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Dissertations / Theses on the topic 'PDE5 inhibitors'

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Published: 4 June 2021

Last updated: 1 February 2022

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1

Wang, Guocheng. "Design, synthesis and development of PDE5 inhibitors." Thesis, Aston University, 2009. http://publications.aston.ac.uk/15405/.

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This research project is concerned with the design, synthesis and development of new phosphodiesterase 5 (PDE5) inhibitors with improved selectivities and lower toxicities. Two series of a 5 member and a 6 member ring fused heterocyclic compounds were designed, and synthesized. By alteration of starting materials and fragments, two virtual libraries, each is consisted of close to hundred compounds, were obtained successfully. The screening of sexual stimulation activity with rabbits demonstrated both groups of compounds were able to stimulate rabbit penile erection significantly. The following

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2

Reid, Anne Marie. "Raf-1 kinase inhibitor protein modulation of the cellular response to chemotherapeutic drugs and PDE5 inhibitors." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2497/.

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RKIP was initially discovered as an endogenous inhibitor of the ERK and NF-κB pathways,and was also shown to prolong the activation of GPCRs via inhibition of the GRK2 protein. Now increasing evidence has linked RKIP to a metastases suppressing and chemo-sensitising role in cancer cells.The chemo-sensitising effect of RKIP was investigated in a colon carcinoma cell line using a variety of chemotherapeutic agents from conventional agents to newer targeted therapies. Initial results suggested that role of RKIP in the modulation of chemotherapeutic drug response was at the level of apoptosis; the

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3

Kurian, Stefanie [Verfasser]. "Effects of combination therapy of PDE5 inhibitor sildenafil and multikinase inhibitors sorafenib and sunitinib in NSCLC / Stefanie Kurian." Gießen : Universitätsbibliothek, 2015. http://d-nb.info/1076760546/34.

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4

Santos, Filho Hilton Oliveira dos 1956. "Estudo clínico fase I de carbonato de lodenafila, um novo tipo de inibidor de fosfodiesterase 5 (PDE5), em voluntários saudáveis do sexo masculino = A phase I clinical trial of lodenafil carbonate, a new phosphodiesterase type 5 (PDE5) inhibitor, in healthy male volunteers." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309461.

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Orientador: Gilberto De Nucci<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-22T19:42:28Z (GMT). No. of bitstreams: 1 SantosFilho_HiltonOliveirados_D.pdf: 1622141 bytes, checksum: 5f817cf4a04ee643bdf7e261e5861691 (MD5) Previous issue date: 2013<br>Resumo: Carbonato de Lodenafila é um novo tipo de inibidor de fosfodiesterase 5 (PDE5) utilizado no tratamento da disfunção erétil. O presente estudo foi realizado para avaliar a segurança, tolerabilidade e farmacocinética do carbonato de lodenafila após a administração

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Tavallai, Mehrad. "INTRODUCING NOVEL COMBINATORIAL TARGETED THERAPIES IN MULTIPLE TYPES OF CANCER." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4088.

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The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be ove

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6

Schaffner, Denise [Verfasser], and Irmgard [Akademischer Betreuer] Merfort. "Investigations of hepatic hemodynamics and alterations in the NO-cGMP pathway in an animal model of liver fibrosis / cirrhosis suggest PDE5 inhibitors as promising adjunct in portal hypertension therapy." Freiburg : Universität, 2018. http://d-nb.info/1189583216/34.

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7

Megat, Salim. "Traitement de la douleur neuropathique : des antidépresseurs aux inhibiteurs de phosphodiestérases." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ085/document.

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Les antidépresseurs ont un effet antiallodynique qui dépend de la stimulation des récepteurs β2-adrénergiques. Ceux-ci stimulent la production d’adénosine monophosphate cyclique (AMPc) régulé par les phosphodiestérases de type 4 (PDE4). Nous avons ici étudié l’effet d’inhibiteurs de PDE (iPDE) sur la douleur neuropathique, grâce à des approches de pharmacologie comportementale chez la souris complétées par de l’imagerie calcium et des approches moléculaires. Nos résultats montrent un effet antiallodynique des iPDE4 et des iPDE5. L’action des iPDE4 est liée à une diminution d’expression du TNFα

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8

Clapham, John Christopher. "Characterisation and structural studies on dog heart cyclic nucleotide phosphodiesterase." Thesis, Birkbeck (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267913.

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9

Xu, Chenjia. "A Novel in vitro PDE7 Inhibitor Inhibits IL-2 Gene Expression in Activated T Cells and Induces Apoptosis in a B-cell Line and Monocytic Cell Line." Thesis, Boston College, 2013. http://hdl.handle.net/2345/3935.

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Thesis advisor: Thomas C. Chiles<br>Elevating intracellular cAMP levels can result in a wide range of anti-inflammatory effects and growth arrest and apoptosis in cancer cells, marking phosphodiesterases (PDEs) as potential targets for inflammatory diseases and cancer treatment. PDE7A is proposed to be a new therapeutic target for its ubiquitous expression in proinflammatory and immune cells. A Barbituric acid based compound, BC12 was identified as an in vitro PDE7 inhibitor in fission-yeast-based high-throughput screen. Analysis of this compound on the activation of Jurkat T lymphocytes, mous

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Joseph, Emlyn Clive. "Pathogenesis of arteriopathy induced by PDE III inhibitors in the rat and dog." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307684.

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11

Demirbas, Cakici Didem. "Identification and Characterization of PDE8 Inhibitors Using a Fission Yeast Based High-throughput Screening Platform." Thesis, Boston College, 2011. http://hdl.handle.net/2345/3051.

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Thesis advisor: Charles S. Hoffman<br>In this thesis, I describe the development of a screening platform for detecting PDE8A inhibitors using the cAMP-dependent glucose sensing pathway of the fission yeast Schizosaccharomyces pombe, which led us to discover several PDE8A selective inhibitors. In this system, the only PDE of the fission yeast is replaced with mammalian PDE8A1 in strains that have been engineered such that PDE inhibition is required to allow cell growth. Using this system, I screened 56 compounds obtained from PDE4 and PDE7 high throughput screens (HTSs) and identified a PDE4-PD

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12

Wan, Kah Fei. "Characterisation of phosphodiesterase inhibitory proteins (PDE#gamma#) signalling in human embryonic kidney 293 cells." Thesis, University of Strathclyde, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288596.

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13

Tippelt, Sabine [Verfasser]. "Untersuchung der Pathogenese der möglicherweise speziesspezifischen toxikologischen Effekte von PDE4-Inhibitoren bei Ratten / Sabine Tippelt." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2013. http://d-nb.info/1037885198/34.

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14

Kaur, Gurpreet. "Synthesis of Boronic Acid Based Sensors for Glucose and Sialic Acid and Synthesis of Novel and Selective PDE4 Enzyme Inhibitors." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_diss/9.

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The boronic acid functional group is known to bind compounds with the diol group tightly and reversibly in aqueous environment and has been used as a recognition moiety for the design of carbohydrate sensors. The first chapter of the dissertation studies the synthesis and substitution effect on the affinity and selectivity of a known boronic acid-based glucose sensor. In such a sensor design effort, the availability of a signaling event, whether it is fluorescence or UV, is crucial. The second chapter studies the detailed mechanism on how a well-known fluorescent boronic acid compound change

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15

Grommel, Sonja [Verfasser]. "Untersuchung möglicher positiver Effekte hinsichtlich der Aufrechterhaltung der Gravidität durch PDE4-Inhibitoren an Ratten / Sonja Grommel." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2013. http://d-nb.info/1037800826/34.

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16

SILVA, Jessy Rosanily Tavares Landim. "In vitro characterization of the antimalarial activity and mode of action of new PDEs and DHODH inhibitors against Plasmodium falciparum." Master's thesis, Instituto de Higiene e Medicina Tropical, 2019. http://hdl.handle.net/10362/75614.

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A malária é uma das doenças parasitárias mais antigas e continua a ser a que mais mortes provoca mundialmente atualmente. Pode ser causada por cinco espécies distintas de protozoários do género Plasmodium (P. falciparum, P. ovale, P. vivax, P.malariae e P. knowlesi), sendo o P. falciparum a espécie mais letal. O parasita é transmitido ao ser humano pela picada do mosquito fêmea do gênero Anopheles. aquando da refeição sanguínea. Em 2017, a Organização Mundial da Saúde relatou 219 milhões de casos de malaria em todo o mundo, sendo a grande maioria na região subsaariana do continente africano. A

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17

Barberot, Chantal. "Vers un nouvel outil d'étude de la reconnaissance hôte-ligand : conception de nouveaux inhibiteurs de PDE4 guidée par docking quantique, synthèse et évaluation biologique." Thesis, Reims, 2013. http://www.theses.fr/2013REIMS013/document.

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Dans la recherche de nouveaux traitements des maladies broncho-pulmonaires comme l'asthme et la broncho-pneumopathie chronique obstructive, les inhibiteurs de PDE4 sont des cibles intéressantes. Dans cette voie, notre laboratoire s'intéresse à la synthèse d'une nouvelle famille d'inhibiteurs à base pyridazinone. Pour cela, cette thèse couple la modélisation moléculaire (docking : développement méthodologique et application), la synthèse organique ainsi que des tests biologiques.Dans un premier temps, le développement du logiciel d'amarrage moléculaire AlgoGen a été poursuivi. AlgoGen (créé ini

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18

Adams, David. "Modulation of agonist-stimulated second messenger and contractile events in bovine tracheal smooth muscle with cyclic nucleotide PDE inhibitors." Thesis, University of Leicester, 1994. http://hdl.handle.net/2381/33624.

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The aim of this thesis was to investigate and characterize the effects of isoenzyme- selective phosphodiesterase (PDE) inhibitors on a range of biochemical and functional parameters in bovine airway smooth muscle in order to further our understanding of 'cross-talk' between different second messenger pathways in this tissue. Cyclic nucleotide levels were measured after selective or non-selective PDE isoenzyme inhibition under conditions of basal and stimulated adenylyl and guanylyl cyclase activity. These data led to the conclusion that PDE IV plays an important role in the regulation of agoni

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19

Kreißelmeier, Klaus-Peter [Verfasser]. "Therapeutische Effekte von Iloprost und dem PDE 3/4-Inhibitor Tolafentrin im Modell der Monocrotalin-induzierten chronischen pulmonalen Hypertonie der Ratte / Klaus-Peter Kreißelmeier." Gießen : Universitätsbibliothek, 2011. http://d-nb.info/1062973119/34.

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20

Nickum, Elisa A. "Analysis of Regulated Drugs Using Chromatographic and Spectrophotometric Techniques Coupled with Spectroscopy An Orthogonal Approach to Protecting Public Health." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1504799568245931.

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21

Kalsi, J. S. "The effect of soluble guanylate cyclase activators and a nitric oxide releasing PDE 5 inhibitor on cavernosal and anococcygeal smooth muscle function in conditions of nitric oxide deficiency." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1333229/.

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Introduction: PDE5 inhibitors improve erections by potentiating nitric oxide (NO)- cyclic guanosine monophosphate system. However, long-term diabetic patients have reduced efficacy secondary to dysfunction of NO system. The aim of this thesis was to investigate in-vitro effects of a PDE5 inhibitor (sildenafil), a soluble guanylate cyclase (sGC) activator (BAY41-2272) and an NO-releasing PDE5 inhibitor (NCX-911) on urogenital smooth muscle in conditions of NO deficiency. Method: The effect of these compounds was investigated on tone and electrical field stimulation-induced nitrergic relaxation

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22

Sormes, Michael [Verfasser], and Stefan [Akademischer Betreuer] Ückert. "Funktionelle Effekte selektiver Phosphodiesterase (PDE)-Inhibitoren auf die glatte Muskulatur der humanen Prostata / Michael Sormes. Klinik für Urologie und Urologische Onkologie im Zentrum Chirurgie der Medizinischen Hochschule Hannover. Betreuer: Stefan Ückert." Hannover : Bibliothek der Medizinischen Hochschule Hannover, 2010. http://d-nb.info/1010308475/34.

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23

Bollenbach, Maud. "Nouvelles cibles pour l'étude et le développement d'outils pharmacologiques originaux pour le traitement des douleurs neuropathiques." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF022.

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Les douleurs neuropathiques désignent une hypersensibilité du système nerveux central sensoriel. C’est une maladie chronique et handicapante qui touche environ 6% de la population française. Cependant, à l’heure actuelle, il n’existe pas de traitement spécifique et efficace. Dans le cadre de cette thèse, nous avons utilisé deux stratégies différentes afin de développer des outils pharmacologiques originaux pour traiter ces douleurs : une approche phénotypique autour de deux inhibiteurs de la surproduction de TNFα (un dérivé de 2-aminopyrimidine et un dérivé de pyridin-2-yl guanidine) et une ap

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24

Capdeville, Marion-Justine. "Études des cycles biogéochimiques des contaminants organiques dits « émergents » dans les systèmes aquatiques." Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14304/document.

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Les substances pharmaceutiques font partie du groupe des contaminants émergents du fait de leur intérêt récent dans les études environnementales comparativement à des polluants étudiés depuis plus longtemps tels que les pesticides. Elles correspondent aux principes actifs des médicaments et, à ce titre, sont responsables des propriétés pharmacologiques des médicaments. Ce sont donc des molécules biologiquement actives qui peuvent agir sur les organismes vivants présents dans les écosystèmes impactés. L’origine des substances pharmaceutiques dans l’environnement est variable mais les principale

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25

Chen, Bo-Guang, and 陳柏光. "Disposition of PDE5 Inhibitors in the Isolated Perfused Rat Liver." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/37594322795062623437.

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碩士<br>國立成功大學<br>臨床藥學研究所<br>96<br>Introduction： PDE5 inhibitors are used for the treatment of male erectile dysfunction and pulmonary arterial hypertension. The structures of PDE5 inhibitors are similar to cGMP and they are mainly metabolized by CYP3A and CYP2C9 isozymes in the liver. Currently, the interaction studies of PDE5 inhibitors are focused on the metabolic aspect and none of them has addressed on the transporter interactions. However, recent studies have demonstrated that sildenafil can inhibit the activity of MRP4, MRP5 and OATP. And it has beeen suggested that P-gp, in addition to C

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26

Chang, Tsu-Ya, and 張慈雅. "Anti-asthmatic effects of hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, potentiated by daidzein, a selective PDE3 inhibitor." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/88830513624619954883.

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碩士<br>臺北醫學大學<br>藥理學研究所<br>94<br>Selective PDE4 inhibitors increase cAMP level, therefore have bronchodilatory and anti-inflammatory effects, and is worth to develop for ameliorating asthma in the future. Selective PDE3 inhibitors also increase cAMP level. Whether addition or potentiation will be observed when they combine each other is the aim of the present study. Hesperetin (PDE4 inhibitor) at 100 μM dilated baseline tension of ovalbumin (OVA)-sensitized guinea pig trachealis. When combined with 100 μM of diadzein (PDE3 inhibitor), addition was observed. In addition, the relaxant effect of

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Chen, Shih-Yu, та 陳仕祐. "PDE4 and PDE3 Inhibitors Synergistically Inhibit Collagen-Induced Arthritis and IFN-γ and IL-17A Release in DBA/1 Mice". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/7x69w6.

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碩士<br>國立中央大學<br>生命科學系<br>104<br>Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease. It targets multiple joints with complex pathological processes. To date, the etiology of RA is not fully understood. Accumulating evidence indicates that cAMP-elevating agents can negatively modulate many inflammatory responses in virtually all immune inflammatory cells and thereby ameliorate inflammatory diseases. Type 4 phosphodieasterases (PDE4s) are the predominant cAMP-hydrolyzing enzymes in most immune cells, hence being important in controlling the intracellular cAMP concentration a

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28

Fernandes, Diogo Miguel Pereira. "Inibidores seletivos e não seletivos da fosfodiesterase no tratamento da DPOC." Master's thesis, 2018. http://hdl.handle.net/10316/82803.

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Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina<br>COPD is nowadays the world’s 4th cause of death with a prevision that in 2020 it becames the 3rd. In Portugal the estimated prevalence is 14,2%, leading to 8000 annual deaths. It is an important public health issue that requires a lot of health resources. COPD is characterized by a progressive and irreversible airflow limitation, with a combination of lung destruction and small airways obstruction. Inflammation is one of the major mechanisms that induce the disease and tobacco is the major and preventable c

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29

Lin, Yu-Yuan, and 林玉苑. "Regulation of LPS-induced inflammatory responses by PDE4 inhibitor in macrophages." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/09428785409479309990.

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碩士<br>國立中央大學<br>生命科學研究所<br>98<br>Type 4 cAMP-specific phosphodisterases (PDE4s), the enzymes that degrade the second messenger cAMP, play a critical role in regulation of intracellular cAMP concentration. It has been demonstrated that PDE4 isozymes are expressed at high levels in immune cells and PDE4 inhibitors exhibit anti-inflammatory effects. revious studies have shown that lipopolysaccharide (LPS) induced PDE4B expression and activity in macrophages, and this induction is associated with an increase in the production of TNF-?. This TNF-? responses was inhibited by the PDE4 inhibitor rolip

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30

Lin, Pei-Jung, and 林佩蓉. "Phosphodiesterase(PDE)Inhibitors Modulated Spontaneous Action Potential of Snail Central Neurons." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/00006037855537775825.

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碩士<br>國立臺灣大學<br>藥理學研究所<br>92<br>The roles of phosphodiesterase (PDE) on the spontaneous action potentials and the effects of phosphodiesterase (PDE) inhibitors on bursts of potential elicited by d-amphetamine were studied on RP4 neuron of snail, Achatina fulica Ferussac in vitro. PDE inhibitors used include: vinpocetine (PDE1 selective), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, PDE2 selective), milrinone (PDE3 selective), rolipram (PDE4 selective), sildenafil (viagra) (PDE5 selective) and the non-selective inhibitor, caffeine. Vinpocetine, EHNA, milrinone, rolipram and caffeine but not sil

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Tseng, Pin Jung, and 曾品榕. "Investigating the interactions of MY-5445, a PDE5 inhibitor, and LY3023414, a PI3K/mTOR dual inhibitor, with MDR-linked ATP-binding cassette proteins ABCB1 and ABCG2." Thesis, 2019. http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107CGU05114084%22.&searchmode=basic.

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Yu, Pei-Ju, and 游佩茹. "PDE Inhibitors and cAMP Signaling Regulate IFN-g and IL-17A Release from CD4+ T Cells in Mouse Models of Rheumatoid Arthritis." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/8rt83f.

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碩士<br>國立中央大學<br>生命科學系<br>102<br>Rheumatoid arthritis (RA) is a complicated, chronic autoimmune disorder that affects 1-2% population worldwide. It primarily attacks cartilage and bone of joints. The etiology of the disease still remains to be defined. Accumulating evidence indicates that elevation of intracellular cAMP concentration can suppress a vast spectrum of inflammatory responses in most immune cells and, thereby ameliorate chronic inflammatory diseases, such as asthma, COPD, and atopic dermatitis. Type 4 phosphodiesterases (PDE4s) are the major cAMP-hydrolyzing enzymes in various infla

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33

Bock, Katrin [Verfasser]. "Untersuchungen zu pharmakologischen Wirkungen des PDE4-Inhibitors Cilomilast und des β2-Agonisten [Beta-2-Agonisten] Isoxsuprin an bovinen Myometriumstreifen, isoliert perfundiertem Uterus und in vivo / vorgelegt von Katrin Bock". 2004. http://d-nb.info/97392022X/34.

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