. pmc Unphosphorylated STAT3 modulates alpha 7 nicotinic receptor signaling and cytokine production in sepsis
    Geber Peña
    Laboratory of Immunity and Infection, Department of Surgery, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Eur J Immunol 40:2580-9. 2010
    ..Stattic also prevented the production of late mediators of sepsis and improved survival in established sepsis. These results reveal the immunological implications of tyrosine-unphosphorylated STAT3 in infectious diseases...
  56. ncbi The vibrational spectra of 1,3-dithiane-1-oxide and 1,3-dithia-1-oxocyclohept-5-ene
    A I Noskov
    Kazan State University, Kremlevskaya str 18, Kazan 420008, Russia
    Spectrochim Acta A Mol Biomol Spectrosc 77:6-10. 2010
    ..Vibrational frequencies for both conformations (I) and (II) were calculated. After appropriate scaling a reasonably good agreement between the experimental and calculated wave numbers was obtained...
  57. ncbi Selective inducible microsomal prostaglandin E(2) synthase-1 (mPGES-1) inhibitors derived from an oxicam template
    Jane Wang
    Pfizer Inc St Louis Laboratory, PGRD Research, 700 Chesterfield Pkwy W, Chesterfield, MO 63017, USA
    Bioorg Med Chem Lett 20:1604-9. 2010
    ..In addition, it displayed PGE(2) inhibition in a cell-based assay (0.42microM) and had over 238-fold selectivity for mPGES-1 over COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF(1alpha)...
  58. ncbi In vivo effects of a combined 5-HT1B receptor/SERT antagonist in experimental pulmonary hypertension
    Ian Morecroft
    FBLS, University of Glasgow, Glasgow G12 8QQ, UK
    Cardiovasc Res 85:593-603. 2010
    ....
  59. ncbi Imidazo-pyrazine derivatives as potent CXCR3 antagonists
    Xiaohui Du
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 19:5200-4. 2009
    ..The efficacy of the lead compound 21 is evaluated in a mouse lung inflammation model...
  60. ncbi High-throughput approaches towards the definitive identification of pharmaceutical drug metabolites. 2. An example of how unexpected dissociation behaviour could preclude correct assignment of sites of metabolism
    Stephen W Holman
    School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK
    Rapid Commun Mass Spectrom 23:2017-25. 2009
    ..The planar structures of the posited product ions are likely to provide the driving force for the rearrangements. The relevance of the observations with regards to pharmaceutical drug metabolite identification is discussed...
  61. ncbi Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells
    Sudhir S Rao
    Merck Research Laboratories, Boston, Massachusetts 02115, USA
    Cancer Res 69:3060-8. 2009
    ....
  62. ncbi STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria
    Lobelia Samavati
    Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Mol Immunol 46:1867-77. 2009
    ..This inhibition did not affect caspase-1 activation. These results highlight the complex role of STAT3 in cytokine production and the key role of STAT3 tyrosine phosphorylation in IL-1beta and IL-6 production in response to inflammation...
  63. pmc Targeting the Notch1 and mTOR pathways in a mouse T-ALL model
    Kathleen Cullion
    Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Blood 113:6172-81. 2009
    ..This work supports the idea of targeting NOTCH1 in T-ALL and suggests that inhibition of the mTOR and NOTCH1 pathways may have added efficacy...
  64. ncbi Signal transducer and activator of transcription 3 (STAT3) regulates adipocyte differentiation via peroxisome-proliferator-activated receptor gamma (PPARgamma)
    Dongmei Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China
    Biol Cell 102:1-12. 2010
    ..However, no direct evidence for a role of STAT3 in 3T3-L1 adipocyte differentiation has been reported...
  65. ncbi Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1)
    Yurong Lai
    Departments of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Pfizer Inc, St Louis, Missouri, USA
    J Pharmacol Exp Ther 334:936-44. 2010
    ....
  66. pmc Inhibition of gamma-secretase activity inhibits tumor progression in a mouse model of pancreatic ductal adenocarcinoma
    Ruben Plentz
    Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA
    Gastroenterology 136:1741-9.e6. 2009
    ..We investigated the role of this pathway in PDAC progression...
  67. ncbi Two enantiomerically pure cyclic arenesulfonamide hydrochloride salts
    Lionel Kiefer
    Institut de Chimie des Substances Naturelles, UPR 2301, Centre National de la Recherche Scientifique, Bâtiment 27, 1 Avenue de la Terrasse, F 91198 Gif sur Yvette, France
    Acta Crystallogr C 65:o46-50. 2009
    ..The connectivities between molecules in the crystal structures are also different, but both involve hydrogen bonding mediated by chloride ions as a common dominant feature...
  68. ncbi LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY-404039 for the potential treatment of schizophrenia
    Mario Mezler
    Abbott Laboratories, Global Pharmaceutical Research and Development, Neuroscience Clinical Development, Abbott Park, IL 60064 6075, USA
    Curr Opin Investig Drugs 11:833-45. 2010
    ..Thus, LY-2140023 represents a rare psychiatric medicine that demonstrates the promise of being rationally developed from bench to bedside...
  69. ncbi Keto-enol tautomerism in crystals of 3-[hydroxy(phenyl)methyl]-2,5,7-trimethyl-2,3-dihydropyrido[3,2-e][1,2]thiazin-4-one 1,1-dioxide and 3-(1-hydroxyethylidene)-2,5,7-trimethyl-2,3-dihydropyrido[3,2-e][1,2]thiazin-4-one 1,1-dioxide
    Zbigniew Karczmarzyk
    Department of Chemistry, University of Podlasie, ul 3 Maja 54, 08 110 Siedlce, Poland
    Acta Crystallogr C 64:o590-4. 2008
    ..O hydrogen bonding and C-H...pi interactions. In the crystal structure of (II), the molecules are linked by a combination of O-H...O hydrogen bonding and C-H...pi and pi-pi interactions...
  70. pmc Strategic design of an effective beta-lactamase inhibitor: LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone
    Priyaranjan Pattanaik
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 284:945-53. 2009
    ..The 2'-substituted penicillin sulfone, LN-1-255, is proving to be an important lead compound for novel beta-lactamase inhibitor design...
  71. ncbi 3-Alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to diazoxide and pinacidil as potassium channel openers acting on vascular smooth muscle cells: design, synthesis, and pharmacological evaluation
    B Pirotte
    Laboratoire de Chimie Pharmaceutique, Universite de Liege, 1, Avenue de l Hopital, CHU, Tour 4, B 4000 Liege, Belgium
    J Med Chem 43:1456-66. 2000
    ....
  72. ncbi Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassiu
    Kathrin Maedler
    Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, CH 8091 Zurich, Switzerland
    Diabetes 53:1706-13. 2004
    ..Thus, in human islets, glucose- and IL-1beta-induced beta-cell secretory dysfunction and apoptosis are Ca(2+) influx and ERK dependent and can be prevented by the beta-cell selective potassium channel opener NN414...
  73. ncbi Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)
    William A Carroll
    Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064 6101, USA
    J Med Chem 47:3163-79. 2004
    ..Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective K(ATP) channel openers may have utility in the treatment of overactive bladder...
  74. ncbi Improved beta-cell survival and reduced insulitis in a type 1 diabetic rat model after treatment with a beta-cell-selective K(ATP) channel opener
    Kresten Skak
    Department of Pharmacology, Novo Nordisk A S, Måløv, Denmark
    Diabetes 53:1089-95. 2004
    ..Thus, this study demonstrated that treatment with KCO compounds can indeed lead to preservation of beta-cell function and reduction of insulitis in a rat diabetes model...
  75. ncbi Induction of beta-cell rest by a Kir6.2/SUR1-selective K(ATP)-channel opener preserves beta-cell insulin stores and insulin secretion in human islets cultured at high (11 mM) glucose
    Robert A Ritzel
    Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Clin Endocrinol Metab 89:795-805. 2004
    ..Impaired glucose-regulated insulin secretion in TTDM may, however, partially involve mechanisms that are distinct from insulin stores and insulin secretion rates...
  76. ncbi NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat
    Richard D Carr
    Department of Pharmacological Research I, Novo Nordisk, Bagsvaerd, Denmark
    Diabetes 52:2513-8. 2003
    ..NN414 may therefore represent a novel approach to the prevention and treatment of impaired glucose tolerance and type 2 diabetes...
  77. ncbi [Studies on the new antiarthritic drug candidate S-2474]
    Masanao Inagaki
    Discovery Research Laboratories, Shionogi and Company, Ltd, 12 4, Sagisu 5 Chome, Fukushima ku, Osaka 553 0002, Japan
    Yakugaku Zasshi 123:323-30. 2003
    ..This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed...
  78. ncbi A novel orally active inhibitor of HLE
    Marton Varga
    Chinoin Co Ltd Member of Sanofi Synthelabo Group, Discovery Research, H 1045, Tó utca 1 5, Budapest, Hungary
    Eur J Med Chem 38:421-5. 2003
    ..Pharm. Exp. Ther., submitted for publication)...
  79. ncbi Synthesis and activities of oxidative metabolites of the anti-arthritic drug candidate S-2474
    Masanao Inagaki
    Discovery Research Laboratories, Shionogi and Co, Ltd, Fukushima ku, 553 0002, Osaka, Japan
    Bioorg Med Chem 11:2415-9. 2003
    ..In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay...
  80. ncbi Oxathiolene oxides: a novel family of compounds that induce ferritin, glutathione S-transferase, and other proteins of the phase II response
    E Christine Pietsch
    Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, NC 27157, USA
    Biochem Pharmacol 65:1261-9. 2003
    ..Consistent with this observation, OTEO-562 failed to induce cytochrome P450 1A1 mRNA. These results suggest that oxathiolene oxides may merit further investigation as candidate chemopreventive agents...
  81. ncbi K-ATP opener-mediated attenuation of spontaneous bladder contractions in ligature-intact, partial bladder outlet obstructed rats
    James J Lynch
    Neuroscience Research, Global Pharmaceutical Research and Development, Department R4N5, Bldg AP9A LL, Abbott Laboratories, 100 Abbott Park Road, IL 60064 6115, USA
    Life Sci 72:1931-41. 2003
    ....
  82. ncbi (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. II. in vivo characterization
    Michael E Brune
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Illinois 60064, USA
    J Pharmacol Exp Ther 303:387-94. 2002
    ....
  83. ncbi (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. I. In vitro characterization
    Murali Gopalakrishnan
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Illinois 60064, USA
    J Pharmacol Exp Ther 303:379-86. 2002
    ..The pharmacological profile of A-278637 represents an attractive basis for further investigations of selective K(ATP) channel openers for the treatment of overactive bladder via myogenic etiology...
  84. ncbi Synthesis and pharmacological profile of 6-methyl-3-isopropyl-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide derivatives: non-steroidal anti-inflammatory agents with reduced ulcerogenic effects in the rat
    Yakdhane Kacem
    Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Faculte des Sciences, Avenue de l Environnement, 5000, Monastir, Tunisia
    Eur J Pharm Sci 16:221-8. 2002
    ..5 mg/kg, i.p.). Comparison of the gastrointestinal safety of compounds 6a-f with that of piroxicam showed a far better tolerability for our products. This comparison was based on the ulcer index and the pH of gastric content...
  85. ncbi [Thermodynamics of drug polymorphism: domains and stability hierarchy by pressure temperature diagram. Application to the tetramorphism of fananserine]
    S Toscani
    Laboratoire de Chimie Physique et de Chimie Minérale, Faculte des Sciences Pharmaceutiques et Biologiques, Universite Rene Descartes Paris V, 4, avenue de l Observatoire, F75006 Paris, France
    Ann Pharm Fr 60:203-11. 2002
    ..Conversely, phase I is overall metastable and exhibits a whole monotropic behaviour...
  86. ncbi RP 62203, a 5-hydroxytryptamine2 antagonist, enhances deep NREM sleep in rats
    J M Stutzmann
    Electrophysiology Department, Rhone Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France
    Sleep 15:119-24. 1992
    ..RP 62203 could therefore be of clinical interest in the management of sleep disorders, particularly those developing within a psychiatric context...
  87. ncbi LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat
    S N Mitchell
    Eli Lilly and Company Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
    Eur J Pharmacol 432:19-27. 2001
    ..Its neurochemical profile in vivo suggests that it may be a more effective antidepressant with the potential for producing an earlier onset of clinical activity than selective serotonin reuptake inhibitors...
  88. ncbi 1,2,5-Thiadiazolidin-3-one 1,1 dioxide: a powerful scaffold for probing the S' subsites of (chymo)trypsin-like serine proteases
    W C Groutas
    Department of Chemistry, Wichita State University, Kansas 67260, USA
    Arch Biochem Biophys 385:162-9. 2001
    ..Several of the compounds were found to be highly potent and selective time-dependent inhibitors of HLE, PR 3, and Cat G...
  89. ncbi (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a novel ATP-sensitive potassium channel opener: hemodynamic comparison to ZD-6169, WAY-133537, and nifedipine in the anesthetized canine
    Ryan M Fryer
    Integrative Pharmacology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064 6119, USA
    J Cardiovasc Pharmacol 44:137-47. 2004
    ..These data suggest that A-278637 possesses a greater functional selectivity for urinary bladder versus vascular smooth muscle in vivo and that A-278637 may exhibit a more favorable therapeutic index than either ZD-6169 or WAY-133537...
  90. ncbi Extractive spectrophotometric methods for the determination of oxomemazine hydrochloride in bulk and pharmaceutical formulations using bromocresol green, bromocresol purple and bromophenol blue
    Akram M El-Didamony
    Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt
    Arch Pharm (Weinheim) 338:190-7. 2005
    ..No interference was observed from common pharmaceutical excipients. Statistical comparison of the results with those obtained by HPLC method shows excellent agreement and indicates no significant difference in accuracy and precision...
  91. ncbi 3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides as ATP-sensitive potassium channel openers: effect of 6,7-disubstitution on potency and tissue selectivity
    Pascal de Tullio
    Centre de recherche en Pharmacochimie des Substances Naturelles et Synthétiques, Laboratoire de Chimie Pharmaceutique, Universite de Liege, 1 Avenue de l Hopital, B 4000 Liege, Belgium
    J Med Chem 48:4990-5000. 2005
    ..34 was found to be one of the most potent and selective pancreatic potassium channel openers yet described...
  92. ncbi Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers
    Jun Konishi
    Division of Hematology and Medical Oncology and Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Cancer Res 67:8051-7. 2007
    ..In conclusion, these results support the hypothesis that inhibition of Notch activation using a gamma-secretase inhibitor represents a potential new approach for the targeted therapy of lung cancer...
  93. ncbi Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial
    Sandeep T Patil
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Nat Med 13:1102-7. 2007
    ..These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia...
  94. ncbi Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors
    Pierre Francotte
    Drug Research Center, Laboratoire de Chimie Pharmaceutique, Universite de Liege, Av de l Hôpital, 1, B36, 4000 Liege, Belgium
    J Med Chem 50:3153-7. 2007
    ..The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration...
  95. ncbi A new type of mixed anhydride and its applications to the synthesis of 7-substituted 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazines with in vitro antitumor activity
    Zdzisław Brzozowski
    Department of Chemical Technology of Drugs, Medical University of Gdansk, 80 416 Gdansk, Poland
    J Med Chem 45:430-7. 2002
    ..The prominent compound with remarkable activity (log GI(50) < -8) and selectivity for the leukemia HL-60(TB) cell line was 2-methyl-8-quinolyl 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine-7-carboxylate 24...
  96. ncbi In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonist LY404039 in animal models of psychiatric disorders
    Linda M Rorick-Kehn
    Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, DC0510, Indianapolis, IN 46285, USA
    Psychopharmacology (Berl) 193:121-36. 2007
    ....
  97. ncbi Ring expansion reactions of 4-amino-1,1-dioxo-[1,2,3,5]-thiatriazoles
    Peter J Duggan
    CSIRO Molecular and Health Technologies, Bag 10, Clayton South, Victoria 3169, Australia
    Org Biomol Chem 5:472-7. 2007
    ..The reaction of with phenacyl bromides or a phenacyl dibromide forms fully unsaturated 5-amino-1,1-dioxo-[1,2,4,6]-thiatriazines...
  98. ncbi Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid
    Linda M Rorick-Kehn
    Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, DC0510, Indianapolis, IN 46285, USA
    J Pharmacol Exp Ther 321:308-17. 2007
    ..Collectively, the current data indicate that LY404039 may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis...
  99. ncbi Three-dimensional quantitative structure-activity relationships of ATP-sensitive potassium (KATP) channel openers belonging to the 3-alkylamino-4H-1,2,4-benzo- and 3-alkylamino-4H-1,2,4-pyridothiadiazine 1,1-dioxide families
    Pascal de Tullio
    Centre de recherche en Pharmacochimie des Substances Naturelles et Synthétiques, Laboratoire de Chimie Pharmaceutique, Universite de Liege, 1 Avenue de l Hopital, B 4000 Liege, Belgium
    J Med Chem 49:6779-88. 2006
    ..Moreover, an original CoMSIA analysis, using a selectivity index (SI) as a dependent variable, was also performed with the aim of identifying the structural parameters influencing tissue selectivity...
  100. ncbi A new small-molecule Stat3 inhibitor
    John S McMurray
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 36, Houston, Texas 77030, USA
    Chem Biol 13:1123-4. 2006
    ..Stattic is a new tool for studying Stat3 signaling and demonstrates that the SH2 domain is not a dead target...
  101. ncbi Identification of new compounds that trigger apoptosome-independent caspase activation and apoptosis
    Emanuela Aleo
    Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia and MATI Center of Excellence, Universita di Udine, Udine, Italy
    Cancer Res 66:9235-44. 2006
    ....

Research Grants1

  1. Role of AMPK in hypoglycemia-sensing in the ventromedial hypothalamus
    RORY MCCRIMMON; Fiscal Year: 2008
    ..Finally, the proposal aims to obtain data that will support the hypothesis that recurrent hypoglycemia induces mitochondrial biogenesis in the VMH, an effect that may be mediated by AMPK. ..