Novel heterocyclic nitrofurfural hydrazones. In vivo antitrypanosomal activity

Novinsion, T; Bhooshan, B.; Okabe, Tadashi; Gr, Revankar; Rk, Robins; Senga, Keitaro; Hr, Wilson

doi:10.1021/jm00226a013

Cited by 59 publications

(38 citation statements)

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“…Em geral, os nitrofuranos apresentam atividade antibacteriana, que se deve à redução enzimática do grupo nitro in vivo, produzindo espécies tóxicas que, subseqüentemente, causam danos ao DNA das bactérias 10 . O grupo nitro está presente ainda em várias substâncias usadas como antitumorais, tripanocidas, fungicidas, antivirais e antiparasitários 10,11 . Hidrazonas, em geral, possuem diversas atividades biológicas, como anti-inflamatória, antitrombótica e analgésica 12,13 .…”

Section: Introductionunclassified

Síntese e caracterização de novos complexos de platina (II) com ligantes derivados do furano e nitrofurano

Guerra¹,

Fontes²,

Almeida³

et al. 2005

Quím. Nova

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Recebido em 15/7/04; aceito em 24/2/05; publicado na web em 30/6/05 SYNTHESIS AND CHARACTERIZATION OF NEW PLATINUM (II) COMPLEXES CONTAINING FURAN AND NITROFURAN DERIVED LIGANDS. Platinum (II) complexes, for example, cisplatin and carboplatin, have been used as chemotherapeutic agents for the treatment of various types of cancer. Several other complexes of this metallic ion are also under clinical evaluation. This work describes the synthesis of five new platinum (II) complexes having furan and 5-nitrofuran derivatives and chloride as ligands. The compounds were characterized by NMR, IR and elemental analysis.Keywords: platinum (II) complexes; furan; nitrofuran. INTRODUÇÃOA quimioterapia do câncer utiliza-se tanto de compostos orgâ-nicos (como por ex., taxol) quanto de compostos inorgânicos (por ex., cisplatina e carboplatina, Figura 1), que podem ser administrados sozinhos ou em associação com outras drogas.Há algumas décadas, a cisplatina, cis-diaminodicloroplatina(II), vem sendo usada no tratamento de vários tipos de neoplasias, como de pulmão, cabeça, esôfago, estômago, linfomas, melanoma, osteossarcoma, de mama e cérvix 1 . Por ex., em combinação com bleomicina e vimblastina, a cisplatina promove a cura em 80% dos casos de câncer testicular e, em combinação com paclitaxel, prolonga o tempo de vida de pacientes com câncer ovariano em está-gio avançado 2 . A utilização da cisplatina, entretanto, apresenta alguns pontos negativos, como aparecimento de resistência celular, pouca solubilidade em água e efeitos colaterais graves, como nefrotoxicidade, neurotoxicidade, ototoxicidade e toxicidade gastrointestinal 3,4 . Acredita-se que muitos dos efeitos adversos observados, principalmente nefrotoxicidade, estejam relacionados com a ocorrên-cia de ligação do complexo de platina com proteínas e peptídeos, como a glutationa, e a conseqüente acumulação destes adutos no organismo 5 . Sabe-se também que o mecanismo de ação de compostos de platina, em geral, envolve a interação destes com o DNA, configurando-se uma lesão em nível molecular 6,7 . A preparação de novos complexos de platina tem sido direcionada para o desenvolvimento de compostos mais eficazes e menos tóxicos. Desta maneira, cerca de 3000 complexos já foram sintetizados e testados, mas somente três outros são usados hoje: a carboplatina, a oxaloplatina e a nedaplatina 2 . As pesquisas nesta área continuam, não só no sentido de se obter um análogo que apresente menos efeitos colaterais, mas que também exiba um espectro de atividade maior, principalmente no que diz respeito às células resistentes à cisplatina.Neste trabalho discute-se a síntese e caracterização de novos complexos de platina(II) com ligantes derivados do furano e do 5-nitrofurano que representam diferentes classes de compostos quí-micos, como hidrazonas, hidrazidas, oximas, semicarbazonas e aminas. Nosso grupo de pesquisa publicou recentemente trabalho envolvendo a preparação de complexos de cobre (II) com dois destes derivados 8 . Estes ligantes apresentam atividade biológica ou pertencem à um...

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Section: Introductionunclassified

Síntese e caracterização de novos complexos de platina (II) com ligantes derivados do furano e nitrofurano

Guerra¹,

Fontes²,

Almeida³

et al. 2005

Quím. Nova

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“…Pyrazolopyrimidines have multiple pharmacological activities including anti-inflammatory [1], antitumor [2], antibacterial [3], anti-viral [4], antimetabolites [5], anxiolytic [6], antitrypanosomal [7], antichistosomal [8], and analgesic [9]. They are known to act as CRF 1 antagonist [10].…”

Section: Introductionmentioning

confidence: 99%

“…Synthesis of 3,6-diarylpyrazolo[1,5-a]pyrimidin-7-amine(7) was subjected to formylation reaction with DMF-DMA. Interestingly, formylated amine 8 was obtained in good yield and short reaction time, the structure of which was well established with the help of 1 H NMR,13 C NMR and Mass Spectrometry.…”

mentioning

confidence: 99%

A facile environment-friendly one-pot two-step regioselective synthetic strategy for 3,7-diarylpyrazolo[1,5-a]pyrimidines related to zaleplon and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines assisted by KHSO $$_{4}$$ 4 in aqueous media

2015

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3-Aminopyrazoles required for the synthesis of pyrazolo[1,5-a]pyrimidines were obtained by the reaction of enaminonitriles with hydrazine hydrate. The resulting aminopyrazoles are reacted with formylated acetophenones under reflux at [Formula: see text] assisted by KHSO[Formula: see text] in aqueous media to form regioselectively 3,7-diarylpyrazolo[1,5-a]pyrimidines and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines. X-ray crystallography of selected compounds 5b and 7i further confirmed the regioselective formation of these products.

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“…Pyrazolo [1,5-a] pyrimidines are purine analogues and as such have useful properties as antimetabolites in purine biochemical reactions. Compounds of this class have attracted wide pharmaceutical interest because their antitrypanisommal activity, 3 antischistosomal activity, 4 activity as HMG-CoA reductase inhibitors, 5 COX-2 selective inhibitors, 6 AMP phosphodiesterase inhibtors, 7 KDR kinase inhibitors, 8 selective peripheral benzodiazepine receptor ligants 9 and as antianxiety agents. 10 Recently other pharmaceutical activity has been reported, for example, as an agent for the treatment of sleep disorders 11 and as an oncological agent.…”

Section: Introductionmentioning

confidence: 99%

2-methyl-7-substituted pyrazolo[1,5-a]pyrimidines: highly regioselective synthesis and bromination

Martins¹,

Scapin²,

Frizzo³

et al. 2009

J. Braz. Chem. Soc.

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Este trabalho descreve a reação de ciclocondensação de 3-amino-5-metil-1H-pirazol com 1,1,1-tricloro-4-alcóxi-3-alquen-2-onas [CCl 3 C(O)CH=C(R 1 )OR, onde R 1 /R = H/Me, Me/Et, Et/Me, Pr/Et, Bu/Me, iso-Bu/Me] e β-dimetilaminovinil cetonas [R 2 C(O)CH=CHNMe 2 , onde R 2 = Ph, Ph-4-Me, Ph-4-F, Ph-4-Cl, Ph-4-Br, Ph-4-NO 2 , fur-2-il, tien-2-il, pirrol-2-il, pyrid-2-il], em refluxo de ácido acético para a obtenção de uma série de catorze pirazolo [1,5-a]pirimidinas. Os produtos foram obtidos em bons rendimentos (65-98%). Este trabalho apresenta ainda uma metodologia simples e seletiva para a obtenção de 3-bromo-pirazolo [1,5-a] IntroductionAmong the broad range of templates, heterocycle scaffolds represent the most promising molecules as lead structures in the discovery of novel synthetic drugs 1 and the revision of synthetic methods for their obtainment are intense.2 In particular, the pyrazolo[1,5-a]pyrimidine heterocyclic can be found in a large number of pharmaceutical agents with a diverse range of activities. Pyrazolo [1,5-a] 13 However, a facile procedure that can incorporate diversity structural it is high desirable. There are a limitedness number and variety of pyrazolo pyrimidines trifluoromethyl substituted described in literature.14 Conversely, pyrazolo[1,5-a] pyrimidines trichloromethyl substituted are rare. 15 The most convenient method to construct trihalogenated compounds is to use halogen-containing building blocks as starting reagents. 16,17 Our research group developed a general procedure for preparing β-alkoxyvinyl trihalomethyl ketones by acylation of enol ethers and acetals using 2-Methyl-7-Substituted Pyrazolo[1,5-a]pyrimidines J. Braz. Chem. Soc. 206 functionalized acyl groups CX 3 CO (where X = F and Cl). 16In addition, we have exhaustively studied the versatility of the β-alkoxyvinyl trihalomethyl ketones on heterocyclic synthesis and our research have resulting in outstanding contributions to heterocyclic synthesis. 2,16 On the other hand, aminopyrazoles are known to be highly reactive heterocyclic compounds, e.g., the nucleophilic attack of C-4 of the aminopyrazoles on the carbonyl groups, 18 and the N-nucleophilic attack on aromatic aldehydes yielding aldimines, have been extensively reported.19 Aminopyrazoles also react as electron-rich dienophiles in the inverse electron demand Diels-Alder [4+2] cycloaddition reactions. 20The use of 3-and 5-aminopyrazoles as precursors of fused heterocycles, such as pyrazolo[1,5-a]pyrimidines 21 and pyrazolo [3,4-b]pyridines 22 has also been described. Additionally, halogenation of pyrazolo[1,5-a]pyrimidines can be used to obtain key substructures in a large variety of compounds with important biological activities, and the halogenated compounds also can be used as reagents in cross-coupling reactions with terminal acetylenes, organotin aryl derivatives or aryl boronic acids. 23 Thus, in the course of our investigations on heterocyclic chemistry and in view of the growing importance of halogenated heterocycles, the aim of this study is to show...

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Novel heterocyclic nitrofurfural hydrazones. In vivo antitrypanosomal activity

Cited by 59 publications

References 1 publication

Síntese e caracterização de novos complexos de platina (II) com ligantes derivados do furano e nitrofurano

Síntese e caracterização de novos complexos de platina (II) com ligantes derivados do furano e nitrofurano

A facile environment-friendly one-pot two-step regioselective synthetic strategy for 3,7-diarylpyrazolo[1,5-a]pyrimidines related to zaleplon and 3,6-diarylpyrazolo[1,5-a]pyrimidine-7-amines assisted by KHSO $$_{4}$$ 4 in aqueous media

2-methyl-7-substituted pyrazolo[1,5-a]pyrimidines: highly regioselective synthesis and bromination

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