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Dissertations / Theses on the topic 'Thromboxanes – Antagonistes'

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1

Sbai, Brahim. "Les antagonistes des récepteurs du thromboxane A2." Bordeaux 2, 1995. http://www.theses.fr/1995BOR2P006.

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2

Perrin, Véronique. "Synthèse et caractérisation pharmacologique de nouveaux antagonistes potentiels des récepteurs du thromboxane A2." Lyon 1, 1996. http://www.theses.fr/1996LYO10314.

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Le thromboxane a#2 est un puissant constricteur des muscles lisses vasculaires et respiratoires ainsi qu'un agent de l'agregation plaquettaire. Il est implique dans des pathologies respiratoires, cardiovasculaires et renales. Compte tenu de l'etude des caracteristiques communes a de nombreux antagonistes connus, notre but etait de preparer des antagonistes des recepteurs du thromboxane a#2 possedant une structure 2-azanorbornane et ayant une fonction sulfone sur l'atome d'azote, ainsi que la chaine superieure, plus ou moins modifiee, des prostaglandines. Les differentes molecules obtenues ont ensuite ete soumises a des tests pharmacologiques in vivo sur les recepteurs vasculaires chez le rat conscient et in vitro sur les recepteurs plaquettaires chez le cobaye ; alors que les tests in vitro se sont averes en majorite negatifs, les tests in vivo ont permis de mettre en evidence une activite antagoniste sur les recepteurs vasculaires
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3

Traversa, Christel. "Synthèse et étude de nouveaux antagonistes potentiels du thromboxane A2 à partir d'aza-7-norbornadiènes." Lyon 1, 1994. http://www.theses.fr/1994LYO10305.

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Le thromboxane a#2 est un puissant agent constructeur des muscles lisses et un agregant plaquettaire implique dans l'hypertension arterielle, l'infarctus du myocarde, l'asthme et des maladies renales. Nous basant sur des caracteristiques communes a un grand nombre d'antagonistes connus, nous avons synthetise des molecules presentant comme structure de base un squelette 7-azanorbornane et la chaine superieure, complete ou non, des prostaglandines. Le squelette est obtenu par une reaction de diels-alder thermique entre le pyrrole 1-carboxylate de tertiobutyle et l'acetylene dicarboxylate de methyle. Le cycloadduit obtenu a pu etre transforme en aldehyde-ester sature selon deux voies. La premiere, apres l'hydrure de lithium et d'aluminium ; cependant, l'aldehyde est obtenu en melange d'isomeres. La seconde voie donne, par saponification, hydrogenation puis reduction selective de l'acide, un isomere pur. Cet aldehyde nous a alors permis, par reaction de wittig, d'introduire la chaine superieure de prostaglandines a six atomes de carbone. La chaine complete a pu etre obtenue par homologation de l'aldehyde puis condensation de wittig. Apres modification du substituant de l'azote, les molecules obtenues ont ete biologiquement testees soit in vitro sur des plaquettes de cobaye, soit in vivo sur des rats conscients. D'autres etudes ont ete menees en parallele pour eliminer la fonction ester restante sur le cycle de base et pour introduire une seconde fonction azotee dans la molecule. Ces dernieres voies n'ont pu encore aboutir
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4

Lacan, Fabrice. "Acides (2-(arylsulfonylimino)-2,3-dihydrothiazolyl)phenoxyacétiques antagonistes des récepteurs du thromboxana A2 : synthèse, étude structurale et pharmacologique." Bordeaux 2, 1997. http://www.theses.fr/1997BOR2B001.

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5

Riveron, Véronique. "Synthèse et étude de nouveaux antagonistes potentiels du thromboxane A2 et de la prostaglandine H2 faisant intervenir un squelette 2-azanorbornane." Lyon 1, 1993. http://www.theses.fr/1993LYO10293.

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Le thromboxane a2 est un puissant agent constricteur des muscles lisses et un agregant des plaquettes sanguines. Il intervient dans des pathologies cardiovasculaires et respiratoires. Au vu de la litterature, notre but etait d'obtenir des antagonistes des recepteurs du thromboxane a2 ayant un squelette 2-azanorbornane et incluant une fonction sulfonee sur l'azote, ainsi que la chaine alpha des prostaglandines (6 ou 7 atomes de carbone). La molecule finale comportant la chaine 5-hexenoique, a ete testee sur les recepteurs vasculaires chez le rat conscient normo-tendu, par observation des reponses du u 46619, agoniste connu des memes recepteurs: il s'est avere presenter une activite partielle et fugace a la dose de 50 mg/kg
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6

Fourcade, Olivier. "Rôle et mécanisme d'action de la sPLA2 de type ILA : hydrolyse après ectosytase et synthèse d'acide lysophatidique : inhibition de l'agrégation plaquettaire par le propofol : hydrolyse des phospholipides de nutritions parentérales." Toulouse 3, 2002. http://www.theses.fr/2002TOU30117.

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7

Harrold, Marc W. "Part 1, synthesis of trimetoquinol analogs as potential thromboxane A2 receptor antagonists ; Part 2, synthesis of permanently charged and permanently uncharged dopamine antagonists /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487584612165271.

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8

Convard, Thierry. "Mise au point et validation d'un protocole général de modélisation moléculaire : application aux antagonistes du récepteur du thromboxane A2." Bordeaux 2, 1998. http://www.theses.fr/1998BOR2B003.

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9

Markovich, Kimberly M. "Part 1. Synthesis of fluorinated catecholamine derivatives as potential adrenergic stimulants and thromboxane A? antagonists ; Part 2. Synthesis of hydrazinium analogs of dopamine agonists and antagonists /." The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487687485808709.

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10

Miljak, Marijan [Verfasser], and Christian [Akademischer Betreuer] Gratzke. "Effekte von Thromboxan-Rezeptor-Antagonisten auf die glattmuskuläre Kontraktion in der humanen Prostata / Marijan Miljak ; Betreuer: Christian Gratzke." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1126968226/34.

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11

Tantishaiyakul, Vimon. "Part I. Synthesis of idocatecholamine derivatives as adrenergic stimulants and thromboxane A₂ antagonists ; Part II. Synthesis of irreversible inhibitors of aldose reductase /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487677267730112.

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12

Jan, Ja-Ding, and 詹家鼎. "Design and Synthesis of Thromboxane Antagonists." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/06556561254749991477.

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Abstract:
碩士
朝陽大學
應用化學研究所
87
Thromboxane A2 is involved in many physiological functions. It is also the cause of many pathologicalconditions. For example: The increase in thromboxane A2 causes vascular contraction to produce atherosclerosis, thrombosis and asthma. The abnormal secretion of thromboxane A2 and platelet receptor activation may be one of the cause of thrombosis and atherosclerosis. Thromboxane antagonist may be a good approach to these diseases. According to past experience, potent thromboxane antagonist may contain the following pharmacophores, that is, a sulfonamide, an interphenylene ring and a carboxylic acid. The relative position of these three groups decided the potency of these antagonists. Synthesis of all these thromboxane antagonists, starting from Exo-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride 12, were achieved in a short and convenient manner, leading to enantiopure compounds in good overall yields.
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13

Xu, Ya-Fen, and 許雅芬. "Synthesis and Pharmacological Studies of Some Thromboxane Antagonists." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/04423668607120176846.

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14

Hsueh, Ying-Lung, and 薛穎隆. "Synthesis of Thromboxane Antagonists 3-Carboxyethylbenzyl-2-benzenesulfonamidobicyclo[2.2.1] heptane Derivatives." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/79735223406683524765.

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Abstract:
碩士
朝陽科技大學
應用化學系碩士班
90
Abstract Thromboxane A2 is involved in many physiological functions. It is also the cause of many pathological conditions. For example, the increase in thromboxane A2 causes vascular contraction to produce atherosclerosis, thrombosis and asthma. The abnormal secretion of thromboxane A2 and platelet receptor activation may be one of the causes of thrombosis and atherosclerosis. Thromboxane antagonist may be a good approach to these diseases. According to past experience, potent thromboxane antagonist may contain the following pharmacophores, that is, a sulfonamide, an interphenylene ring and a carboxylic acid. The relative position of these three groups decided the potency of these antagonists. Synthesis of all these thromboxane antagonists, starting from exo- 7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride 12, were achieved in 20 steps, leading to enantiopure compounds.
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15

郭浩蓁. "Synthesis and pharmacological characterization of bicyclo[2.2.1]heptyl-interphenylene thromboxane antagonists." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/63768293705894580040.

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Abstract:
碩士
國立成功大學
藥理學研究所
86
Thromboxane A2 is involved in thrombi formation. It is related to many cardiovascular diseases. Activation of the platelet thromboxane receptor leads to platelet aggregation and secretion of more thromboxane A2. Increase in thromboxane A2 causes vascular contraction. Abnormal platelet receptor activation may be related to thrombosis and atherosclerosis. On the contrary, activation of endothelial thromboxane receptor leads to an increase in production of prostacyclin that opposes thromboxane action. Therefore, selective inhibition of the platelet type receptor may be beneficial in the prevention of thrombosis and atherosclerosis. The objective of our study is to design and synthesize potent thromboxane antagonists with prolonged biological half-lives. According to our previous data, potent thromboxane antagonists may contain the following pharmacophores: a sulfonamide, an inter-phenylene ring and a carboxylic acid. These three groups may be concerned with the potency and activity of the antagonists on thromboxane receptors. Antagonist (±)IPA (2-[(3-phenyl- sulfonylaminobicyclo[2.2.1]hept-2-yl)methyl]-phenylpropanoic acid) was synthesized with biological activity. Preliminary studies also show IPA has potent inhibitory action on platelet aggregation.
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16

Hui-Fen-Yu and 余慧芬. "Screening of thromboxane antagonists and study on structure and activity relactionship." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/46049660286824412993.

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Abstract:
碩士
國立成功大學
藥理學研究所
87
Thromboxane A2 was a potent inducer of platelet aggregation and constrictor of vascular and respiratory smooth muscles. It had been implicated as a pathological mediator in many diseases. There were many TXA2 antagonists applied in clinical trials. So it was necessary to develop TXA2 antagonists. The purpose of this article was to screen compounds and to study the structure-activity relationship of TXA2 antagonists. This article included two purposes: (±)-IPA; (2-[(3-phenylsulfonylaminobicyclo[2.2.1]hept-2-yl)methyl]-phenylpropanoic acid synthesized previously in our laboratory had TXA2 antagonistic effects both on platelet and smooth muscle with high bioavailability. But (±)-IPA had low aqueous dissolution. In order to elevate aqueous dissolution, we got (±)-IPA analogues modifying from (±)-IPA. One purpose was to study the structure-activity relationship of (±)-IPA analogues. The other one was to screen compounds and expectantly to investigate new TXA2 antagonists. The first step of the experiments was using U-46,619 as TXA2 agonist to screen 39 compounds by human platelet aggregation test. After getting IC50 value of screened compounds, ADP, epinephrine and collagen were used as agonists to study detail mechanisms of effects. Finally, structure-activity relationship of IPA analogues was studied similarly. The summary of results were described into five parts: (1) A series of 1,2,4-oxadiazole compounds were found having TXA2 antagonistic effects. Among those compounds, Compound 2 was the most potent one having IC50 9.3±0.7mM. The structure contained 1,2,4-oxadiazole with the -COOH group of the a chain was the pharmacophores characterized by studying the structure-activity relationship. (2) Compound 41 on which 1°-COOH was replaced by an -CH2OH has TXA2 antagonistic activity. (3) The EP171 whose double bond of a chain was replaced by interphenylene group had TXA2 antagonistic effect. (4) Compound 40S was more potent than Compound 40R. (5) All of Compound 40S, Compound 40R, Compound 41S, Compound 41R, Compound 42a, and Compound 42b did not induce shape change of platelet. All IC50 >100mM. From our results, IPA analogues may have solved the short half life and metabolism problems of S-1,452. Base on structure and activity relationship studies, novel TXA2 receptor antagonist pharmacophores were discovered. It will provide new insights in the design of new TXA2 antagonist.
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