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1
Mariappan, G. "Cardioprotective properties of pyrazotone derivatives in myocardial ischemic reperfusion injury." Thesis, University of North Bengal, 2011. http://hdl.handle.net/123456789/1501.
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Vetica, Fabrizio [Verfasser]. "Organocatalytic Asymmetric Synthesis of Isochromanones, Tetranortriterpenoids and Pyrazolone Derivatives / Fabrizio Vetica." München : Verlag Dr. Hut, 2018. http://d-nb.info/1155056213/34.
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Motson, Graham Robert. "Coordination chemistry of 3-(2'-pyridyl) pyrazole derivative ligands." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391153.
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Nakhai, Azadeh. "Synthetic studies of nitrogen containing heterocycles, particularly pyrazole and benzotriazine derivatives." Stockholm, 2009. http://diss.kib.ki.se/2009/978-91-7409-687-3/.
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Yazici, Ceyda. "Synthesis Of 4-iodopyrazole Derivatives." Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/3/12609750/index.pdf.
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Pyrazoles have been studied for over a century as an important class of
heterocyclic compounds and continue to attract considerable interest due to the
broad range of biological activities they possess. The electrophilic cyclization of
the acetylenic hydrazones initiated by molecular iodine could provide new ways of
synthesizing biologically active 4-iodopyrazole derivatives, which are important
precursors for the synthesis of highly substituted pyrazole derivatives. For this
reason, we investigated the synthesis of 4-iodopyrazole derivatives, such as 1-aryl-
5-alkyl/aryl-4-iodopyrazoles, starting from phenylhydrazine and ,-acetylenic
aldehyde derivatives. Initially, ,-acetylenic aldehydes were synthesized by
formylation reaction of corresponding alkynes with DMF. Then, hydrazone
derivatives of these aldehydes were prepared by heating them with
phenylhydrazine in a neat manner at 55 °C for 5 h. Finally, acetylenic phenyl hydrazone derivatives were subjected to electrophilic cyclization by treating with excess molecular iodine at 80 °
C for 3 h. Although electrophilic cyclization is commonly used in organic chemistry, it has not been employed for the cyclization of acetylenic phenyl hydrazones to pyrazole derivatives. Under optimized conditions, these reactions afforded 1-aryl-5-alkyl/aryl-4-iodopyrazole derivatives in moderate to good yields as the single or the major product of the reactions. In some cases, 1-aryl-5-alkyl/arylpyrazole derivatives resulted from these reactions as minor products. In conclusion, 4-iodopyrazole derivatives were synthesized for the first time directly from acyclic starting materials, ,-acetylenic phenylhydrazones and iodine, via electrophilic cyclization.
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Rango, Enrico. "PRECLINICAL CHARACTERIZATION OF SFK INHIBITORS, PYRAZOLO[3,4-d]PYRIMIDINE SCAFFOLD-BASED DERIVATIVES, FOR CANCER TREATMENT." Doctoral thesis, Università di Siena, 2021. http://hdl.handle.net/11365/1140389.
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The first part of this thesis essentially focuses on the preclinical characterization of Si306, a pyrazolo[3,4-d]pyrimidine derivative, identified as a very promising anticancer agent. This compound has shown a favorable in vitro and in vivo activity profile against neuroblastoma (NB) and glioblastoma (GBM) models by acting as a competitive inhibitor of c-Src tyrosine kinase. Nevertheless, the good antitumor activity of Si306 is associated with sub-optimal aqueous solubility, which might hinder its further development. In this context, drug delivery systems were developed to overcome the poor aqueous solubility obtaining suitable formulations for their in vivo use in the treatment of NB. Si306 was encapsulated in liposomal nanoparticles: i. Stealth liposomes and ii. Immunoliposomes decorated with AntiGD2 monoclonal antibody, which specifically binds GD2 antigen expressed by NB cells. Both liposomal suspensions resulted stable and showed excellent morphological and physio-chemical properties. The liposomal suspensions exhibited increased cytotoxic activity against different NB cell lines; in particular, AntiGD2-decorated liposomes, due to the interaction with the antigen, showed the ability to bind and be internalized in different NB cells and the cellular association increases proportionally with increasing GD2 antigen expression. The pharmacokinetic (PK) and tissue biodistribution (BD) profiles were evaluated by treating healthy male mice intravenously at two dosages of 5 and 25 mg of Si306/kg of body weight. Higher plasma exposure of Si306 was observed when it is delivered by liposomes compared to Si306 administered in free form. Moreover, an immediate distribution of Si306 followed by a concentration decrease in a time-dependent manner was observed in all organs analyzed. An increased concentration of Si306 was observed in the liver, spleen, and lungs when it is delivered by liposomes. A preliminary PK and BD study on NB orthotopic mouse model demonstrated increased tumor uptake of Si306 when it is encapsulated in liposomes compared to drug-free. Finally, in vivo efficacy and survival studies conducted on orthotopic NB mice models revealed the ability of Si306-loaded immunoliposomes to reduce tumor growth and to significantly increase the survival rate.
In the second section, gold nanoparticles (AuNPs) conjugated to Si306 were developed to improve its solubility, but also to increase its ability to cross the blood-brain barrier and to have a therapeutic action against (GBM). This section describes the design, the preparation, and the characterization of AuNPs conjugated with Si306. AuNPs-Si306 showed a good loading efficacy (65%), optimal stability in polar media and human plasma, and a suitable morphological profile. Antitumoral activity of AuNPs-Si306 was evaluated in in vitro GBM model, also in combination with radiotherapy (RT). Results demonstrated that AuNPs had a basal radio-sensitization ability and that AuNPs-Si306, when used in combination with RT, was more effective in inhibiting tumor cell growth with respect AuNPs and free Si306.
In the third section, Si409, a pyrazolo[3,4-d]pyrimidine derivative, showed the ability to inhibit key members of SFK involved in Diffuse Large B-cell Lymphoma (DLBCL) and to reduce the proliferation of several B-cell tumor cell lines. Also, low cytotoxic activity of Si409 was measured on healthy human peripheral blood mononuclear cells (PBMCs). Si409 showed to be safe by exhibiting a reduction in hERG current but only at concentrations at least 10-fold higher than the median IC50 value recorded in tumor cell lines. PK studies showed high phase II metabolism caused by glucuronide conjugation, which reduces plasma levels and increases the clearance of Si409. Despite the low plasma levels, the treatment with Si409 in ABC-DLBCL xenograft mouse model revealed a considerable volumetric reduction of the tumor mass suggesting an interesting in vivo pharmacological potency of this compound.
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GRECO, CHIARA. "Synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine derivatives active as SGK1, Fyn and Src kinases inhibitors." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/1001600.
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The pathogenesis of many cancers is characterized by mutations, overexpression and dysregulation of protein kinases. As a result, increasing attention has been directed towards the identification of novel kinase inhibitors for cancer therapy.
The work performed here focuses on the synthesis of a series of pyrazolo[3,4-d]pyrimidine derivatives as inhibitors of the serine-threonine kinase SGK1, and the tyrosine kinases Fyn and Src.
The first set of compounds are analogues of the in house SGK1 inhibitor SI113 which had previously demonstrated anti-cancer activity. In fact SI113 resulted to be active on various cancer cell lines and in an in vivo hepatocellular carcinoma model. The new set of SI113 analogues are characterized by different anilines, ammines and a morpholine group in C4 and are decorated in C6 with polar chains, i.e. ethanolamine, diethanolamine, ethylene glycol and ethylenediamine. The double bond on the N1 side chain which is essential for the activity of compounds toward SGK1, was maintained.
The structures of the second set of compounds, instead, are related to the in house Fyn inhibitor SI308. From previously studies on the first generation of Fyn inhibitors, SI308 was reported as the most potent compound, demonstrating both antiproliferative activity on cancer cell lines and the ability to inhibit protein Tau phosphorylation in a cellular model of Alzheimer’s disease. The new generation of SI308 related compounds present a methyl group at the C6 position and on C3 the phenyl ring is either unsubstituted or presents a methyl group in para position.
Preliminary screening using enzyme activity assays demonstrates that some of the novel compounds are active and therefore suitable for further study using in vitro models. It is predicted that subsequent in vitro data will aid in the design of future compounds.
Furthermore, previous data on another in house compound SI306, which is active on tyrosine kinase Src, reported promising results on an in vivo xenograft model of neuroblastoma. To further study this biological activity, SI306 was re- synthesized and additional experiments were performed on in vitro models. Testing of this compound on MYCN-amplified neuroblastoma cell lines HTLA-230 and SK-N-BE-2C further confirmed the activity of SI306 and provide increased support for the inhibition of Src as a valid approach for neuroblastoma treatment.
Finally, further in vitro studies were performed on of the three previously cited in house pyrazolo[3,4-d]pyrimidines, SI306, SI308 and SI113, using patient derived glioblastoma multiforme (GBM) cell lines. This final set of work was undertaken during a visiting research fellowship period and performed in collaboration with the School of Pharmacy at the University of Nottingham (United Kingdom). Kinase inhibitor activity has been evaluated on series of patient derived GBM cell lines isolated from both the central tumor core (GCE28) and from the invasive margin of the tumor (GIN28 and GIN8). The use of such phenotypically relevant in vitro models represents an important step for GBM drug development and screening. The results gathered using these relevant cell models further demonstrate the anti-cancer activity of the pyrazolo[3,4-d]pyrimidines compounds. Moreover, investigating the compounds in combination with one another reveals that synergy can be achieved and this finding has additional implications for potentially overcoming GBM drug resistance. Additionally, to overcome the low water solubility of our pyrazolo[3,4-d]pyrimidines compounds, formulations of the lead compounds (SI306, SI308 and SI113) were prepared using miniaturized screening process based on inkjet printing technology6. The observed activity of our compounds in vitro taken together with their successful formulation highlight that our kinase inhibitors are attractive candidates for the treatment of GBM.
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Gormen, Meral. "Synthesis Of Ferrocenyl Substituted Pyrazoles." Master's thesis, METU, 2005. http://etd.lib.metu.edu.tr/upload/3/12606358/index.pdf.
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Pyrazoles have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess. The incorporation of the essential structural features of pyrazoles with a ferrocene moiety could provide new derivatives with unexpected and/or enhanced biological activities since several ferrocene derivatives have already been shown to be active against a number of tumors. For this reason, we investigated the synthesis of ferrocenyl-substituted pyrazoles, such as 1-alkyl/aryl-5-ferrocenylpyrazoles, by employing the reaction between (2-formyl-1-chlorovinyl)ferrocene and hydrazine derivatives. Although this reaction is known, it was not studied in much detail and the low yields of ferrocenyl pyrazoles were obtained. Thus, we have reinvestigated this reaction and improved the yields of pyrazoles by optimizing the reaction conditions. (2-Formyl-1-chloro vinyl)ferrocene was first reacted with the excess amount (3 equivalents) of hydrazine derivative at 25 0C in dioxane under argon for 2 hours, and the resulting mixture was then heated at 100 0C for 6 hours in the same solvent. Under our optimized conditions, these reactions afforded 1-alkyl/aryl-5-ferrocenylpyrazole derivatives in moderate to good yields as a single or major product of the reaction. In some cases, 1-alkyl/aryl-3-ferrocenylpyrazole derivatives resulted from these reactions as very minor products.
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Pasin, Juliana Saibt Martins. "Atividade antipirética e antiinflamatória de derivados 5-trifluormetil-4,5-diidro-1H-1-carboxiamida pirazol em ratos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/28004.
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A febre é um aumento regulado da temperatura corporal central, caracterizada por uma alteração no centro termorregulatório, a qual resulta da interação entre o sistema nervoso central e o imunológico. Enquanto a febre caracteriza lesão celular, infecção e inflamação, ela tem sido considerada o mais importante componente da resposta de fase aguda. Embora existam evidências de que a febre aumenta a defesa do hospedeiro, alguns estudos têm sugerido que o aumento da temperatura central a níveis febris pode ser prejudicial. Portanto, nas situações clínicas nas quais os riscos associados com a febre superam os benefícios, o tratamento antipirético é formalmente indicado. Os derivados pirazolínicos constituem um importante grupo de compostos orgânicos que têm sido extensivamente estudados devido às suas inúmeras atividades biológicas, que incluem atividade antipirética. Recentemente uma série de derivados pirazolínicos inéditos foi avaliada quanto à atividade antiedematogênica e antinociceptiva em camundongos. Estes compostos causam antinocicepção no teste da formalina e no modelo de artrite induzida por adjuvante de Freund, bem como diminuem o edema induzido por carragenina. Dados os efeitos antiinflamatórios descritos para estes compostos, o objetivo do estudo foi investigar o efeito de oito derivados 5-trifluormetil-4,5-diidro- 1H-1-pirazol-1-carboxiamida (TFDPs) sobre a temperatura corporal basal, a febre induzida por S. cerevisiae (0.135 g/Kg, i.p.) e a inflamação peritoneal em ratos Wistar machos de 28 dias de idade. Somente os compostos 3Et- e 3Pr-TFDP (140 e 200 μmol/kg respectivamente, s.c., 4 h após a injeção do S. cerevisiae) atenuaram a febre em 61.0% e 82.4%, respectivamente. Estes dois compostos foram selecionados para a investigação dos mecanismos de ação. Os efeitos sobre a atividade da ciclooxigenase-1 e -2 (COX-1 e COX-2), a oxidação in vitro do 1,1-difenil-2- picrilhidrazil (DPPH), os níveis de TNF-a e IL-1b e influxo de leucócitos na cavidade peritoneal dos ratos injetados com S. cerevisiae foram determinados. Enquanto 3Et- e 3Pr-TFDP não alteraram o aumento nos níveis de TNF-a e IL-1b induzido por S. cerevisiae, o derivado 3Et- TFDP causou uma redução de 42% na contagem de leucócitos na cavidade peritoneal. 3Et- e 3Pr-TFDP não alteraram a atividade da COX-1 e COX-2 in vitro, mas apresentaram atividade antioxidante no ensaio do DPPH, com CI50 de 39.3 (25.0-62.0) mM e 162.9 (135.6-195.7) mM, respectivamente. Em outro grupo de experimentos, foi avaliado o efeito do pré-tratamento dos animais com os compostos 3Et- e 3Pr-TFDP sobre a inflamação peritoneal induzida por S.cerevisiae em ratos. O pré-tratamento com 3Et-TFDP (140 μmol/kg, 5 mL/Kg, s.c.) preveniu significativamente o aumento no influxo de leucócitos, a permeabilidade vascular peritoneal e a atividade da mieloperoxidase (MPO), mas não teve efeito sobre os níveis de TNF-a e IL-1b. Por outro lado, 3Pr-TFDP (200 μmol/kg, 5 mL/Kg, s.c.) não apresentou efeito sobre nenhum desses parâmetros inflamatórios. O presente estudo descreve dois novos derivados pirazolínicos com atividade antipirética, cujos mecanismos de ação não envolvem inibição da COX ou inibição da liberação de citocinas pirogênicas. Além disso, foi demonstrado que o composto 3Et-TFDP apresenta potencial antiinflamatório, atuando sobre o influxo de leucócitos, permeabilidade vascular peritoneal e aumento da atividade da MPO induzidos por S. cerevisiae. Em conjunto, nossos dados sugerem que os derivados pirazolínicos 3Et- e 3Pr-TFDP parecem ser compostos antipiréticos e antiinflamatórios promissores.Fever is a regulated increase of body core temperature characterized by a raised thermoregulatory set point, which results from the interaction of the central nervous and immune systems. While fever is a hallmark of injury, infection and inflammation, it has also been considered the most important component of acute-phase response. Although there is evidence supporting the idea that fever enhances host defenses, some studies have suggested that raising core temperature to the febrile range may be harmful. Therefore, in the clinical situations in which fever-associated risks outweigh benefits, antipyretic treatment is formally indicated. Pyrazoles constitute an important group of organic compounds that have been extensively studied due to their numerous biological activities. Recently a series of pyrazole derivatives have been screened for antinociceptive and antiedematogenic activity in mice. These compounds cause antinociception in the formalin test and in the Freund's adjuvant (CFA) animal model of arthritis and decrease carrageenin-induced edema. Given the effects reported for these compounds, we decided to investigate the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro- 1H-1-carboxyamidepyrazoles (TFDPs) on body temperature, baker´s yeast-induced fever and peritoneal inflammation in 28 days-old male Wistar rats. Only 3ethyl- and 3propyl-TFDP (140 and 200 μmol/kg, respectively, s.c., 4 h after S. cerevisiae injection) attenuated baker’s yeastinduced fever by 61.0% and 82.4%, respectively. These two effective antipyretics were selected to investigate the mechanisms of action. The effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities, on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on TNF-a and IL- 1b levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast were determined. While 3ethyl- and 3propyl-TFDP did not reduce baker’s yeastinduced increases of IL-1 or TNF- levels, 3ethyl-TFDP caused a 42% reduction in peritoneal leukocyte count. 3ethyl- and 3propyl-TFDP did not alter COX-1 and COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39.3 (25.0-62.0) mM and 162.9 (135.6-195.7) mM, respectively. In a other set of the experiments, we investigate the effect of 3- ethyl- and 3-propyl-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles on S.cerevisiae-induced peritoneal inflammation in rats. Pre-treatment with 3ethyl-TFDP (140 μmol/kg, 5 mL/Kg) significantly prevented S.cerevisiae-induced increase in leukocyte influx, peritoneal vascular permeability and myeloperoxidase activity, but had no effect on TNF-a and IL-1b levels. On the other hand, 3propyl-TFDP (200 μmol/kg, 5 mL/Kg) had no effect on these inflammatory parameters. The current study describes two novel antipyretic pyrazole derivatives, whose mechanisms of action do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release. In addition, it is shown that 3ethyl-TFDP presents antiinflammatory potential, since it reduces leukocyte influx, peritoneal vascular permeability and MPO activity. Taken together, our data suggest that the pyrazole derivatives 3ethyl- and 3propyl-TFDP seems a promising antipyretic and anti-inflammatory compounds.
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Crotti, Simone. "Computer assisted synthesis and in-vitro cytotoxic evaluation of new pyrazole-fused isoquinolinoquinones derivatives as PI3K receptor antagonist with promising antitumoral activity." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/11206/.
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The importance of pyrazole and isoquinoline-5,8-dione scaffolds in medical chemistry is underlined by the high number of drugs currently on trading that contains these active ingredients. Due to their cytotoxic capability, the interest of medicinal chemists in these heterocyclic rings has grown exponentially especially, for cancer therapy. In this project, the first synthesis of pyrazole-fused isoquinoline-5,8-diones has been developed. 1,3-Dipolar cycloaddition followed by oxidative aromatization, established by our research group, has been employed. Screening of reaction conditions and characterization studies about the regioselectivity have been successfully performed. A remote control of regioselectivity, to achieve the two possible regioisomers has been accomplished. Through Molecular Docking studies, Structure-Activity relationship of differently substituted scaffolds containing our central core proved that a family of PI3K inhibitors have been discovered. Finally, in order to verify the promising antitumor activity, a first test of cell viability in vitro on T98G cell line of a solid brain tumor, the Glioblastoma Multiforme, showed cytotoxic inhibition comparable to currently trade anticancer drugs.
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Moura, Soraia Santana de. "Avaliação da toxicidade aguda e subaguda de um novo protótipo candidato a fármaco cardiovascular." Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tede/6958.
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Fundação de Apoio à Pesquisa - FUNAPE
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Financiadora de Estudos e Projetos- Finep
Cardiovascular diseases are among the diseases of higher mortality rates in Brazil and worldwide . In contrast, it is reducing deaths of cardiovascular diseases due, in large part, to the production of drugs that can control their risk factors, but the wide reporting of side effects and contraindications persist and interfere negatively in the context of mortality these diseases. In this point, it is necessary to develop new drugs more effective and safer. The process of development of new drug requires numerous preclinical studies that generate information regarding safety profile in vivo determinants for making the decision to start clinical trials. Although it is a conventional practice, the use of animals in scientific research should happen consciously, always considering the ethical issues of animal experimentation. In this study, we investigated the basal cytotoxicity against 3T3 cells of seven pyrazole compounds (LQFM011, LQFM012, LQFM020, LQFM021, LQFM022, and LQFM023 LQFM024) and classified then in GHS system. Whereas the compound LQFM021 proved to be the most effective in the tests performed in parallel pharmacodynamic study, we investigated whether acute oral toxicity, subacute and mutagenicity of this compound. The results showed that the compounds have low cytotoxicity profile in basal cell line (3T3). The estimated LD50 values for compounds LQFM011, LQFM012, LQFM020, LQFM021, LQFM022, and LQFM023 LQFM024 were 548, 551, 568, 533, 457, 482, 565 mg / kg, respectively. The compounds LQFM020, LQFM023 LQFM024 were classified in category 5 GHS system and LQFM021 was classified in category 4. The subacute toxicological research for 28 days LQFM021 the compound showed that this compound did not affect the metabolic, hematological and biochemical animal parameters in any of the doses of exposure However, the histopathology indicated hepatotoxic and nephrotoxic potential of this compound and interference in the process of hematopoiesis, but did not indicate mutagenic potential. . Given the above, we conside
As doenças cardiovasculares estão entre as doenças de maior letalidade no Brasil e no mundo. Em contrapartida, vê-se um quadro redução das mortes atribuídas às enfermidades cardiovasculares devido, em grande parte, à produção de medicamentos capazes de controlar seus fatores de risco, porém, o vasto relato de efeitos colaterais e contraindicações persistem e interferem negativamente no quadro de morbimortalidade dessas doenças. Neste sentindo, é imprescindível buscar novos fármacos mais efetivos e seguros. O processo de desenvolvimento de um novo fármaco exige numerosos estudos pré-clínicos que geram informações quanto ao seu perfil de segurança in vivo, determinantes para a tomada de decisão de se iniciar os estudos clínicos. Embora seja uma prática convencional, o uso de animais em pesquisas científicas deve ocorrer de forma consciente, considerando sempre as questões éticas de experimentação animal. Neste trabalho, investigou-se a citotoxicidade basal frente as células 3T3 de sete compostos pirazolínicos (LQFM011, LQFM012, LQFM020, LQFM021, LQFM022, LQFM023 e LQFM024) e suas classificações no sistema GHS. Considerando que o composto LQFM021 demonstrou ser o mais eficaz nos ensaios realizados em paralelo de farmacodinâmica, investigou-se toxicidade oral aguda, subaguda e mutagenicidade do composto. Os resultados mostraram que os compostos possuem perfil de baixa citotoxicidade em linhagem basal (3T3). Os valores de DL50 estimados para os compostos LQFM011, LQFM012, LQFM020, LQFM021, LQFM022, LQFM023 e LQFM024 foram 548, 551, 568, 533, 457, 482, 565 mg/kg, respectivamente. Os compostos LQFM020, LQFM023 e LQFM024 foram classificadas na categoria 5 do sistema GHS e o composto LQFM021 foi classificado na categoria 4. A investigação toxicológica subaguda por 28 dias do composto LQFM021 mostrou que este composto não interferiu nos parâmetros metabólico, hematológico e bioquímico dos animais em nenhuma das doses de exposição. No entanto, o estudo histopatológico indicou potencial nefrotóxico e hepatotóxico deste composto e interferência sobre o processo de hematopoiese, entretanto, não apresentou potencial mutagênico. Diante do exposto, consideramos que o composto LQFM021 apresenta um baixo perfil de toxicidade e os estudos de continuidade devem ser encorajados.
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Chandanshive, Jay Zumbar <1983>. "Regiocontrolled Synthesis of Pyrazole Derivatives Through 1,3-Dipolar Cycloaddition Reaction And Synthesis of Helicene-Thiourea based and Polymer Supported Soos's Catalyst for Asymmetric Synthesis." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5826/1/Chandanshive_JAY_ZUMBAR_Thesis.pdf.
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In first part we have developed a simple regiocontrolled protocol of
1,3-DC to get ring fused pyrazole derivatives. These pyrazole derivatives were synthesized using
1,3-DC between nitrile imine and various dipolarophiles such as alkynes, cyclic α,β-ketones,
lactones, thiocatones and lactums. The reactions were found to be highly regiospecific.
In second part we have discussed about helicene, its properties, synthesis and applications
as asymmetric catalyst.Due to inherent chirality, herein we have made an
attempt to synthesize the helicene-thiourea based catalyst for asymmetric catalysis. The synthesis
involved formation of two key intermediates viz, bromo-phenanthrene 5 and a vinyl-naphthalene
10. The coupling of these two intermediates leads to formation of hexahelicene.
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Chandanshive, Jay Zumbar <1983>. "Regiocontrolled Synthesis of Pyrazole Derivatives Through 1,3-Dipolar Cycloaddition Reaction And Synthesis of Helicene-Thiourea based and Polymer Supported Soos's Catalyst for Asymmetric Synthesis." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5826/.
Full textAbstract:
In first part we have developed a simple regiocontrolled protocol of
1,3-DC to get ring fused pyrazole derivatives. These pyrazole derivatives were synthesized using
1,3-DC between nitrile imine and various dipolarophiles such as alkynes, cyclic α,β-ketones,
lactones, thiocatones and lactums. The reactions were found to be highly regiospecific.
In second part we have discussed about helicene, its properties, synthesis and applications
as asymmetric catalyst.Due to inherent chirality, herein we have made an
attempt to synthesize the helicene-thiourea based catalyst for asymmetric catalysis. The synthesis
involved formation of two key intermediates viz, bromo-phenanthrene 5 and a vinyl-naphthalene
10. The coupling of these two intermediates leads to formation of hexahelicene.
14
Nesfu, Nadirah Zawani Binti Mohd. "Les études sur les fruits de Momordica charantia et la synthèse de dérivés de benzylidène indanone pyrazolyl substitués comme inhibiteurs de la protéase NS2B/NS3 du virus de la dengue de type 2." Electronic Thesis or Diss., Université de Lorraine, 2020. http://www.theses.fr/2020LORR0092.
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Il n'existe pas de thérapies curatives ou préventives de la dengue (DF). Seuls des soins médicaux complémentaires et une thérapie par les fluides sont disponibles pour lutter contre la dengue. Certains patients optent pour des mesures de prévention et de traitement utilisées par les peuples anciens ou des remèdes populaires pour traiter la maladie. L'un des remèdes populaires utilisés par les patients atteints de dengue à l'hôpital de Malaisie est la consommation de soupe de viande de grenouille au melon amer (Momordica charantia). La chair des fruits et les graines du Momordica charantia (M. charantia) ont été utilisées dans cette étude. L'huile des graines de M. charantia a été extraite par extraction enzymatique aqueuse (AEE) et le rendement en huile a augmenté avec la condition optimale pour extraire l'huile de graines était d'utiliser HEL1:X7 (5:1.25). L'huile de graines ainsi que la teneur en lignine, hémicelullose, sucres solubles et acides uroniques étaient différentes selon le type de cocktail enzymatique. D'autre part, l'extrait d'acétate d'éthyle de la chair du fruit de M. charantia a inhibé 38.11±1.06 % de la DENV-2 protéase NS2B/NS3. Sur la base de l'analyse GC-MS, on a trouvé la trace d'acide gallique et on a sélectionné les cadres structurels de base pour la synthèse de l'inhibiteur de protéase DENV-2 NS2B/NS3. Les dérivés de l'indanone substituée par le pyrazolyle, 90a-t, ont été synthétisés et caractérisés par analyse FTIR, RMN et LC-MS. Un pourcentage approprié de rendement des composés a été obtenu. Les composés 90a-t ont été soumis à une étude in silico en utilisant AutoDock4.2 pour identifier le mode de liaison et la conformation avec la structure cristalline de la protéine d'homologie de Wichapong. Cinq composés ont obtenu une énergie libre de liaison (FEB) inférieure à -7.55 kcal/mol. Le composé 90p a montré huit interactions de liaison hydrogène, une interaction d'empilement π-π, et une interaction π-alkyle avec le résidu d'acide aminé dans la DENV-2protéase NS2B/NS3. Enfin, les études in vitro des cinq principaux composés synthétisés par ancrage vers la DENV-2 protéase NS2B/NS3 en utilisant le substrat peptidique fluorogène Boc-Gly-Arg-7-amino-4-méthylcoumarine ont été menées. La panduratine A a été utilisée comme témoin positif. Le composé 90p a montré une forte activité d'inhibiteur de la DENV-2 protéase NS2B/NS3 (65.61±0.98 %), tandis que la panduratine A (47.59±1.03 %) et l'acide gallique (25.11±1.11 %) ont été utilisés comme témoins positifs. La valeur de la CI50 pour le composé 90p a été observée à 78.87 µM, ce qui est inférieur à la valeur de 290.27 µM pour la panduratine A. Le composé 90p est considéré comme un puissant composé de type "hit-to-led" dans le développement de l'inhibiteur de DENV-2 protéase NS2B/NS3There are neither curative nor preventive therapies of dengue fever (DF). Only supplemental medical care and fluid therapy are available to fight DF. Some patients opt for prevention and treatment measure used by the ancient people or folk remedy to treat sickness. One of folk remedy used among patients with dengue fever in the Malaysia hospital is consumption of frog meat soup with bitter melon (Momordica charantia). The fruits flesh and seeds of Momordica charantia (M. charantia) were utilized in this study. The oil of M. charantia seeds were extracted via aqueous enzymatic extraction (AEE) and the oil yield increased with optimum condition to extract the seed oil was to use HEL1:X7 (5:1.25). The seeds oil as well as the lignin, hemicelullose, soluble sugars, and uronic acids content were different accordance to the type of enzyme cocktail ratio. On the other hand, the M. charantia fruits flesh ethyl acetate extract was found to inhibit 38.11 ± 1.06 % of the DENV-2 NS2B/NS3 protease. Based on the GC-MS analysis the trace of gallic acid was found and was selected the basic structural frameworks for synthesis of the DENV-2 NS2B/NS3 protease inhibitor. The pyrazolyl substituted indanone derivatives, 90a-t were synthesized and characterized using FTIR, NMR, and LC-MS analysis. An appropriate percentage of yield of the compounds were obtained. The compounds 90a-t underwent in silico study using AutoDock4.2 to identify the binding mode and conformation with the Wichapong homology protein crystal structure. Five compounds were found to obtained free energy of binding (FEB) less than -7.55 kcal/mol. Compound 90p showed eight hydrogen bond interactions, one π-π stacking interaction, and one π-alkyl interaction with the amino acid residue in the DENV-2 NS2B/NS3 protease. Lastly, the in vitro studies of top five docked synthesized compound towards DENV-2 NS2B/NS3 protease by using fluorogenic peptide substrate Boc-Gly-Arg-7-amino-4-methylcoumarin were conducted. The panduratin A was used as the positive control. Compound 90p showed a high DENV-2 NS2B/NS3 protease inhibitor activity (65.61 ± 0.98 %), while panduratin A (47.59 ± 1.03 %), and gallic acid (25.11 ± 1.11 %). The IC50 value for compound 90p was observed to be 78.87 µM which is lower compared to the panduratin A, 290.27 µM. The compound 90p is concluded to be a potent hit-to-led compound in the development of DENV-2 NS2B/NS3 protease inhibitor
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Xu, Zhan-Zhong, and 許占中. "Synthesis of azamerocarbocyanine dyes from pyrazolone derivatives." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/48609096380898483033.
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Chung, Shi Chan, and 許占中. "Synthesis of azamerocarbocyanine dyes from pyrazolone derivatives." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/64588963452708359594.
Full textAbstract:
碩士國立臺灣科技大學
纖維及高分子研究所
86
The pyrazolone derivatives were prepared by the reaction of ethyl acetoacetatewith hydrazine hydrate,methylhydrazine and phenylhydrazine,respectively.Theazamerocarbocyanine dyes were synthesised from pyrazolone intermediates and1,3,3-trimethyl-2-methylene indoline.The structure of the dyes was confirmedby E.A,IR,MS,H-NMR spectral analysis.Azamerocarbocyanine dyes were applied to dying on polyester fabrics and shown red to reddish-purple hues.The sublimation and light fastness of dyes on pol-yester fabrics were measured and shown in the range among 3-5 grade and 3-7grade,respectively.The photofading rate of the dyes shown 1 and 2 order respectively.
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ATZORI, ELENA MARIA. "Design, synthesis and antiviral evaluation of pyrazole and pyrazoline derivatives as novel inhibitors of flavivirus and pestivirus replication." Doctoral thesis, 2017. http://hdl.handle.net/11573/931038.
Full textAbstract:
The Flaviviridae family represents a large group of viral pathogens which are divided, according to the current taxonomy, in four genera: Flavivirus (type spe¬cies, yellow fever virus (YFV)), Hepacivirus (type species, hepatitis C virus (HCV)), Pestivirus (type species, bovine virus diar¬rhea (BVDV)) and Pegivirus (type species, hepatitis G virus (HGV)). Despite the majority of these viruses are responsible for a wide range of severe diseases in humans and animals, specific antiviral therapies are currently available only for the treatment of HCV infections. The global, social and economic impact due to morbidity and even mortality associated with these infections, urgently demands effective therapeutic interventions.
Following the researches undertaken in our laboratory on heterocyclic compounds with antiviral activity, the design, synthesis and antiviral evaluation of new classes of pyrazole and pyrazoline derivatives with potent and selective anti-Flavivirus or anti-BVDV activity is described in the present PhD thesis.
By the antiviral screening of an in house library of compounds, N-(1,3-diphenyl-1H-pyrazol-4-yl)methyl]anilines were identified as a new class of potent and selective inhibitors of human respiratory syncytial virus (RSV) replication. Some derivatives were also endowed with a moderate activity against BVDV and against significant human pathogens belonging to the Flavivirus genus such as YFV, Dengue Virus (DENV) and West Nile Virus (WNV). The hit compounds exhibited activity in the micromolar range coupled with low cytotoxicity (CC50 > 100 µM) against the cell lines (MDBK and BHK-21) utilized for the in vitro assays. Therefore, the systematic modification of all the portions of the molecular scaffold was planned, in order to identify more active compounds and to maintain the low cytotoxicity of the hit compounds. In particular, potent and selective inhibitors of YFV replication were obtained by replacement of the 1-phenyl ring with the 1-phenylsulfonyl moiety.
Pursuing our research on anti-Flaviridae compounds, we also devoted our attention to pyrazoline analogues of previously studied pyrazole derivatives. The antiviral screening of the novel series of 1,3,5-trisubstituted pyrazolines has led to the identification of new hit compounds with promising activity against YFV and BVDV.
Time of addition experiments were performed to determine the possible step(s) in YFV replication cycle that is inhibited by two 1,3,5-triphenyl-pyrazolines selected for their high anti-YFV potency and selectivity. The results of these studies showed that both compounds exhibited maximal inhibition when added in the pretreatment of BHK-21 cells or during infection of cell cultures with YFV. A similar behavior was observed for the reference inhibitor 6-Azauridine, at higher concentrations. However, further investigations are necessary for the identification of the anti-YFV target of these pyrazoline derivatives.
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Yu-TsungLiu and 呂侑聰. "Novel Pyrazole Derivatives for Treating Osteoporosis." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/ew9k4v.
Full textAbstract:
碩士國立成功大學
生物化學暨分子生物學研究所
106
Osteoporosis is known as an age-related disease that result from an imbalance between the generation and decomposition of the bone matrix. It is caused by either the degeneration of osteoblasts leading to weaker bone forming activity or the promotion of osteoclasts increasing bone resorption activity. To treat osteoporosis, several drugs are available now. However, there are still some drawbacks of the drugs such as many side effects and high cost. According to the situation, we would like to research and synthesize new compounds to treat osteoporosis. 3-(5’-Hydroxymethyl-2’-furyl)-1-benzyl indazole (YC-1) (1) is a pyrazole derivative that has been demonstrated with many potent biological and pathological activities. YC-1 was also exhibited anti-osteoporosis effects through promoting cGMP by activating sGC, and then reducing osteoclast activity and inducing osteoblast activity. According to the above-mentioned feature, many YC-1 derivatives had been synthesized with different side chains to study structure-activity relationship. Among them, 2-(dimethylamino)ethyl group showed obvious inhibition of osteoclast both in vitro and in vivo. However, previous researches did not include variable side chains; therefore, there is still much room for new YC-1 derivatives to figure out structure-activity relationship (SAR) of YC-1 derivatives. In this study, we would like to synthesize novel YC-1 derivatives that are effective in treating osteoporosis without many side effects and high cost. Based on the previous research, we modified the side chains on indazole, such as replacement of the furan with pyridine and thiophene. On the other hand, we also transformed the 1-benzyl group with 3-fluorobenzyl group. Then, we characterized the compound structures with 1H and 13C NMR to check that three target compounds were synthesized successfully.
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Dash, Binay Kumar. "Microwave assisted pyrazole derivative synthesis." Thesis, 2007. http://ethesis.nitrkl.ac.in/4365/1/d.pdf.
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In the past few decades, many significant advances in organic chemistry, such as the novel synthetic reagents and methods, as well as the advent of an array of analytical apparatus and techniques, have made the organic synthesis more dynamic and effective than ever before. However, the practical aspects for carrying out laboratory-scale reactions have changed little during this period. Especially when heating is necessary, oil baths and heating jackets are the main equipment used. These traditional heating techniques are slow and time-consuming, and sometimes can lead to overheating and decomposition of the substrate and product. To this end, microwaves have been employed in organic chemistry to reduce the reaction times from hours to minutes, to increase yields and selectivity1.
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Tsai, Meng-Ju, and 蔡孟儒. "Design and Synthesis of 1,3-Diaryl Pyrazole Derivatives." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/4v24x2.
Full textAbstract:
碩士高雄醫學大學
醫藥暨應用化學研究所
102
In recent years, with the evolution of bacteria and abuse of antibiotics, bacteria’s resistance to drugs becomes an important issue in the chemotherapy. Therefore, search for newer and stronger antibiotics are becoming more and more urgent. The present research describes preparation and evaluation of certain novel agents by using 1,3 - diaryl pyrazole as a core structure, introducing various substituent on the C-4 position and the para position of the C-1 aromatic ring. These compounds were evaluated in vitro against S.aureus. Results indicated that rhodanine substituted at C-4 and a fluoro group substituted at the para position of the C-1 aromatic ring is the most favorable in which compound 13b exhibited the strongest antibacterial activity.
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Chen, Tsai Pi, and 蔡弼丞. "Synthesis and Characterization of pyrazolo[1,5-a] Pyrimidine Derivatives." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/73267789211679603689.
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碩士國立臺灣科技大學
高分子工程系
92
ABSTRACT In this study, 4-arylazo-3,5-diaminopyrazole compounds have been synthesized by reaction of arylazomalononitrile with hydrazine hydrate. The symmetrical and asymmetrical 3,6-diarylazo-2,5,7- triaminopyrazolo[1,5-a]pyrimidine heterocyclic disazo dyes have been prepared by the cyclization of 4-arylazo-3,5-diaminopyrazoles with different arylazomalononitriles. The solvatochromic behaviour of these disazo dyes in various solvents was evaluated. The structures of these compounds were determined by spectrometry（UV、FT-IR、1H-NMR）and element analysis（EA）.
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Ke, Fang-Ying, and 柯方盈. "Studies on the Syntheses of Pyrazoline､Thiazoline Derivatives and their Antimicrobial､Antioxidative Activity." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/06836031465387714444.
Full textAbstract:
碩士南台科技大學
化學工程系
91
Many heterocyclic compounds have been known for special physiological activity. Therefore, sydnonyl-substituted pyrazolines, thiazolines and thiazolidines were synthesized in this study. The text is divided into two parts: In the first part, the sydnonyl-substituted pyrazoline derivatives were prepared successfully through the reactions of sydnonyl-substituted α, β-unsaturated ketones and hydrazine hydrate. The new series of sydnonyl-substituted pyrazolines were evaluated for their antimicrobial activity. The results indicated that the antifungal activity of these compounds exhibited more potence then antibacterial activity. In the second part, 3-aryl-4-formylsydnone thiosemicarbazones reacted with cyclic reagents, such as ethyl chloroacetate, ethyl 2-chloroacetoacetate and 2-bromoacetophenone to give heterocyclic substituted sydnones that possess 4-oxo-thiazolidine, thiazoline groups. The synthesized compounds were evaluated for the antioxidant activities. The results indicated that almost all the newly synthesized compounds exhibit significant scavenging effects on DPPH (α,α-diphenyl-β-picrylhydrazyl) free redical. Among these compounds, 4-phenyl-2-[(3-arylsydnon-4-yl-methylene)hydrazono]-2,3-dihydrothiazoles possess the potent radical scavenging activities comparable with that of vitamin E.
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Chun-YenChen and 陳俊言. "Development of New Synthetic Methodologies for Guanidine and Pyrazole Derivatives." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/80255199794902181722.
Full textAbstract:
博士國立成功大學
化學系碩博士班
98
The guanidinium group is present in many natural and synthetic biologically active compounds. Due to its broad spectrum of activity, the guanidine unit has been intensively studied as a synthetic goal and a diversity of new methods has been developed. Cyanamides are important precursors in the synthesis of guanidines. They also exhibit apparent tumor growth inhibition activity. Many of reagents are developed as a cyano cation (CN+) agent to synthesize the cyanamide products. Although their syntheses are straightforward, they do not produce quantitative yields and require tedious purification procedures. Herein, we report a transformation method of isothiocyanates to cyanamides using the commercially available alkali amide NaN(SiMe3)2. Additionally, we expanded the reaction to one pot synthesis of guanidines hydrochloride by using catalyst. Screening data indicated that several compounds exhibited significant in vitro activities against numerous human tumor cell. Pyrazoles are an important family of heterocyclic compounds due to their wide range of pharmacological proprieties. In particular, modified pyrazoles are also the basis of various active material. For this reason, we report the use of palladium chloride in the presence of triphenylphosphine to remove the halogen atom in pyrazoles. The reaction went rapidly and efficiently. Finally, we have developed a new and efficient copper-catalyzed C-N bond formation for 5-aminopyrazoles with arylhalides. The reaction conditions for the copper-mediated N-arylation of heteroarylamines were optimized. The desired compounds of N-monoarylation or N-diarylation of 5-aminopyrazoles were synthesized in different reaction conditions.
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Carreira, Ana Rita Futre. "Synthesis and evaluation of novel pyrazole derivatives for cytotoxic activity." Master's thesis, 2018. http://hdl.handle.net/10773/24248.
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The growing number of cancer patients worldwide has led the scientific community to strengthen research efforts in this field. The development of novel drug candidates for cancer treatment has been largely studied. Among these, pyrazoles derivatives are a promising class for their wide range of pharmacological activities, including antitumoral action.
This work describes the preparation of (E)-3(5)-(2-hydroxyphenyl)-4-styryl-1H-pirazole derivatives, either by glycosylation reactions or by the formation of ruthenium trithiacyclononane complexes. The new compounds aim at having antitumoral activity. Full characterization of the compounds is carried out by NMR 1D (1H and 13C) and 2D (HSQC, HMBC, COSY and NOESY) spectroscopies and by mass spectrometry. The new ruthenium-pyrazoles are also studied by infrared spectroscopy. Whenever appropriate, the purity of the synthesized compounds is evaluated by melting point measurements.
The compounds are evaluated against a gastric cancer cell line (AGS) and against a lung fibroblast cell line (MRC-5) to roughly assess their selectivity. The most potent compound is the ruthenium complex with the pyrazole having a -para-OCH3 substituted styryl. This compound features an IC50 value of 18.3 μM against the cancer cell line AGS and an IC50 value of 62.2 μM on the healthy cell line MRC-5. Furthermore, the selectivity of this complex with this ligand is higher in comparison to that of ligand aloneO número crescente de pessoas afetadas mundialmente pelo cancro tem levado a comunidade científica a ampliar os esforços de pesquisa nesta área. O desenvolvimento de novos fármacos com potencial aplicação no tratamento do cancro tem sido amplamente estudado. Os pirazóis e os seus derivados são uma classe promissora devido ao seu variado espectro de atividades, que inclui a ação anticancerígena. Neste trabalho são preparados derivados de uma família de (E)-3(5)-(2-hidroxifenil)-4-estiril-1H-pirazóis através de reações de glicosilação ou pela formação de complexos de coordenação de ruténio tritiaciclononano, com o objetivo de obter novos compostos com ação citotóxica contra células tumorais. Os compostos sintetizados são caracterizados recorrendo a técnicas espetroscópicas de RMN 1D (1H e 13C) e 2D (HSQC, HMBC, COSY e NOESY), espectrometria de massa e espectroscopia de infravermelho no caso dos complexos de ruténio. Sempre que possível, a pureza dos compostos foi ainda avaliada através da determinação do ponto de fusão. Os compostos sintetizados são avaliados contra uma linha celular de cancro do estômago (AGS) e contra uma linha celular saudável de fibroblastos do pulmão (MRC-5), de modo a averiguar tangencialmente a sua seletividade. Dos compostos sintetizados, o mais potente é o complexo de ruténio contendo o ligando pirazol com um grupo metoxilo na posição -para- do estirilo. Este composto apresentou um IC50 de 18.3 μM contra a linha celular tumoral AGS e um IC50 de 62.2 μM contra a linha celular saudável MRC-5. A inserção do ligando no complexo de ruténio melhorou a seletividade quando comparada com o ligando isolado
Mestrado em Bioquímica
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Chiou, Yu-Ting, and 邱昱婷. "Efficient Synthesis of Pyrazole Derivatives in a Continuous Flow System." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/63872017113267319198.
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碩士高雄醫學大學
醫藥暨應用化學系碩士班
105
Ynones are considered as highly reactive molecules and have been widely used in modern synthetic organic chemistry. There are various methods for synthesis of ynones which usually take a long time. The feature with continuous flow system is to derive desired compound in a very short period due to the unstable reactive intermediate being able to transferred to another location before their decomposition and allowed to react with another reactive reagent. Thus, the synthesis of pyrazole from phenylacetylene or the derivatives as the starting materials, which will be deprotonated by n-butyllithium to form ynones with anhydride derivatives and successively with the addition of hydrazine via microfluidic devices will be described in this work. Furthermore, the system could be carried out under ambient temperature or subzero Celsius degree and gain the expected products efficiently with moderate to high yields.
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Wang, Li-Ya, and 王麗雅. "Synthesis of 1,2,4-triazole and pyrazole derivatives and biological activity study." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/20653168332065861292.
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Liu, Wei-Hsin, and 劉瑋鑫. "Dye-sensitized Solar Cell Based on Pyrazolate Ru(II) Complexes and Triphenylamine Derivatives." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/94741096946004249987.
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博士國立臺灣大學
化學研究所
96
Chapter 1~2. New Family of Ruthenium-Dye-Sensitized Nanocrystalline TiO2 Solar cell A new series of ruthenium complexes with tridentate bipyridine-pyrazolate ancillary ligands has been synthesized in an attempt to elongate the π-conjugated system as well as to increase the optical extinction coefficient, possible dye uptake on TiO2 and photostability. As for the DSSC application, it was found that the complexes possess highly conversion efficiency under standard AM 1.5 irradiation (100 mW cm-2). Chapter 3. Strategic Design and Synthesis of Novel Trident Bipyridine Pyrazolate Coupled Ru(II) Complexes to Achieve Superior Solar Conversion Efficiency A new series of trident bipyridine pyrazolate coupled Ru(II) complexes CK7, CK9, HYH052 and HYH060 were strategically synthesized. In comparison to N719, CK7 and HYH060 achieved the original proposal of gaining absorption extinction coefficient ranging from 350 to ~550 nm, accompanied by lowering of the lowest lying energy gap. These advantages allow us to reduce the thickness of TiO2 layer, resulting in great suppress of dark current and hence increase of Voc. Upon optimization, HYH060 has attained η= 8.07, Jsc= 15.8 mA cm-2, Voc = 753 mV and FF = 0.678, the results of which are superior to that of N719 prepared in this study. Chapter 4. Simple Organic Molecules Bearing 3,4-Ethylene dioxythiophene Linker for Efficient Dye-Sensitized Solar Cells 3,4-Ethylenedioxythiophene and bis[2-(2-methoxyethoxy) exthoxy]thiophene bridged donor-acceptor molecules LJ1 ~ LJ4 for dye-sensitized solar cells have been synthesized, among which LJ1 achieved a solar-to-energy conversion efficiency of 7.3%, compared to 7.7% optimized for N719 dye
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Kuo, Ting-Hao, and 郭廷濠. "Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/02135079789878535306.
Full textAbstract:
碩士國立臺灣大學
藥理學研究所
103
As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2- (dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclast’s early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.
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Tsai, Shao-Ling, and 蔡韶玲. "β-Diketone, Pyrazole and Isoxazole Derivatives with Polar Groups: Liquid Crystalline and Thermodynamic Properties." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/66543881468988295014.
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碩士國立中央大學
化學研究所
95
In this serie, we report the synthesis, characterization and mesomorphic properties of two series of new mesogenic derivatives based on pyrazole and isoxazole structures. All compounds were characterized by 1H, 13C-NMR spectroscopy and elemental analysis. The phase behaviors of these mesogenic compounds were characterized and studied by differential scanning calorimeter (DSC) and polarization optical microscope. In serie one, a new type of mesogenic compounds derived from heterocyclic pyrazole and isoxazole (Iz-Cn) were prepared and studied. All compounds exhibited smectic phases depending on the carbon length attached. Replacing hydrogen atom of pyrazole by methyl group (Mpz-Cn), ethanol group (Epz-Cn) and pyridinal group (Ppz-Cn) were carried out and the mesomorphic behavior studied. In serie two, we designed and characterized a series of asymmetrical of organic molecules Hpz-Cn-OH derived from pyrazole with one side chains. These compounds exhibited smectic phases.
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Chang, En-Ming, and 張恩銘. "Development and Application of Pyrazole Derivatives in Medicinal Syntheses and Organic Light-Emiting Diodes." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/77416158491514837742.
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博士國立成功大學
化學系碩博士班
96
In this thesis, we developed the new synthesis and application for pyrazole-based derivatives as the DHODase inhibitors, and the organic electronic-transporting and electronic-hole electroluminescent materials derivatives. In the first part, we developed a new efficient and convenient synthetic method from 3-(p-aryl)-4-cyanosydnone for Pyrazole-based DHODase inhibitors via chemoselective 1,3-diploar cycloaddition, amidation, and Ritter reaction. Overall yields was in 51–60% yield in three steps. In the second part, 1,3,4-oxadiazole-based pyrazole derivatives have been synthesized and characterized as blue-greenish electroluminescent materials. Those compounds are successfully inducted a pyrazole chromophore and multiple 1,3,4-oxadiazole moieties by 1,3-dipolar-cyclization and dehydration-cyclization to promote the conjugation range and exhibit high thermal stability and good physical properties. Spectroscopic studies, the measurements of cyclic voltammogram, thermal characterization and electroluminescent properties have revealed that 1,3,4-oxadiazole-based pyrazole derivatives are efficient blue-greenish electroluminescent materials In the third part, we have also prepared the double-layer OLED devices containing new organic electronic-transporting and electronic-hole electroluminescent materials under vacuum onto the ITO-coated glass substrate. The device showed the blue-greenish emission.
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Zhong, Ren Hua, and 鍾仁華. "Studies on the reaction of ��-chloroformylarylhydrazine hydrochloride with pyrazole, imidazoles and 1,2,4-triazoles derivatives." Thesis, 1996. http://ndltd.ncl.edu.tw/handle/85706865936867611512.
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Lin, Chi-Jen, and 林祺臻. "Studies on the Synthesis and Light-Emitting Properties of Pyrazole Derivatives Including 1,3,4-Oxadiazole." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/14058259639664843553.
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碩士國立成功大學
化學系碩博士班
93
Organic materials have been expected to be applicable for practical electroluminescent (EL) devices because of their high florescence efficiency and semiconducting properties. One of the most fascinating advantage of organic materials is the possibility of a wide selection of emission colors, particularly in the blue region, in EL displays through molecular design of organic materials. In this study, we explored a series of new blue emission materials. Compounds derived from 1,3,4-oxadiazoles had been reported having good electron-transporting properties and the pyrazole moietie is an electron-rich heterocycle. We established to introduce pyrazole units into the main chain conjugate with two or three 1,3,4-oxadiazole moieties to improve the electroluminiecent properties of 1,3,4-oxadiazole-based pyrazole derivatives by using convenient synthesis strategy. The electroluminiecent properties and thermal stability for the obtained products were studied by analyzing UV-VIS, PL,CV,and DSC spectra. And finally, a double-layer OLED devices were constructed by vapor deposition of the materials under vacuum onto the ITO-coated glass substrate.The I-V curves and EL spectra had proven that our new synthetic compounds were new efficient blue electroluminescent materials.
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Chen, Shiang-Chi, and 陳祥麒. "Microwave-mediated cycloaddition of 1,3-diphenylprop-2-yn-1-one to pyrazole and naphothofuran derivatives." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/27362676310213208760.
Full textAbstract:
碩士國立臺灣師範大學
化學系
103
This thesis is divided into three chapters. The first Chapter illustrates a convenient procedure for the one-pot synthesis of pyrazole derivatives. In this strategy, the initial step is the Michael addition of morpholine to 1,3-diphenylprop-2-yn-1-one to form an intermediate, and followed by the cycloaddition with phenylhydrazine under acidic condition. Here, we disclosed the reaction in traditional heating as well as microwave heating method. Chapter two, discribes the method for the synthesis of pyrazole under “on water” condition, supported by microwave heating method under 150 oC. Chapter three deals with the synthesis of naphthofuran derivatives. This reaction involves two steps. In the first step, the reaction of of 1,3-diphenylprop-2-yn-1-one and 2- naphthol catalyzed by Lewis acid. And the the second step is the intramolecular cycloaddition catalyzed by base and copper(II) reagents to afford naphthofuran derivatives in good yields. Keywords: 1,3-diphenylprop-2-yn-1-one、pyrazole、naphothofuran、Microwave-mediated、one-pot synthesis.
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Sengupta, Satirtha. "Studies on Metal-Organic Frameworks and Metallogels of Pyrazole based ligands and their Amide Derivatives." Thesis, 2019. http://hdl.handle.net/10821/8220.
Full textAbstract:
Metal-organic frameworks (MOFs) or coordination polymers are one, two or three dimensional coordination networks, usually porous, comprising of metal ions linked together with one or more organic ligand or linker molecules having varied applications in the field of gas storage and separation, magnetism, catalysis etc. However there is a subtle difference in the definition of the term coordination polymers and metal organic frameworks. The former merely signifies an extended network formed due to coordination bond between metal and ligand(s) monomers and says nothing about the final structure or morphology. Metal-organic frameworks, on the other hand, should possess a geometrically well-defined structure made through strong covalent or coordinate bonding between the metal and ligand and comprising of units available for post-synthetic modifications. Metal-organic gels (MOGs) or metallogels are special class of supramolecular gels where metal plays an important role in gel formation either through covalent interactions with the ligand giving rise to 3D gel network or forming discrete metallogelators which then self-assemble to form gel via non-covalent interactions immobilising large quantity of solvents with the network. In both cases, the gels formed show metal specific properties such as spectroscopic, catalytic, redox and magnetic properties.Research was carried over under the supervision of Dr. Raju Mondal of Inorganic Chemistry division under SCS [School of Chemical Sciences]
Research was conducted under DST grant and CSIR fellowship
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Hsu, Ya-Shu, and 許雅淑. "The study of pyrazolo[4,3-c]quinoline derivatives as inhibitor of p38α MAPK by computer molecular modeling." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/21523131607051410483.
Full textAbstract:
碩士高雄醫學大學
醫藥暨應用化學研究所碩士在職專班
97
This study analyses and modifies the model of Accerlys Discovery Studio with the pyrazolo[4,3-c]quinoline derivatives as inhibitor of p38α MAPK by computer molecular modeling. From this study we intend to find novel molecule to be potential anti-infection P38 MAPK inhibitors. The results of this study led to the discovery of 13 possible compounds which we have further predict their activities and the pharmacophore. Although preious studies suggested three amino acids involved in the interaction of typical p38α MAPK inhibitors, we have found the forth amino acid which was also involved. Through chemical binding of the forth amino acid, the inhibitory activity was further promoted.
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JHANG, JIA-WEI, and 張家瑋. "Part 1: Design and Attempted Synthesis of Acridone Derivatives as Potential ABC Transporters Inhibitors,Part 2: Design and Synthesis of Pyrazole Derivatives as System xc- Inhibitors." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/qg9258.
Full textAbstract:
碩士東海大學
化學系
105
Part 1: ABC(ATP-binding cassette) transporter proteins are responsible for the cellular efflux of metabolites or toxic substances to protect cells. Overexpression of ABC transporter protein occur when tumor cells are stimulated continuously by chemotherapeutic drugs,that to causing lack of drug accumulation drugs which lead to development of multidrug resistance (MDR). The development of MDR is a major obstacle to successful chemotherapeutic treatment of cancer patients. Acridones are naturally occurring alkaloids and one of its derivatives, Elacridar was shown to inhibit both ABC transporter proteins ABCB1 and ABCG2. In this study,acridone was used as lead compound to design and synthesize acridone derivatives. These derivatives were planned to be synthesized by coupling 4-acridinecarboxylic acid with respective amines. We have,however,only managed to prepare the acid chlorides and the activated acids. Nucleophilic attack by amine did not occur presumably due to the steric hindrance between the phenyl ring on the amine and acridone moiety. Part 2: System xc- mediates the exchange of extracellular L-cystine and intracellular L-glutamate across the cellular plasma membrane in a 1:1 manner. After the exchange, the intracellular L-cystine is rapidly reduced to L-CysH which is enzymatically incorporated into Glutathione(GSH) that can protect cell or tumors. when the efflux of L-Glu through system xc- becomes excessive, its function within the CNS turns from an excitatory transmitter to excitotoxin. Excitoxine caurse are cell poisoning/death which also vacating room for tumor expansion. In this study,we take pharmacophore model of isoxazole analogues by Patel et al as reference to design and synthesize sixteen pyrazole derivatives as system xc- inhibitors. 2,3-disubstituted derivatives were synthesized by witting reaction of hydrazine and dialkyl ethylenedicarboxylates. 1,3-disubstituted derivatives were synthesized by copper-catalyzed reaction of hydrazones and dialkyl ethylenedicarboxy-lates. At drug concentration of 50 μM,BBXc23 showed low cytotoxicity for glioblastoma cell,and BBXc23 also exhibited good inhibition for both L-glu efflux and cysteine uptake, which indicated that this compound may be a good system xc- inhibition.
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Lee, Cheng-Tien, and 李承典. "Studies on Synthesis and Light-Emitting Properties of ConjugatedPoly(p-phenylenevinylene) Derivatives Containing Pyrazole and 1,3,4-Oxadiazole Rings." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/67855487208244512188.
Full textAbstract:
碩士國立成功大學
化學系碩博士班
94
Six poly(p-phenylenevinylene) derivatives, P1~P2 with oxadiazole along the main chain and P3~P6 bearing two 1,3,4-oxadiazole rings and pyrazole rings from sydnone along the main chain were synthesized via Heck coupling. The new polymer are studied on their structure,physical and photoelectronic properties. The polymers dissolved readily in common organic solvents and had high glass-transition temperature values of 149°C ~ 167 °C for P3 ~P6.They were stable up to approximately 260°C ~ 350°C in N2 and the anaerobic char yield was around 28 ~ 35% at 800 °C except P1. UV-Vis spectra show three peaks at 374 ~ 410 nm ,296~344 nm and 240 nm that correspond to the π-π* transition of the conjugated polymer backbone, oxadiazole and aromatic, respectively. They emitted greenish- blue or yellow light in solution and emitted green or orange light with PL emission maxima at 485 ~ 573 nm. The energy gap and electron affinity of the polymers were estimated as 2.32~2.54 eV and 2.44~2.81eV, respectively. Electrochemical behavior of the polymers demonstrates that introducing the high electron affinity oxadiazole moiety and pyrazole into the backbone lowers both the HOMO and LUMO energy levels of the polymers, thus mitigating the problem of charge injection imbalance in polymer LEDs.
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Chang, En-Chiuan, and 張恩銓. "Synthesis of the Pyrazole Derivatives Containing Carbazole and 1,3,4-Oxadiazole Rings and Applied to Organic Electro-Luminescence Devices." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/60169640570777845151.
Full textAbstract:
碩士國立成功大學
化學系碩博士班
95
In this study, I had synthesized a series of pyrazole derivatives, and applied in organic electro-luminescence devices. The series of pyrazole derivatives were all synthesized from sydnone via 1,3-dipolar cycloaddition. Organic light-emitting diode (OLED) is a novel technology. The large size display can be made via this technology. Because of some organic materials have high fluorescence efficiency and semiconducting properties, they often applicable to electro-luminescence (EL) devices. The other hand, the emission colors can be determine via modify organic compounds. Hence, the organic material plays a decisive role in OLED technology. Compounds derived from 1,3,4-oxadiazoles had been reported having good electron-transporting properties and the pyrazole moiety is an electron-rich heterocycle. So we introduced 1,3,4-oxadiazoles into pyrazole derivatives. In order to improve thermostabilities and electro-luminescence properties, we introduced carcazole and phenyl into 1,3,4-oxadiazole-based pyrazole derivatives. The physical 、 chemical and electro-luminescence properties were studied by DSC 、 UV-Vis 、 CV and PL spectra. The OLED device was constructed by vapor deposition of the materials under vacuum onto the ITO-coated glass substrate. The I-V curves and EL spectra had proven that our new synthetic compounds were new efficient blue electroluminescent materials.
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Goswami, Arijit. "Studies on Coordination Complexes Metal Organic Framework (MOFs) and Network using Salicylic Acid Derivatives and Pyrazole based Ligand." Thesis, 2019. http://hdl.handle.net/10821/8222.
Full textAbstract:
The whole work is divided in three parts. The 1st part deals with synthesis if series of metal organic framework from bis-pyrazole ligands and various aromatic carboxylic acids and their potential application. the 2nd part contains synthesis and investigation of energy parametres of supramolecular framework resulting from the combination between a bispyrazole ligand and inorganic anions. The 3rd part and the final part contains synthesis of diverse metal organic framework and metal complexes based on chloro-salicyclic acid.Research was carried out under the supervision of Dr. Raju Mondal of the Inorganic Chemistry division under SCS [School of Chemical Sciences]
Research was conducted under DST grant and CSIR fellowship
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Tsai, Pi-Chen, and 蔡弼丞. "Synthesis and Solvatochromic Properties of Some Novel Symmetrical and Asymmetrical Heterocyclic Disazo Dyes Based on Pyrazolo[1,5-a]Pyrimidine Derivatives." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/49g7pn.
Full textAbstract:
博士國立臺灣科技大學
高分子系
95
The disertation consists of two main themes: Firstiy, (1) 3,5-Di-(amino or methyl)-4-substituted-azoly-pyrazole and 3-amino-5- methyl-4-substituted-azoly-pyrazole have been synthesized via the cyclization from hydrazine hydrate with 2-substituted-azoly-malono- nitrile, 3-sub-stituted-azoly-pentane-2,4-dione and 3-imino-2-substitu- ted-azoly-butyronitrile, respectively; and (2) 5-amino-3-methyl-4-substi -tuted-azoly-pyrazole and 3-amino-4-substituted-azoly-5-pyrazolone were prepared by coupling reaction of aniline derivatives with 3-amino-5-pyrazolone and 5-amino-3-methylpyrazole, respectively. The effect of maximum absorption spectra on synthesized pyrazole monoazo dyes with different substituents and their different locations was also evaluated by UV-ray in acetone. After a series of analyses, we can realize that the substituent effect of maximum absorption spectra on the 5th position of pyrazole ring is more dominant than the 3rd position of that. Secondly, (1) 3,6-Diphenylazo pyrazole[1,5-a]pyrimidine disazo dyes were synthesized both by the cyclization of 2-(4-substituted- phenylazo)- malononitrile with 3,5-diamino-4-(4-substituted-phenyl- azo)-pyrazole; (2) 4-(Aryl or hetaryl)azo-3,5-diaminopyrazole com- pounds with arylazo- and hetarylazo- malononitriles were prepared by the cyclization to obtain the 3,6-di-(aryl or hetaryl)- azo-2,5,7-triamino- pyrazolo[1,5-a]pyrimidine heterocyclic disazo dyes; (3) 3,6-dihetaryl- azo-2,5,7-triamino-pyrazolo[1,5-a]pyrimidine heterocyclic disazo dyes have been synthesized via the cyclization from some substituted hetarylazomalononitrile precursors with various substituted hetarylazo- pyrazole compounds. The effect of maximum absorption spectra on these prepared hetercyclic disazo dyes with and various solvents was investigated by the UV-ray test. In addition, the effect due to different substituents and polarities was also evaluated.The solvatochromic behavior of these dyes in various solvents with different dielectric constants reveals bathochromic shifts as the solvent polarity is increased. Although, the substituents can be arylazo or hetarylazo by comparing with the synthesized hetarcyclic disazo dye, we can know the different effect of maximum absorption spectrum for pyrazole- [1,5-a]pyrimidind compounds. By the related analyses, the maximum absorption spectrum of dyes may have a trend of moving to long wavelength when the substituted on the 3,6th position of pyrazole- [1,5-a]pyrimidind ring changing to hetarylazo group. All synthesized compounds in this disertation were analyzed to recognize their chemical structures through spectrum identification of FT-IR, UV, and 1H-NMR and EA.
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Wu, Hong-Jhou, and 吳宏洲. "Synthesis of Pyrazolo[1,5-a]pyridine Derivatives via Hydrazine and 4-ene-2,6-diyne-one by Copper(I) chloride-catalyzed." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/38283112889469025155.
Full textAbstract:
碩士高雄醫學大學
醫藥暨應用化學研究所碩士班
95
Recently, we developed synthetic methods to a series of aromatic compounds such as isoquinolones, phenanthridinones, and biphenyls via anionic cycloaromatization of enediynes. We found that treatment of (Z)-1-phenyltrideca-4-en-2,6-diyn-1-one (78b) with 5 eq hydrazine and 4 eq copper(I) chloride in refluxing CH3CN afforded pyrazolo[1,5-a]pyridine (81) in 85 % yield.
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Su, Wei-Nien, and 蘇威年. "Convenient and Efficient“One-pot”Synthesis of N-(1,3-Diphenyl-1H-pyrazole-5-yl)amide Derivatives: Positive allosteric Modulators of mGluR5." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/14099096043064355484.
Full textAbstract:
碩士中國醫藥大學
藥物化學研究所
96
Glutamate is the major excitatory transmitter in the mammalian central nervous system. Metabotropic glutamate receptors (mGluRs) play an important role in controlling neuronal excitability and synaptic transmission in the central nervous system (CNS) of the mammalian brain. N-(1.3-Diphenylare1-H-pyrazol-5-yl)benzamide derivatives were recently developed as the first centrally active positive allosteric modulator of rat and human metabotropic glutamate receptor mGluR5 subtype. N-(1,3- diphenyl-1H-pyrazol-5-yl)amide derivatives were convenient and efficient synthesized by using phenylhydrazine, benzoylacetonitrile, and a series of acylation agents. Two steps of condensation-cyclization and acylation were performed in one-pot to give the corresponding N-(1,3-diphenyl-1H-pyrazol-5-yl)amide analogues in good to excellent yields (70–90%).
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陳孟榆. "Pyrazole Calix[4]arenes as Highly Selective Fluorogenic Sensors for Silver (I) and Mercury (II) and Synthesis of Pillar[5]arene Derivatives." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/04499796060226609005.
Full textAbstract:
碩士國立交通大學
應用化學系碩博士班
99
This study is divided into two parts. First, two series of lower-rim modified calix[4]arene with pyrazole substituents were synthesized. Using phenyl pyrazole calix[4]arenes as basic synthesis frameworks, we synthesized phenylanthryl pyrazole calix[4]arenes 76 and 77 and control compounds 78 and 79 as fluorogenic ions sensors. Based on the results from UV-Vis, fluorescence and 1H-NMR spectrometry, we found that pyrazole calix[4]arenes 77 and 79 recognized Ag+ and Hg2+ with excellent selectivity in MeOH/CHCl3 (v/v = 4:1), respectively. Compound 77 induced 141% enhancement of fluorescence intensity toward Ag+, and compound 79 showed 51% fluorescence quenching effect toward Hg2+.Furthermore, the complexation of compound 77 with Ag+ and 79 with Hg2+ both showed 1:1 host-guest stoichiometry based on by Job plot obtained from fluorescence and 1H-NMR titration spectra. We also found the binding constants of 77 with Ag+ was (1.12 ± 0.17) × 104 M-1 and 79 with Hg2+ was (1.33 ± 0.20) × 104 M-1.Second, the research was focused on the reaction condition to synthesize pillar[5]arenes. Pillar[5]arenes 38 and 83 were successfully and facile synthesized by cyclization reaction with high yield. These compounds were obtained via borontrifloride etherate catalyzed procedure with 1,4-dialkoxyphenyl monomer and paraformaldehyde under 0.1 M solution. Besides, a synthetic route to difunctional pillar[5]arene 95 was also developed by combining two different monomers with 4:1 ratio using the conditions stated above.
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Chou, Li-Chen, and 周立琛. "Synthesis and anticancer activity of 1,3,5-substituted selenolo[3,2-c]pyrazole analogues、Synthesis and anticancer activity of hydrophilic phosphate prodrugs of 2-phenyl-4-quinolone derivatives." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/72588313584030324230.
Full textAbstract:
博士中國醫藥大學
藥物化學研究所博士班
97
The purpose of this study is to develop compounds with potential anticancer activity as new drug candidate. This thesis consists of two parts. In the first part, four different skeletons of YC-1 derivatives [furopyrazole derivatives (11-22, 28-36), thienopyrazole derivatives (42-45, 50-53), selenopyrazole derivatives (67-72, 75-77), and indazole derivatives (99−118, 123−128)] were synthesized in order to expand the substance patent’s inclusion of YC-1 and find new candidate with better anticancer activity than YC-1, and constructed their SAR in NCI-H226 and A498 cells. Compound 13 (CLC107), 44 (CLC015), 69 (CLC005), and 127 (CLC802a) were chosen for evaluation against 60 human cancer cell lines (the NCI-60) and COMPARE program analysis, and indicated that four compounds were with great development value since they possessed novel mechanism of action different from existing anticancer drugs. Finally compound 127 was proved to demonstrate anticancer activity similar to YC-1 in animal model, it is thus a new candidate of YC-1 in drug development. In the second part, the problem of 2-phenyl-4-quinolone derivatives in pharmacokinetics is resolved. In order to improve solubility problem, a phosphoric acid was attempted to be attached to 4-ketone of 2-phenyl-4-quinolone, and thus phosphate monosodium salts of 2-phenyl-4-quinolone derivatives were successfully created, which were expected to be applied by po and iv routes in clinics. Among 2-phenyl-4-quinolone derivatives, we focus on compound 8 which demonstrated the most significant antitumor activity. According to the data of Pharmacokinetics, compound 35 was proved to be transformed in vivo to compound 8 (CHM-1). After the assessment of safety pharmacology of compound 35 in enzyme activity assay and receptor binding assay, we predict it is very effective and safe drug while there should not be too many side effects in clinical trials. Besides, it showed excellent antitumor activity in SKOV-3 Xenograft SCID mice model and CT-26 colon adenocarcinoma Balb/c mice orthotopic model. It is confirmed that compound 35 (CHM-1-P-Na) is a drug candidate for further development as a potential anticancer agent in the clinic. We hope this series of compounds can successfully become clinical therapeutic agents which are beneficial to human beings.
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Cardoso, Inês Sofia Soares Gomes Lains. "Design and synthesis of a novel pyrazolopyrimidine compound as a potential kinase inhibitor." Master's thesis, 2016. http://hdl.handle.net/10451/34606.
Full textAbstract:
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2016Cancer is a generic term for a group of diseases in which abnormal cells have a fast and uncontrolled growth and proliferation, invading neighbouring tissues and spreading to parts of the body different from where it started. Cancer is placed second at the most important causes of death and morbidity in Europe and accounts for 1 in every 7 deaths worldwide, which is more than HIV, tuberculosis and malaria combined. Furthermore, the number of new cases worldwide is expected to rise by about 70% over the next 20 years due to the growth and aging of the population. Nowadays, there are several options of treatment available for different types of cancer. However, current treatment modalities remain inadequate and in need of improvement regarding selectivity, potency and toxicity. For this reason, both academia and pharmaceutical industry have shown interest in deeply investigating carcinogenesis at a molecular level, improving existing drugs and discovering new compounds for cancer treatment. Given the role of proteins kinases and phosphorylation processes in carcinogenesis by driving many of the hallmark phenotypes of cancer biology, kinases are privileged targets of new antineoplasic therapies and pharmacological tools have been developed to inhibit protein phosphorylation. Recently, several kinase inhibitors have been studied and approved for the treatment of some types of cancer, such as Imatinib, Sorafenib, among others. Among kinases inhibitors, pyrazolopyrimidines-derived compounds have been investigated and are used as treatment for several diseases, acting like antineoplasic, antivirals, and tuberculostatic agents, among others. Different kinase inhibitors with pyrazolopyrimidines as central core structure were studied and produced. The aim of this thesis was to synthesize a pyrazolo[3,4-d]pyrimidine derivative chemically designed as a hybrid of two previously synthesized compounds containing the mentioned central core structure and which had good and complementary results on the IC50 test against subfamilies of kinases, suggesting an improvement in selectivity and efficacy. One part of each of the previously studied molecules were synthesized separately and attached to each other through a Suzuki-Miyaura cross-coupling reaction.
Cancro é um termo genérico que engloba um grupo de doenças nas quais células anormais crescem e proliferam rápida e descontroladamente, invadindo tecidos circundandes e outras partes do corpo distantes do local de origem. O cancro é a segunda causa de morte e morbilidade na Europa e é responsável por 1 em cada 7 mortes a nível mundial, representando mais do que HIV, tuberculose e malária no seu conjunto. Além disso, o número de novos casos, numa perspectiva mundial, é esperado que cresça em, aproximadamente, 70% nos próximos 20 anos, devido ao crescimento e envelhecimento da população. Actualmente, estão disponíveis várias opções de tratamento para diferentes tipos de cancro. No entanto, as modalidades actuais de tratamento permancem inadequadas e por melhorar, em relação à selectividade, potência e toxicidade. Por esta razão, a academia e a indústria farmacêutica têm demonstrado interesse em investigar a carcinogénese a um nível molecular, de forma a aperfeiçoar fármacos já existentes e a descobrir novos compostos para o tratamento do cancro. Considerando o papel das proteínas cinases e dos processos de fosforilação na carcinogénese, por conduzir muitos dos fenótipos característicos da biologia do cancro, as cinases representam um alvo priveligiado de novas terapias antineoplásicas e têm sido desenvolvidas ferramentais farmacológicas para inibir a fosforilação proteica. Recentemente, vários inibidores de cinases têm sido estudados e aprovados para o tratamento de alguns tipos de cancro, como por exemplo Imatinib, Sorafenib, entre outros. De entre os inibidores de cinases, os compostos derivados de pirazolo-pirimidinas têm sido investigados e são utilizados como tratamento para diversas doenças, actuando como antineoplásicos, antivirais e agentes tuberculoestáticos, entre outros. Foram estudados diferentes inibidores de cinases com o núcleo estrutural constituído por pirazolo-pirimidinas. O objectivo da presente tese consistiu na síntese de um derivado de pirazolo[3,4-d]pirimidina, quimicamente desenhado como um híbrido de dois compostos previamente sintetizados que contêm o mencionado núcleo estrutural e que apresentaram bons resultados, porém complementares, no teste de IC50 contra subfamílias de cinases, sugerindo a necessidade de melhoria quanto à selectividade e eficácia. Uma parte de cada uma das moléculas previamente estudadas foram sintetizadas separadamente e ligadas através de uma reacção de acoplamento de Suzuki-Miyaura.
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Chang, Chun-Hsi, and 張濬璽. "The study of selective synthesis and biological activity of pyrazolo[3,4-d]pyrimidine, N-(1H-pyrazol-5-yl)formamide, or N-(1H-pyrazol-5-yl)formamidine derivatives from N-1-Substituted-5-aminopyrazoles with new Vilsmeier-type reagents." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/95634777776867134802.
Full textAbstract:
碩士中國醫藥大學
藥物化學研究所碩士班
102
Various halomethyleniminium salts as novel Vilsmeier reagents were synthesized from the reaction of formamide or N-methylformamide with phosphoryl chloride. Treatment of N-1-substituted-aminopyrazoles including, N-1-(2-pyridinyl)-5-aminopyrazoles and N-1-(2-quinolinyl)-5-aminopyrazoles with these Vilsmeier reagents to obtain the corresponding pyrazolo[3,4-d]pyrimidine, N-(1H-pyrazol-5-yl)formamide, or N-(1H-pyrazol-5-yl)formamidine products. The experimentant results were different with our previous data which the formylated amidylpyazole and formamidine products were obtained under the similar reaction conditions.