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Ruthenium-Catalyzed CH Functionalization Of(Hetero)
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1465 Ruthenium-catalyzed C-H Functionalization of (Hetero)arenes KARTHIK DEVARAJ ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6214 ISBN 978-91-554-9783-5 UPPSALA urn:nbn:se:uu:diva-310998 2017 Dissertation presented at Uppsala University to be publicly examined in B22, BMC, Husargatan 3, Uppsala, Uppsala, Friday, 24 February 2017 at 09:30 for the degree of Doctor of Philosophy. The examination will be conducted in English. Faculty examiner: Professor Victor A. Snieckus (Department of Chemistry, Queen's University, Canada). Abstract Devaraj, K. 2017. Ruthenium-catalyzed C-H Functionalization of (Hetero)arenes. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1465. 59 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9783-5. This thesis concerned about the Ru-catalyzed C-H functionalizations on the synthesis of 2- arylindole unit, silylation of heteroarenes and preparation of aryne precursor. In the first project, we developed the Ru-catalyzed C2-H arylation of N-(2-pyrimidyl) indoles and pyrroles with nucleophilic arylboronic acids under oxidative conditions. Wide variety of arylboronic acids afforded the desired product in excellent yield regardless of the substituents or functional group electronic nature. Electron-rich heteroarenes are well suited for this method than electron-poor heteroarenes. Halides such as bromide and iodide also survived, further derivatisation of the halide is shown by Heck alkenylation. In order to find catalytic on-cycle intermediate extensive mechanistic experiments have been carried out by preparing presumed ruthenacyclic complexes and C-H/D exchange reactions. -
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wjpls, 2020, Vol. 6, Issue 8, 61-75 Review Article ISSN 2454-2229 Mitali et al. World Journal of Pharmaceutical and Life Science World Journal of Pharmaceutical and Life Sciences WJPLS www.wjpls.org SJIF Impact Factor: 6.129 INSULIN THERAPY AND IT’S NEW APPROACHES Tejaswini S. Kawanpure and Dr. Mitali M. Bodhankar* Gurunanak College of Pharmacy, Near Dixit Nagar, Nari Road, Nagpur- 440026. Corresponding Author: Dr. Mitali M. Bodhankar Gurunanak College of Pharmacy, Near Dixit Nagar, Nari Road, Nagpur- 440026. Article Received on 01/06/2020 Article Revised on 22/06/2020 Article Accepted on 12/07/2020 ABSTRACT Diabetes mellitus is a serious pathologic condition which is responsible for major healthcare problems worldwide Insulin replacement therapy has been used in the clinical Management of diabetes mellitus for more than 84 years. Insulin has remained indispensable in dispensable in management of diabetes mellitus since its discovery in 1921. Comparatively, a large percentage of world population is affected by diabetes mellitus, out of which approximately 5-10% with type 1 diabetes while the remaining 90% with type 2. The present mode of insulin administration is by the subcutaneous route through which insulin introduced into the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges that have adverse effect on oral route of insulin administration mainly includes rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and its lipophilicity. Approaches such as liposomes, micro emulsions, nano cubicle, insulin chewing gum and so forth have been prepared to ensure the oral delivery of insulin. -
Renato Wilberto Zilli Eficácia Em Longo Prazo Das
RENATO WILBERTO ZILLI EFICÁCIA EM LONGO PRAZO DAS GLIFLOZINAS VERSUS GLIPTINAS NO TRATAMENTO DO DIABETES MELLITUS TIPO 2 APÓS FALÊNCIA DA METFORMINA COMO MONOTERAPIA: REVISÃO SISTEMÁTICA E METANÁLISE EM REDE Tese apresentada ao Programa de Ciências Médicas da Faculdade de Medicina da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Processos Imunes e Infecciosos Orientador: Prof. Dr. Fabiano Pinheiro da Silva (Versão corrigida. Resolução CoPGr 6018/11, de 13 de outubro de 2011. A versão original está disponível na Biblioteca da FMUSP) São Paulo 2017 Dados Internacionais de Catalogação na Publicação (CIP) Preparada pela Biblioteca da Faculdade de Medicina da Universidade de São Paulo ©reprodução autorizada pelo autor Zilli, Renato Wilberto Eficácia em longo prazo das gliflozinas versus gliptinas no tratamento do diabetes mellitus tipo 2 após falência da metformina como monoterapia : revisão sistemática e metanálise em rede / Renato Wilberto Zilli ‐‐ São Paulo, 2017. Tese(doutorado)--Faculdade de Medicina da Universidade de São Paulo. Programa de Ciências Médicas. Área de concentração: Processos Imunes e Infecciosos. Orientador: Fabiano Pinheiro da Silva. Descritores: 1.Diabetes mellitus tipo 2 2.Metanálise 3.Terapia combinada 4.Falha de tratamento 5.Metformina 6.Inibidores da dipeptidil peptidase IV 7.Transportador 2 de glucose‐sódio/inibidores 8.Empagliflozina 9.Dapagliflozina 10.Saxagliptina USP/FM/DBD ‐302/17 Esta tese de doutorado está de acordo com as seguintes normas, em vigor no momento desta publicação: Referências: adaptado de International Committee of Medical Journals Editors (Vancouver). Guia de apresentação e dissertações, teses e monografias. Elaborado por Anneliese Cordeiro da Cunha, Maria Julia de A.L. -
(12) Patent Application Publication (10) Pub. No.: US 2016/0220631 A1 Mezey Et Al
US 2016O220631A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0220631 A1 Mezey et al. (43) Pub. Date: Aug. 4, 2016 (54) METHODS OF MODULATING Publication Classification ERYTHROPOESS WITH ARGINNE VASOPRESSIN RECEPTOR 1B MOLECULES (51) Int. Cl. A638/II (2006.01) (71) Applicant: THE USA, AS REPRESENTED BY A613 L/404 (2006.01) THE SECRETARY DEPARTMENT A613 L/46.5 (2006.01) OF HEALTH AND HUMAN A638/8 (2006.01) SERVICES, Bethesda, MD (US) A6II 45/06 (2006.01) (52) U.S. Cl. (72) Inventors: Eva M. Mezey, Rockville, MD (US); CPC ............. A61K 38/11 (2013.01); A61 K38/1816 Balazs Mayer, Budakeszi (HU); (2013.01); A61K 45/06 (2013.01); A61 K Krisztian Nemeth, Budapest (HU); 3 1/465 (2013.01); A61 K31/404 (2013.01) Miklos Krepuska, Rockville, MD (US) (73) Assignee: The USA, as represented by the (57) ABSTRACT Secretary, Departm-ent of Health and Disclosed are methods of modulating erythropoiesis with Human Service, Bethesda, MD (US) arginine vasopressin receptor 1B (AVPR1B) molecules, such Appl. No.: as AVPR1B agonists or antagonists. In one example, a (21) 15/022,531 method of stimulating erythropoiesis is disclosed including (22) PCT Fled: Oct. 1, 2014 administering an effective amount of an AVPR1B stimulatory molecule to a subject in need thereof, thereby stimulating (86) PCT NO.: PCT/US2O14/058613 erythropoiesis. Also disclosed is a method of stimulating hematopoetic stem cell (HSC) proliferation which includes S371 (c)(1), administering an effective amount of an AVPR1B stimulatory (2) Date: Mar. 16, 2016 molecule to a subject in need thereof, thereby stimulating HSC proliferation. -
Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: a Systematic Review and Meta-Analysis
Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis by Sanaz Kamalinia A thesis submitted in conformity with the requirements for the degree of Master of Science Institute of Medical Sciences University of Toronto © Copyright by Sanaz Kamalinia (2019) Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: A Systematic Review and Meta- Analysis Sanaz Kamalinia Master of Science Institute of Medical Sciences University of Toronto 2019 Abstract Background : Evaluation of hypoglycemia risk relative to placebo with new antihyperglycemic agents (AHA) including the dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose co-transporter- 2 inhibitors (SGLT2i) remains inconclusive. Objective: This systematic review and meta-analysis aimed to assess risk of any and severe hypoglycemia with new AHA relative to placebo by excluding studies with background sulfonylureas and insulin. Methods: Randomized, placebo-controlled studies, 12 weeks or greater in duration were considered for inclusion. Studies allowing background use of any other AHA, apart from metformin, were excluded. This study is registered with PROSPERO (CRD42018095458). Results: 141 studies included in the meta-analysis demonstrate that relative to placebo, risk of any and severe hypoglycemia did not significantly differ for any new AHA. ii Acknowledgments First and foremost, I wish to express my sincere gratitude to my program advisor committee members. To my supervisor Dr Tobe, thank you for accepting me as your student and presenting me with this challenge. I thoroughly enjoyed it. Especially given your positive words of encouragement and insightful guidance for every step of this journey. -
Constitutive Endocytic Cycle of the CB1 Cannabinoid Receptor. Christophe Leterrier, Damien Bonnard, Damien Carrel, Jean Rossier, Zsolt Lenkei
Constitutive endocytic cycle of the CB1 cannabinoid receptor. Christophe Leterrier, Damien Bonnard, Damien Carrel, Jean Rossier, Zsolt Lenkei To cite this version: Christophe Leterrier, Damien Bonnard, Damien Carrel, Jean Rossier, Zsolt Lenkei. Constitutive endocytic cycle of the CB1 cannabinoid receptor.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (34), pp.36013-36021. 10.1074/jbc.M403990200. hal-00250336 HAL Id: hal-00250336 https://hal.archives-ouvertes.fr/hal-00250336 Submitted on 6 Feb 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Supplemental Material can be found at: http://www.jbc.org/cgi/content/full/M403990200/DC1 THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No. 34, Issue of August 20, pp. 36013–36021, 2004 © 2004 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A. Constitutive Endocytic Cycle of the CB1 Cannabinoid Receptor*□S Received for publication, April 9, 2004, and in revised form, June 9, 2004 Published, JBC Papers in Press, June -
Dipeptidyl Peptidase IV (DPP4) Inhibitors As Potential
Supporting Materials Drug repurposing: Dipeptidyl peptidase IV (DPP4) inhibitors as potential agents to treat SARS-CoV-2 (2019-nCov) infection Praveen P. N. Rao 1*, Amy Trinh Pham 1, Arash Shakeri 1, Amna El Shatshat 1, Yusheng Zhao 1, Rahul C. Karuturi 1 and Ahmed A. Hefny 1 School of Pharmacy, University of Waterloo, Health Sciences Campus, 200 University Ave West, Waterloo, Ontario N2L 3G1, Canada *Corresponding author Praveen P. N. Rao, School of Pharmacy, Health Sciences Campus, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1, phone: 519-888-4567; ext: 21317; email: [email protected] Contents 1. Figure S1: Binding modes of DPP4 inhibitors anagliptin (A), alogliptin (B), trelagliptin (C) and sitagliptin (D) in the SARS-CoV-2 Mpro protomer 2. Figure S2: Binding modes of DPP4 inhibitors teneligliptin (A) and gosogliptin (B) in the SARS-CoV-2 Mpro protomer 3. Figure S3: Electrostatic surface potential map of SARS-CoV-2 Mpro protomer (A) and (B) dimer 4. Figure S4: Binding modes of DPP4 inhibitors gemigliptin, linagliptin and evogliptin in the MERS-CoV 3CLpro dimer 5. Figure S5: Pharmacophore model to design SARS-CoV-2 Mpro dimer inhibitors based on the docked poses of DPP4 inhibitors - gemigliptin, linagliptin and evogliptin 6. Figure S6: 2D Interaction map of linagliptin in the active sites of the serine protease DPP4 and cysteine protease SARS-CoV-2 Mpro 7. Table S1: Physicochemical properties of DPP4 inhibitors and the SARS-CoV-2 Mpro dimer inhibitor 1 1 Figure S1. Binding modes of DPP4 inhibitors anagliptin (A), alogliptin (B), trelagliptin (C) and sitagliptin (D) in the SARS-CoV-2 Mpro protomer (PDB ID: 6Y2F). -
Engagement of Β-Arrestin by Transactivated Insulin-Like Growth Factor Receptor Is Needed for V2 Vasopressin Receptor-Stimulated ERK1/2 Activation
Engagement of β-arrestin by transactivated insulin-like growth factor receptor is needed for V2 vasopressin receptor-stimulated ERK1/2 activation Geneviève Oligny-Longpréa, Maithé Corbanib, Joris Zhoua, Mireille Hoguea, Gilles Guillonb, and Michel Bouviera,1 aInstitut de Recherche en Immunologie et Cancérologie, Département de Biochimie and Groupe de Recherche Universitaire sur le Médicament, Universitéde Montréal, Montréal, QC, Canada H3C 3J7; and bInstitut de Génomique Fonctionnelle, Département d’Endocrinologie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5203, Institut National de la Santé et de la Recherche Médicale Unité 661, Universités Montpellier I et II, 34094 Montpellier Cedex 05, France Edited* by Jean-Pierre Changeux, Institut Pasteur, Paris, France, and approved March 9, 2012 (received for review August 12, 2011) G protein-coupled receptors (GPCRs) have been shown to activate ceptor (EGFR) and has only been described for EGFR ligands the mitogen-activated protein kinases, ERK1/2, through both G thus far (5, 6). Although GPCR-mediated transactivation of protein-dependent and -independent mechanisms. Here, we de- several other RTKs [including the PDGF (7), FGF (8), VEGF scribe a G protein-independent mechanism that unravels an un- (9), and tropomyosin-receptor kinase A (TrkA) (10) receptors] anticipated role for β-arrestins. Stimulation of the V2 vasopressin leading to MAPK activation has been documented, the specific receptor (V2R) in cultured cells or in vivo in rat kidney medullar mechanism responsible for the RTK engagement remains poorly collecting ducts led to the activation of ERK1/2 through the metal- characterized. Intracellular scaffolding that promotes the forma- loproteinase-mediated shedding of a factor activating the insulin- tion of protein complexes with nonreceptor tyrosine kinases, such – like growth factor receptor (IGFR). -
Dipeptidyl Peptidase-4 Inhibitors and the Risk of Heart Failure: a Systematic Review and Meta-Analysis
CMAJ OPEN Research Dipeptidyl peptidase-4 inhibitors and the risk of heart failure: a systematic review and meta-analysis Subodh Verma MD PhD, Ronald M. Goldenberg MD, Deepak L. Bhatt MD MPH, Michael E. Farkouh MD MSc, Adrian Quan MPhil, Hwee Teoh PhD, Kim A. Connelly MBBS PhD, Lawrence A. Leiter MD, Jan O. Friedrich MD DPhil Abstract Background: Given recent discrepant results from randomized controlled trials (RCTs), we examined the totality of RCT evidence assessing the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and heart failure. Methods: MEDLINE, Embase and ClinicalTrials.gov were searched without language restrictions to August 2016 for RCTs compar- ing DPP-4 inhibitors to placebo or no therapy for a period of 24 weeks or more. We included all heart failure outcomes when listed either as a serious adverse event or adverse event. Pooled analyses used random-effects. Results: We identified 100 RCTs (n = 79 867) — 3 large cardiovascular-safety RCTs (SAVOR-TIMI 53[saxagliptin]/n = 16 492, EXAMINE[alogliptin]/n = 5380, and TECOS[sitagliptin]/n = 14 735), and 97 smaller RCTs with a primary outcome that was usually change in glycated hemoglobin. Virtually all RCTs were high-quality, multicentre, placebo-controlled trials. A total of 96% (1192/1244) of heart failure events were prespecified, blindly adjudicated and required hospital admission. Pooled results suggested a 13% increase in heart failure (relative risk [RR] 1.13, 95% confidence interval [CI] 1.01–1.26, I2 = 0%; 32 RCTs, n = 54 640, 1244 events). When including only the 3 large RCTs, the increase was similar, but not significant (RR 1.14, 95% CI 0.97–1.32; 3 RCTs, n = 36 543, 1169 adjudicated events; number needed to harm 246) owing to heterogeneity (I2 = 42%), which lead to wider CIs, because SAVOR- TIMI 53 showed increased heart failure (RR 1.26, 95% CI 1.06–1.49) and TECOS showed no effect (RR 1.00, 95% CI 0.83–1.19). -
An Empirical Account of Defamation Litigation in China
Columbia Law School Scholarship Archive Faculty Scholarship Faculty Publications 2006 Innovation through Intimidation: An Empirical Account of Defamation Litigation in China Benjamin L. Liebman Columbia Law School, [email protected] Follow this and additional works at: https://scholarship.law.columbia.edu/faculty_scholarship Part of the Torts Commons Recommended Citation Benjamin L. Liebman, Innovation through Intimidation: An Empirical Account of Defamation Litigation in China, 47 HARV. INT'L L. J. 33 (2006). Available at: https://scholarship.law.columbia.edu/faculty_scholarship/554 This Article is brought to you for free and open access by the Faculty Publications at Scholarship Archive. It has been accepted for inclusion in Faculty Scholarship by an authorized administrator of Scholarship Archive. For more information, please contact [email protected]. VOLUME 47, NUMBER 1, WINTER 2006 Innovation Through Intimidation: An Empirical Account of Defamation Litigation in China Benjamin L. Liebman* INTRODUCTION Consider two recent defamation cases in Chinese courts. In 2004, Zhang Xide, a former county-level Communist Party boss, sued the authors of a best selling book, An Investigation into China's Peasants. The book exposed official malfeasance on Zhang's watch and the resultant peasant hardships. Zhang demanded an apology from the book's authors and publisher, excision of the offending chapter, 200,000 yuan (approximately U.S.$25,000)' for emotional damages, and a share of profits from sales of the book. Zhang sued 2 in a local court on which, not coincidentally, his son sat as a judge. * Associate Professor of Law and Director, Center for Chinese Legal Studies, Columbia Law School. -
Challenge of Diabetes Mellitus and Researchers' Contributions to Its
Open Chemistry 2021; 19: 614–634 Review Article Ayodele T. Odularu*, Peter A. Ajibade Challenge of diabetes mellitus and researchers’ contributions to its control https://doi.org/10.1515/chem-2020-0153 from the beta cells in the pancreas [1]. The outcome is received November 28, 2018; accepted June 30, 2020 either high blood level/high glucose level (that is hyper- )[– ] Abstract: The aim of this review study was to assess the glycemia 1 6 or low blood level/high glucose level ( )[ ] past significant events on diabetes mellitus, transforma- that is hypoglycemia 7,8 . Complications arising from tions that took place over the years in the medical records high and low glucose levels when not treated lead to - of treatment, countries involved, and the researchers who atherosclerosis, ocular disorder, diabetic retinopathy, car - brought about the revolutions. This study used the con- diac abnormalities, cardiovascular diseases, renal dys [ – ] tent analysis to report the existence of diabetes mellitus function, and other diseases of the blood vessels 9 11 . ff and the treatments provided by researchers to control it. Medications are failing with side e ects, and there is The focus was mainly on three main types of diabetes the likelihood of more widespread diabetes this coming (type 1, type 2, and type 3 diabetes). Ethical consideration decade because of urbanization, growing and aging - has also helped to boost diabetic studies globally. The states of people, and increasing childhood and adult obe [ – ] research has a history path from pharmaceuticals of sities 12 15 . The present statistics of diabetic patients organic-based drugs to metal-based drugs with their is alarming with the prediction of higher subjects. -
Xbhi -- New Jordans 2017 Release
xbhi - new jordans 2017 Release Nike Kobe 8 "Lakers" PE tushang 2013-12-08 23:02:15 This season, Bryant led the Lakers record is not very satisfactory, but Kobe Bryant in his sneakers aspect is progress soon, the network exposed a pair of Nike Kobe 8 "Lakers" PE, black shoe color, with purple outsole, I think Kobe Bryant will be in the playoffs this pair of shoes to wear it? ; ; ; [Chinese shoes Network - Brand Dynamics] 2011 domestic market share beyond adidas Anta desire. ; ; ; Anta margin has increased to 42.8%, net profit for more than Li Ning, the number of stores planned by the end of this year to break ten thousand. ; ; ; during the Chengdu body Expo May 13, Zheng Jie ANTA president said in an interview, in terms of cost control, Anta has a complete set of cost management system, such as bidding bidding mechanism, and moving production to lower-cost regions. ; ; ; on the same day, Vice President of ANTA Group Lai Shixian to Anhui Province Fengzhen study, understand Anfeng industrial park, as well as anfeng vocational secondary schools. These are likely to provide protection for the lower cost of production. ; ; ; ANTA Sports, said Zhang Tao, vice president, Anta has factories in Anhui, because of their own factories, companies need to do "feel" will be very rich, know this place now has been how, how much labor wages actually rose, the material's up a few points. In addition to Anhui, regional Anta considered include Henan and other places. ; ; ; Zheng Jie said, the share of the foundry than Anta to a large number of its own factories, but also to help guide providers to lower average labor cost areas metastasis.