- Discovery and optimization of a novel series of N-arylamide oxadiazoles as potent, highly selective and orally bioavailable cannabinoid receptor 2 (CB2) agonists
Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320, USA
J Med Chem 51:5019-34. 2008
..This effort resulted in identification of 63 that is a potent and selective agonist at CB2 (EC50 = 2 nM, Emax = 110%) with excellent pharmacokinetic properties...
- PTC124 targets genetic disorders caused by nonsense mutations
Ellen M Welch
PTC Therapeutics, 100 Corporate Court, South Plainfield, New Jersey 07080, USA
Nature 447:87-91. 2007
- [1,2,4]triazol-3-ylsulfanylmethyl)-3-phenyl-[1,2,4]oxadiazoles: antagonists of the Wnt pathway that inhibit tankyrases 1 and 2 via novel adenosine pocket binding
Michael D Shultz
Novartis Institutes for BioMedical Research, Inc, Cambridge, Massachusetts 02319, United States
J Med Chem 55:1127-36. 2012
..Furthermore, a cocrystal structure of compound 24 complexed to TNKS1 demonstrates an alternate binding mode for PARP family member proteins that does not involve interactions with the nicotinamide binding pocket...
- PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model
Department of Microbiology and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Proc Natl Acad Sci U S A 105:2064-9. 2008
- PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation
Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, PA, USA
J Inherit Metab Dis 34:443-7. 2011
..Our results provide additional evidence for proof of principle that PTC124 is a potential therapeutic agent for treating patients with any genetic condition that results from a nonsense mutation...
- Identification of oxadiazoles as new drug leads for the control of schistosomiasis
Ahmed A Sayed
Department of Biological Sciences, Illinois State University, Normal, Illinois 61790, USA
Nat Med 14:407-12. 2008
..The compound was active against the three major schistosome species infecting humans. These protective effects exceed benchmark activity criteria set by the World Health Organization for lead compound development for schistosomiasis...
- Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers
PTC Therapeutics, Inc, 100 Corporate Court, South Plainfield, NJ 07080, USA
J Clin Pharmacol 47:430-44. 2007
..PTC124 pharmacokinetics were described by a 1-compartment model. Collectively, the data support initiation of phase II studies of PTC124 in patients with nonsense mutation-mediated cystic fibrosis and Duchenne muscular dystrophy...
- PTC124-mediated translational readthrough of a nonsense mutation causing Usher syndrome type 1C
Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University Mainz, D 55099 Mainz, Germany
Hum Gene Ther 22:537-47. 2011
..Its high readthrough efficiency in combination with excellent biocompatibility makes PTC124 a promising therapeutic agent for PTCs in USH1C, as well as other ocular and nonocular genetic diseases...
- Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring
Section of Clinical Pharmacology and Hypertension, Virginia Commonwealth University, Richmond, VA 23298 0160, USA
J Clin Hypertens (Greenwich) 13:467-72. 2011
..These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class...
- Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial
Hadassah Hebrew University Hospital, Jerusalem, Israel
Lancet 372:719-27. 2008
..PTC124 is an orally bioavailable small molecule that is designed to induce ribosomes to selectively read through premature stop codons during mRNA translation, to produce functional CFTR...
- Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis
Paediatric Gastroenterology, Hadassah University Hospital, Mount Scopus POB 24035, Jerusalem, 91240, Israel
Eur Respir J 38:59-69. 2011
..Adverse clinical and laboratory findings were uncommon and usually mild. Chronic ataluren administration produced time-dependent improvements in CFTR activity and clinical parameters with generally good tolerability...
- A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like Peptide-1 and glucose-dependent insulinotropic Peptide release
Zhi Liang Chu
Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, California 92121, USA
Endocrinology 149:2038-47. 2008
..These data also suggest that combined stimulation of incretin hormone release and protection against incretin hormone degradation may be an effective antidiabetic strategy...
- Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension
William B White
Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030 3940, USA
Hypertension 57:413-20. 2011
..Azilsartan medoxomil could provide higher rates of hypertension control within the ARB class...
- Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles
Adnan A Kadi
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Eur J Med Chem 42:235-42. 2007
..derivatives 3a-j, which were cyclized to the corresponding 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles 4a-j via heating with phosphorus oxychloride...
- A role for beta-cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucose-dependent insulin release
Zhi Liang Chu
Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA
Endocrinology 148:2601-9. 2007
..Diabetic KK/A(y) mice were also highly responsive to AR231453. Orally active GPR119 agonists may offer significant promise as novel antihyperglycemic agents acting in a glucose-dependent fashion...
- Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Hum Mol Genet 21:4007-20. 2012
..These studies establish the therapeutic potential of RTC13 in vivo and advance this newly identified compound into preclinical application for DMD...
- Molecular and cellular effects of azilsartan: a new generation angiotensin II receptor blocker
Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan
J Hypertens 29:2476-83. 2011
..Although azilsartan is considered to be an unusually potent angiotensin II type 1 (AT1) receptor antagonist, little is known about the potential pleiotropic effects of this molecule...
- In vitro antagonistic properties of a new angiotensin type 1 receptor blocker, azilsartan, in receptor binding and function studies
Pharmacology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd, Osaka, Japan
J Pharmacol Exp Ther 336:801-8. 2011
..Its tight receptor binding might be expected to produce potent and long-lasting antihypertensive effects in preclinical and clinical settings...
- Multiple independent binding sites for small-molecule inhibitors on the oncoprotein c-Myc
Dalia I Hammoudeh
Department of Chemistry, Georgetown University, Washington, District of Columbia 20057, USA
J Am Chem Soc 131:7390-401. 2009
..A rational and generic approach to the inhibition of protein-protein interactions involving ID proteins may therefore be possible through the targeting of ID sequence...
- The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure
George L Bakris
Hypertensive Diseases Unit, University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA
J Clin Hypertens (Greenwich) 13:81-8. 2011
..0 to -0.1; P=.038), while AZL-M 40 mg was noninferior to OLM-M 40 mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M...
- Introducing sense into nonsense in treatments of human genetic diseases
Department of Genetics, The Life Sciences Institute, Givat Ram Campus, The Hebrew University, Jerusalem 91904, Israel
Trends Genet 24:552-63. 2008
..A deeper understanding of the molecular basis for variable response to readthrough of PTCs is necessary so that appropriate therapies can be developed to treat many human genetic diseases caused by PTCs...
- Differential pharmacology and benefit/risk of azilsartan compared to other sartans
Theodore W Kurtz
Department of Laboratory Medicine, University of California, San Francisco, CA 94107, USA
Vasc Health Risk Manag 8:133-43. 2012
- Oxadiazoles in medicinal chemistry
AstraZeneca R and D Molndal, S 431 83 Molndal, Sweden
J Med Chem 55:1817-30. 2012
b>Oxadiazoles are five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom, and they exist in different regioisomeric forms...
- Synthesis, crystal structure and anti-HIV activity of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles
Mahmood Ul Hassan Khan
Department of Chemistry, Quaid i Azam University, Islamabad 45320, Pakistan
Med Chem 8:1190-7. 2012
Two series of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles (4a-l and 5a-l) were synthesized by cyclodehydration of adamantan-1-carboxylic acid/adamantylacetic acid with various aryl hydrazides (3a-l) in the presence of POCl(3)...
- Pharmacophore identification of c-Myc inhibitor 10074-G5
Jeremy L Yap
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine St, Baltimore, MD 21201, USA
Bioorg Med Chem Lett 23:370-4. 2013
..Importantly, the carboxylic acid of JY-3-094 improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance Myc inhibitory activity further still...
- Antibacterial activity of chalcones, hydrazones and oxadiazoles against methicillin-resistant Staphylococcus aureus
Thaís Moreira Osório
Laboratório de Antibióticos, Universidade Federal de Santa Catarina UFSC, Campus Trindade, CEP 88040 900 Florianópolis, SC, Brazil
Bioorg Med Chem Lett 22:225-30. 2012
..In this context, chalcones, dihydrochalcones, hydrazones and oxadiazoles were tested against Staphylococcus aureus ATCC 25923 and methicillin-resistant S...
- Ataluren as an agent for therapeutic nonsense suppression
Stuart W Peltz
PTC Therapeutics, Inc, South Plainfield, New Jersey 07080, USA
Annu Rev Med 64:407-25. 2013
- Membrane blebbing as an assessment of functional rescue of dysferlin-deficient human myotubes via nonsense suppression
University of Pennsylvania School of Medicine, Department of Physiology, B400 Richards Bldg, 3700 Hamilton Walk, Philadelphia, PA 19104 6085, USA
J Appl Physiol (1985) 109:901-5. 2010
..Thus ataluren is a potential therapeutic for dysferlin-deficient patients harboring nonsense mutations...
- Synthesis, antimicrobial and cytotoxic activities of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India
Eur J Med Chem 44:2106-12. 2009
A new class of 1,3,4-oxadiazoles were prepared from acid hydrazides on treatment with different carboxylic acids in the presence of phosphorus oxychloride...
- Azilsartan medoxomil: a new Angiotensin receptor blocker
Massachusetts College of Pharmacy and Health Sciences and Harvard Vanguard Medical Associates, Boston, MA, USA
Clin Ther 33:1577-89. 2011
..Azilsartan medoxomil is an angiotensin receptor blocker, approved on February 25, 2011 by the US Food and Drug Administration (FDA) for hypertension management...
- Synthesis and antifungal activity of novel sulfoxide derivatives containing trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety
Center for Research and Development of Fine Chemicals, Key Laboratory of Green Pesticide and Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China
Bioorg Med Chem 16:3632-40. 2008
..After treating with compound 10a at 100 microg/mL for 12 h, the mycelial reducing sugar, D-GlcNAc, soluble protein and pyruvate content, chitinase activity showed declining tendency...
- In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization
Dana M Clausen
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA
J Pharmacol Exp Ther 335:715-27. 2010
..Our identification of 10074-G5 metabolites in mice will help design new, more metabolically stable small-molecule inhibitors of c-Myc...
- Synthesis and evaluation of a series of 2-substituted-5-thiopropylpiperazine (piperidine)-1,3,4-oxadiazoles derivatives as atypical antipsychotics
Department of Systems Biology, Huazhong University of Science and Technology, Wuhan, China
PLoS ONE 7:e35186. 2012
- AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines
Dana S Levy
Oncology Biology, GlaxoSmithKline, Collegeville, PA 19426, USA
Blood 113:1723-9. 2009
..Overall, our data provide direct evidence for the role of AKT signaling in various hematologic malignancies, especially ALL and some lymphomas...
- Synthesis of novel sulfonamide-1,2,4-triazoles, 1,3,4-thiadiazoles and 1,3,4-oxadiazoles, as potential antibacterial and antifungal agents. Biological evaluation and conformational analysis studies
Laboratory of Molecular Analysis, Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas Constantinou Ave, 11635 Athens, Greece
Bioorg Med Chem 20:1569-83. 2012
..we designed the synthesis of a series of novel sulfonamide-1,2,4-triazoles, -1,3,4-thiadiazoles and -1,3,4-oxadiazoles emphasizing, in particular, on the strategy of combining two chemically different but pharmacologically ..
- Read-through strategies for suppression of nonsense mutations in Duchenne/ Becker muscular dystrophy: aminoglycosides and ataluren (PTC124)
Richard S Finkel
Division of Neurology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
J Child Neurol 25:1158-64. 2010
..Use of nonsense mutation suppression in Duchenne/Becker muscular dystrophy may offer the prospect of targeting the specific mutation causing the disease and correcting the fundamental pathophysiology...
- Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents
Jaiprakash N Sangshetti
Department of Chemical Technology, Dr Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, MS, India
Bioorg Med Chem Lett 21:444-8. 2011
..Some of the compounds from the series like 8k was equipotent with miconazole against Candida albicans and Fusarium oxysporum. Also compound 8n was equipotent with miconazole against F. oxysporum...
- Rescue of melanocortin 4 receptor (MC4R) nonsense mutations by aminoglycoside-mediated read-through
Institute of Experimental Pediatric Endocrinology, Charite Universitatsmedizin Berlin, Berlin, Germany
Obesity (Silver Spring) 20:1074-81. 2012
..Restoration of full-length proteins by PTC124 could not be confirmed. Future pharmaceutical applications must consider the potency of aminoglycosides to restore receptor function as well as the ability to pass the blood-brain barrier...
- The chemical compound PTC124 does not affect cellular electrophysiology of cardiac ventricular myocytes
Tamara T Koopmann
Heart Failure Research Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands
Cardiovasc Drugs Ther 26:41-5. 2012
..In this study, we tested the acute and long-term effects of PTC124 on action potential characteristics of rabbit ventricular cardiomyocytes...
- Discovery and structure-activity relationship of 3-aryl-5-aryl-1,2,4-oxadiazoles as a new series of apoptosis inducers and potential anticancer agents
Han Zhong Zhang
Maxim Pharmaceuticals Inc, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA
J Med Chem 48:5215-23. 2005
..Therefore, our cell-based chemical genetics approach for the discovery of apoptosis inducers can identify potential anticancer agents as well as their molecular targets...
- Ultrasound-promoted synthesis of 3-trichloromethyl-5-alkyl(aryl)-1,2,4-oxadiazoles
Lizandra C Bretanha
NuQuiA Núcleo de Química Aplicada, Departamento de Quimica Organica, Universidade Federal de Pelotas, Brazil
Ultrason Sonochem 18:704-7. 2011
The alternative synthesis of 12 1,2,4-oxadiazoles using ultrasound irradiation from trichloroacetoamidoxime and acyl chlorides is reported. Seven of them are novel compounds...
- Development of an HPLC-fluorescence determination method for carboxylic acids related to the tricarboxylic acid cycle as a metabolome tool
Laboratory of Bio Analytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
Biomed Chromatogr 19:788-95. 2005
..The method will also be useful for metabolome research, such as for target analyses of metabolites with carboxyl groups, not only in urine but also in cells and organs...
- Distinct molecular requirements for activation or stabilization of soluble guanylyl cyclase upon haem oxidation-induced degradation
L S Hoffmann
Pharma Research Centre, Bayer HealthCare, Aprather Weg 18a, Wuppertal, Germany
Br J Pharmacol 157:781-95. 2009
- A fluorogenic reagent, 4-mercapto-7-methylthio-2,1,3-benzoxadiazole for carboxylic acids, designed by prediction of the fluorescence intensity
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan
Anal Chem 73:2165-70. 2001
..The superiority was examined in terms of its reactivity and sensitivity and the avoidance of interfering peaks that were derived from the reagent itself or degradation products in the chromatogram...
- 2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors
IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600 Pomezia, 00040 Rome, Italy
Bioorg Med Chem Lett 18:6083-7. 2008
..Exploration of replacements for the carboxamide with bioisosteric pentatomic heteroaromatic like 1,3,4-oxadiazoles, 1,2,4-oxadiazoles and 1,3-thiazoles, led to the discovery that 2-trifluoroacetylthiophene 1,3,4-oxadiazole ..
- Novel 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives: promising anticancer agents
Ahmed S Aboraia
Pharmaceutical Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Egypt
Bioorg Med Chem 14:1236-46. 2006
..Compounds 3j and 3k proved to be the active members in this study compared to 5-fluorouracil and cyclophosphamide as reference drugs, respectively. Compounds 3j and 3k were identified as promising lead compounds...
- The molecular mechanism of human hormone-sensitive lipase inhibition by substituted 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones
Yassine Ben Ali
Organization and Dynamics of Biological Membranes, UMR 5246 ICBMS, CNRS Universite Claude Bernard Lyon 1, Batiment Raulin, 43, Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
Biochimie 94:137-45. 2012
..On the basis of this study, a kinetic model is proposed to describe the inhibition of HSL by compound 7600 in the aqueous phase as well as its partial reactivation at the lipid-water interface...
- In vivo electrophysiological assessment of the putative antidepressant Wf-516 in the rat raphe dorsalis, locus coeruleus and hippocampus
M el Mansari
University of Ottawa Institute of Mental Health Research, Room 7407, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada
Naunyn Schmiedebergs Arch Pharmacol 376:351-61. 2008
..These properties of WF-516 define the transporter/receptorial profile of an antidepressant with superior effectiveness...
- Kinetics of novel competitive inhibitors of urease enzymes by a focused library of oxadiazoles/thiadiazoles and triazoles
International Center for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan
Biochem Biophys Res Commun 319:1053-63. 2004
..Because of their safe profile in the genotoxic assay, they may be pursued in the near future for human testing..
- 2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors
Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495 009, CG, India
Bioorg Med Chem Lett 21:5735-8. 2011
..The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor...
- Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis
NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, Maryland 20892 3370, USA
J Med Chem 52:6474-83. 2009
..The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents...
- Azilsartan medoxomil: a new angiotensin II receptor antagonist for treatment of hypertension
William L Baker
School of Pharmacy, University of Connecticut, Farmington, CT, USA
Ann Pharmacother 45:1506-15. 2011
- Selective, reversible caspase-3 inhibitor is neuroprotective and reveals distinct pathways of cell death after neonatal hypoxic-ischemic brain injury
Byung Hee Han
Department of Neurology, Washington University, St Louis, Missouri 63110, USA
J Biol Chem 277:30128-36. 2002
- Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression
Douglas S Auld
NIH Chemical Genomics Center, National Institutes of Health, Bethesda, MD 20892 3370, USA
Proc Natl Acad Sci U S A 106:3585-90. 2009
..Our results demonstrate the value of understanding potential interactions between reporter enzymes and chemical compounds and emphasize the importance of implementing the appropriate control assays before interpreting HTS results...
- S1P(1)-selective agonist, SEW2871, ameliorates ischemic acute renal failure
Y Hh Lien
Section of Nephrology, Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA
Kidney Int 69:1601-8. 2006
..This new class of renoprotective agent shows promise as a novel approach in preventing/treating ischemic acute renal failure...
- Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney
Alaa S Awad
Department of Medicine, Univ of Virginia, Charlottesville, VA, USA
Am J Physiol Renal Physiol 290:F1516-24. 2006
..The mechanism of protection is not known but may be related to peripheral lymphocyte depletion or direct effects on kidney cells expressing S1P1 receptor...
- Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity
Oncology Biology, GlaxoSmithKline, Collegeville, PA 19426, USA
Cancer Res 68:2366-74. 2008
..Immunohistochemical analysis of tumor xenografts after repeat dosing with GSK690693 showed reductions in phosphorylated Akt substrates in vivo. These results support further evaluation of GSK690693 as an anticancer agent...
- Utility of small-animal positron emission tomographic imaging of rats for preclinical development of drugs acting on the serotonin transporter
Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan
Int J Neuropsychopharmacol 12:1021-32. 2009
- The angiotensin receptor blocker, azilsartan medoxomil (TAK-491), suppresses vascular wall expression of plasminogen activator inhibitor type-I protein potentially facilitating the stabilization of atherosclerotic plaques
Christopher J French
Department of Medicine, Cardiovascular Research Institute, University of Vermont, Burlington, VT, USA
J Cardiovasc Pharmacol 58:143-8. 2011
..Accordingly, the suppression of PAI-1 expression by AZL-M may attenuate the evolution of atherosclerotic plaques vulnerable to rupture...
- Synthesis, fungicidal activity, and 3D-QSAR of pyridazinone-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles
Xia Juan Zou
State Key Laboratory for Structural Chemistry Studies of Stable and Unstable Species, Institute of Physical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, P R China, 100871
J Agric Food Chem 50:3757-60. 2002
A series of novel 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl] -2-arylamino-1,3,4-oxadiazoles, fungicidally active, were synthesized based on bioisosterism and tested in vivo against wheat leaf rust, Puccinia recondita...
- TAK-536, a new AT1 receptor blocker, improves glucose intolerance and adipocyte differentiation
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime, Japan
Am J Hypertens 20:579-86. 2007
..The effects of a new AT(1) receptor blocker (ARB), TAK-536, on insulin resistance were explored using type 2 diabetic KK-A(y) mice and compared with those of candesartan cilexetil (candesartan)...
- Pleconaril, a novel antipicornaviral agent
Naomi R Florea
Department of Pharmacy Research, Hartford Hospital, Hartford, Connecticut 06102, USA
Pharmacotherapy 23:339-48. 2003
..It shows promising results in treatment of picornaviral respiratory tract infections, meningitis, and other life-threatening infections...
- Emerging genetic therapies to treat Duchenne muscular dystrophy
Stanley F Nelson
Department of Physiological Science, UCLA, Los Angeles, CA 90095 7334, USA
Curr Opin Neurol 22:532-8. 2009
..The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called 'exon skipping' and 'nonsense codon suppression'...
- Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
Diabetes Obes Metab 13:1123-9. 2011
..We investigated the metabolic effects of the new angiotensin II type 1 receptor blocker azilsartan using the obese Koletsky rats superimposed on the background of the spontaneously hypertensive rats...
- Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models
Metabolic Disease Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd, Osaka, Japan
Eur J Pharmacol 669:84-93. 2011
..These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent...
- Defects in cGMP-PKG pathway contribute to impaired NO-dependent responses in hepatic stellate cells upon activation
Roman E Perri
Gastroenterology Research Unit, Department of Physiology, and Tumor Biology Program, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Am J Physiol Gastrointest Liver Physiol 290:G535-42. 2006
..Activating targets downstream from NO-cGMP in activated HSC may represent a novel therapeutic target for portal hypertension...
- Synthesis and biological evaluation of radioiodinated 2,5-diphenyl-1,3,4-oxadiazoles for detecting beta-amyloid plaques in the brain
Graduate School of Biomedical Sciences, Nagasaki University, 1 14 Bunkyo machi, Nagasaki 852 8521, Japan
Bioorg Med Chem 17:6402-6. 2009
..The novel radioiodinated 1,3,4-DPOD derivatives may be useful probes for detecting beta-amyloid plaques in the Alzheimer's brain...
- Peripheral analgesic blockade of hypernociception: activation of arginine/NO/cGMP/protein kinase G/ATP-sensitive K+ channel pathway
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, 14049 900, Sao Paulo, Brazil
Proc Natl Acad Sci U S A 101:3680-5. 2004
- Pharmaceuticals targeting nonsense mutations in genetic diseases: progress in development
Steven M Rowe
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA
BioDrugs 23:165-74. 2009
..These results, coupled with our improved understanding of how translation termination is regulated at PTCs, will help guide future directions of research involving this innovative treatment strategy for genetic diseases...
- Role of Rho-kinase in mediating contraction of chicken embryo femoral arteries
Department of Pediatrics, Maastricht University Medical Centre, School for Oncology and Developmental Biology GROW, P Debyelaan 25, P O Box 5800, 6202 AZ Maastricht, The Netherlands
J Comp Physiol B 180:427-35. 2010
..In summary, our findings are indicative of a role for Rho-kinase activity in depolarization- and agonist-induced force generation in chicken embryo femoral arteries...
- Synthesis, characterization and antimicrobial activity of some disubstituted 1,3,4-oxadiazoles carrying 2-(aryloxymethyl)phenyl moiety
Channamata Shankara Naveena
Department of Chemistry, Mangalore University, Mangalagangothri 575199, Karnataka, India
Eur J Med Chem 45:4708-19. 2010
..All the synthesized compounds were screened for their in vitro antibacterial and antifungal activity and some of them exhibited good activity...
- Nitric oxide-soluble guanylyl cyclase signaling regulates corticostriatal transmission and short-term synaptic plasticity of striatal projection neurons recorded in vivo
Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA
Neuropharmacology 58:624-31. 2010
..Moreover, phasic activation of NO signaling is likely to regulate short-term changes in corticostriatal synaptic plasticity via complex mechanisms involving both sGC-cGMP-dependent and independent pathways...
- Synthesis, characterization, and in vitro antimicrobial activities of 5-alkenyl/hydroxyalkenyl-2-phenylamine-1,3,4-oxadiazoles and thiadiazoles
Nida N Farshori
Department of Chemistry, Aligarh Muslim University, Aligarh, India
Bioorg Med Chem Lett 20:1933-8. 2010
..and thiosemicarbazides (4a-d), which on further refluxing with POCl(3) and Ac(2)O yielded corresponding 1,3,4-oxadiazoles (3a-d) and thiadiazoles (5a-d), respectively...
- Nitric oxide-mediated nonadrenergic noncholinergic relaxation of piglet pulmonary arteries decreases with postnatal age
Department of Pediatrics, University Hospital Maastricht, Research Institute Growth and Development GROW, Maastricht, The Netherlands
J Physiol Pharmacol 58:45-56. 2007
..In conclusion, NANC relaxation is present in neonatal pulmonary and mesenteric arteries and it is, at least partially, mediated through NO. NANC relaxation of porcine pulmonary and mesenteric arteries decreases with postnatal maturation...
- Keto-1,3,4-oxadiazoles as cathepsin K inhibitors
James T Palmer
Celera Genomics, Inc, 180 Kimball Way, South San Francisco, CA 94080, USA
Bioorg Med Chem Lett 16:2909-14. 2006
..This series thus represents a promising chemotype that could be used in diseases implicated by imbalances in cathepsin K activity such as osteoporosis...
- Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists
Department of Medicinal Chemistry, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran 14155 6153, Iran
Bioorg Med Chem Lett 15:3126-9. 2005
A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents...
- Aroylpropionic acid based 2,5-disubstituted-1,3,4-oxadiazoles: synthesis and their anti-inflammatory and analgesic activities
Faculty of Pharmacy, Jamia Hamdard University, Department of Pharmaceutical Chemistry, Hamdard Nagar, New Delhi 110062, India
Eur J Med Chem 44:2372-8. 2009
..The study showed that the cyclization of carboxylic group of aroylpropionic acids into an oxadiazole nucleus resulted in compounds having good anti-inflammatory and analgesic effects with reduced gastric irritation...
- Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
Bioorg Med Chem Lett 14:6057-9. 2004
A series of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles has been synthesized and screened for their anticonvulsant activities. Compound 3 shows considerable anticonvulsant activity both in PTZ and MES models...
- Design and synthesis of new 2-substituted-5-[2-(2-halobenzyloxy)phenyl]-1,3,4-oxadiazoles as anticonvulsant agents
Department of Medicinal Chemistry, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
Chem Pharm Bull (Tokyo) 56:509-12. 2008
A new series of 2-substituted-5-[2-(2-halobenzyloxy)phenyl]-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents...
- 2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)
Joseph S Warmus
Department of Chemistry, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA
Bioorg Med Chem Lett 18:6171-4. 2008
..This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor...
- Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: one more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity
Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495 009, CG, India
Bioorg Med Chem Lett 20:4168-72. 2010
..The results of the present studying validated that the pharmacophoric model with four binding sites is essential for anticonvulsant activity...
- Hypervalent iodine(III) mediated synthesis of novel unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles as antibacterial and antifungal agents
Department of Chemistry, Kurukshetra University, Kurukshetra 136 119, Haryana, India
Eur J Med Chem 45:4252-7. 2010
A series of novel 2,5-disubstituted 1,3,4-oxadiazoles 4 have been conveniently synthesized by oxidative cyclization of pyrazolylaldehyde N-acylhydrazones 3 promoted by iodobenzene diacetate under mild conditions (11 examples, up to 92% ..
- Synthesis of 3-aryl-5-decapentyl-1,2,4-oxadiazoles possessing antiinflammatory and antitumor properties
Natércia M Miranda Bezerra
Departamento de Quimica Fundamental, Centro de Ciencias Exatas e de Natureza, Universidade Federal de Pernambuco, CEP 50740 540 Recife, PE, Brazil
Farmaco 60:955-60. 2005
A simple, convenient and straightforward synthesis of 3-aryl-1,2,4-oxadiazoles 4a-f from arylamidoximes 1a-f and palmitic acid 2 is described. Compounds 4a-f are non-lethal in mice at four times the therapeutic dose (i.p...
- Vascular reactivity in intrapulmonary arteries of chicken embryos during transition to ex ovo life
Department of Pediatrics, University Hospital Maastricht, Research Institute Growth and Development, University of Maastricht, 6202 AZ Maastricht, The Netherlands
Am J Physiol Regul Integr Comp Physiol 282:R917-27. 2002
..Chicken embryo pulmonary arteries show a marked endothelium-dependent relaxation that is unaffected by transition to ex ovo life. Endothelium-derived NO seems to be the main mediator responsible for this relaxation...
- Optimization of subsite binding to the beta5 subunit of the human 20S proteasome using vinyl sulfones and 2-keto-1,3,4-oxadiazoles: syntheses and cellular properties of potent, selective proteasome inhibitors
Robert M Rydzewski
Department of Medicinal Chemistry, 180 Kimball Way, South San Francisco, California 94080, USA
J Med Chem 49:2953-68. 2006
..The resulting optimized P4-P3-P2 sequence was grafted onto a novel proteasome inhibitor warhead, 2-keto-1,3,4-oxadiazoles (KOD), to produce reversible, subnanomolar proteasome inhibitors that were 1000-fold selective versus cathepsin ..
- GSK690693 delays tumor onset and progression in genetically defined mouse models expressing activated Akt
Deborah A Altomare
Women s Cancer, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Clin Cancer Res 16:486-96. 2010
..The broad long-term objective of this project was to use preclinical cancer models with precisely defined genetic lesions to elucidate the efficacy of targeting Akt with GSK690693...
- The toxic and anti-feedant activity of 2H-pyridazin-3-one-substituted 1,3,4-oxadiazoles against the armyworm Pseudaletia separata (Walker) and other insects and mites
Institute of Pesticides and Pharmaceuticals, East China University of Science and Technology, Shanghai, 200237, China
Pest Manag Sci 59:933-9. 2003
The toxicities and anti-feedant activities of thirteen asymmetrical 1,3,4-oxadiazoles containing a 2H-pyridazin-3-one group were investigated...
- Differential efficacy of caspase inhibitors on apoptosis markers during sepsis in rats and implication for fractional inhibition requirements for therapeutics
Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories, Montreal, Quebec, Canada H9H 3L1
J Exp Med 199:199-207. 2004
..Furthermore, this requirement presents substantial therapeutic challenges owing to the need for persistent and complete caspase blockade...
- NO scavenging by 3-hydroxyanthranilic acid and 3-hydroxykynurenine: N-nitrosation leads via oxadiazoles to o-quinone diazides
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Goettingen, Berliner Strasse 28, D 37073 Goettingen, Lower Saxony, Germany
Nitric Oxide 19:237-44. 2008
..ion formation from diazonium ions of non-hydroxylated anilines, nitrogen is practically not released from oxadiazoles/quinone diazides at moderate temperatures...
- Synthesis of some new 2-(6-methoxy-2-naphthyl)- 5-aryl-1,3,4-oxadiazoles as possible non-steroidal anti-inflammatory and analgesic agents
Department of Post Graduate Studies and Research in Chemistry, Mangalore University, Mangalagangotri, India
Arch Pharm (Weinheim) 338:373-7. 2005
The synthesis of some new 2-(6-methoxy-2-naphthyl)-5-aryl-1,3,4-oxadiazoles (4a-k) has been described. Ethyl-6-methoxy-2-naphthoate (1) yielded on treatment with hydrazine hydrate to 6-methoxy-2-naphthoic acid hydrazide (2)...
- Synthesis and antimicrobial studies of a new series of 2-[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]-5-substituted-1,3,4-oxadiazoles
S L Gaonkar
Department of Studies in Chemistry, University of Mysore, Manasagangotri, India
Eur J Med Chem 41:841-6. 2006
A series of novel 2-[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]-5-substituted-1,3,4-oxadiazoles were synthesized by the oxidative cyclisation of hydrazones derived from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde and aroylhydrazines ..
- Synthesis and anticonvulsant activity of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles
Department of Medicinal Chemistry, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran 141556153, Iran
Bioorg Med Chem Lett 15:1863-5. 2005
A series of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles have been synthesized and evaluated as anticonvulsant agents. Compound 4b shows considerable anticonvulsant activity both in PTZ and MES models...
- Syntheses, antifeedant activity, and QSAR analysis of new oxa(thia)diazolyl 3(2H)-pyridazinones
Institute of Pesticides and Pharmaceuticals, East China University of Science and Technology, P O Box 544, 130 Meilong Road, Shanghai 200237, China
J Agric Food Chem 53:3120-5. 2005
..The results showed that dipole moment, molar refractivity, and log P are identified as critical parameters for chronic growth effects...
- Synthesis, antimicrobial, and anti-HIV-1 activity of certain 5-(1-adamantyl)-2-substituted thio-1,3,4-oxadiazoles and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-oxadiazoline-2-thiones
Ali A El-Emam
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Bioorg Med Chem 12:5107-13. 2004
..ethanolic potassium hydroxide yielded the corresponding 5-(1-adamantyl)-2-ethyl or substituted ethylthio-1,3,4-oxadiazoles 3a-c...
- Synthesis and antifeedant activity of new oxadiazolyl 3(2H)-pyridazinones
Institute of Pesticides and Pharmaceuticals, East China University of Science and Technology, P O Box 544, 130 Meilong Road, Shanghai 200237, P R China
J Agric Food Chem 51:152-5. 2003
..The compounds exhibited significant levels of activity. The feeding deterrency values of IIIa,j were 57% and 51% at 500 mg/kg concentration, respectively...
- Synthesis of Schiff bases of 2-amino-5-aryl-1,3,4-oxadiazoles and their evaluation for antimicrobial activities
Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Dr Hari Singh Gour University, Sagar, India
J Gen Appl Microbiol 51:133-41. 2005
Twenty Schiff bases of 2-amino-5-aryl-1,3,4-oxadiazoles have been synthesized with different aromatic aldehydes. The structures of the compounds were confirmed by nitrogen analysis, IR and 13C-NMR spectral data...
- Synthesis and biological evaluation of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides and 3,4-diphenyl-1,2,5-oxadiazoles as potential hybrid COX-2 inhibitor/nitric oxide donor agents
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8
Bioorg Med Chem 13:2749-57. 2005
..3,4-diphenyl-1,2,5-oxadiazole-2-oxides (3,4-diphenylfuroxans) and the corresponding N-desoxy 3,4-diphenyl-1,2,5-oxadiazoles (3,4-diphenylfurazans) analogs, were synthesized for in vitro evaluation as hybrid cyclooxygenase (COX) ..
- Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure-anti-mycobacterial activities
Institute of Chemistry, Academy of Sciences of Moldova, Chisinau, MD 2028, Republic of Moldova
Bioorg Med Chem 13:4842-50. 2005
The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer-aided study of their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) are reported...
- Nitric oxide preferentially induces type 1 T cell differentiation by selectively up-regulating IL-12 receptor beta 2 expression via cGMP
Department of Immunology and Bacteriology, University of Glasgow, Glasgow G11 6NT, United Kingdom
Proc Natl Acad Sci U S A 99:16186-91. 2002
..Our results also provide an example of the regulation of cytokine receptor expression by NO. The selectivity of such action via cGMP suggests that it is amenable to therapeutic intervention...
- Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate
Kerry L Homer
Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland 4072, Australia k homer
Br J Pharmacol 137:1071-81. 2002
..7. Thus inhibition of rat platelet aggregation by MAHMA NONOate (like GSNO) is largely ODQ-resistant and, by implication, independent of soluble guanylate cyclase. A likely mechanism of inhibition is activation of SERCA...
- Role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage in rats
J V R Medeiros
Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Ceara, Brazil
Br J Pharmacol 153:721-7. 2008
..Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage...