ChemInform Abstract: PROSTAGLANDIN ANALOGS. PART 2. SYNTHESIS OF NEW DERIVATIVES FROM SAFROLE ISOLATED FROM SASSAFRAS OIL

Barreiro, Eliezer J.; Costa, Paulo R.R.; Coelho, Fernando; Farias, Florence M. C. de

doi:10.1002/chin.198544327

Cited by 5 publications

(5 citation statements)

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“…88 A series of homologous of the  and  side-chains of TXA 2 was likewise prepared to furnish different analogues of compound 86, including derivative 87. 8,89 The conformational restriction approach was likewise employed on the structure of prostaglandin analogue 84, in order to design compound 88 that was synthesized in 8 linear steps from safrole (Figure 34). The papers published by Pereira and coworkers (1989) 91 and Barreiro and Lima (1992) 92 In similar manner, others me-too analogues of anti-inflammatory drugs were synthesized from safrole (1) (Figure 36).…”

Section: Lassbio's Ontri Utionmentioning

confidence: 99%

Safrole and the Versatility of a Natural Biophore

Lima

2015

Revista Virtual De Química

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Safrol e a Versatilidade de um Biofóro NaturalResumo: Safrol (1) obtido de óleos essenciais de diferentes espécies vegetais tem ampla aplicação na indústria química como precursor sintético do butóxido de piperonila, piperonal e de fármacos como a tadalafila, cinoxacina e levodopa. Do ponto vista toxicológico, é considerado uma hepatotoxina por mecanismo de bioativação metabólica conduzindo a formação de intermediários eletrofílicos, e tem sido descrito como inibidor de diferentes isoenzimas da família CYP450. A versatilidade de sua estrutura, permitindo várias transformações químicas, e a natureza biofórica de sua unidade benzodioxola ou metilenodioxifenila conferem-lhe características singulares, que o tornam atrativo material de partida para a síntese de compostos com distintas atividades farmacológicas. Exemplos selecionados de compostos bioativos, naturais e sintéticos, contendo o sistema benzodioxola serão comentados, incluindo aqueles provenientes de contribuição específica do LASSBio®.

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Section: Lassbio's Ontri Utionmentioning

confidence: 99%

Safrole and the Versatility of a Natural Biophore

Lima

2015

Revista Virtual De Química

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“…Synthesis of methyl-3,4-methylenedioxybenzoate (3), 3,4-methylenedioxybenzoylhydrazine (4), (E)-N′-(thiophen-3-ylmethylene)benzo[d] [1,3] dioxole-5-carbo-hydrazide (5) Piperonal 2 was synthesized from natural safrole 1 [13,14]. The compounds 3, 4, and 5 were synthesized as previously described by our group [11,15] Synthesis of (E)-N-methyl-N′-(thiophen-3ylmethylene)benzo[d] [1,3]dioxole-5carbohydrazide (LASSBio-1289) The N-acylhydrazone 5 (1.0 mmol) and potassium carbonate (3.0 mmol) were suspended in 5 mL of acetone.…”

Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca²⁺ channels

Pereira

Kümmerle

Fraga

et al. 2012

Fundamemntal Clinical Pharma

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New bioactive N-acylhydrazone derivatives synthesized from safrole previously have been found to promote intense vasodilation and antihypertensive activity. In this study, we describe the synthesis and the cardiovascular effects of the new N-acylhydrazone derivative (E)-N-methyl-N'-(thiophen-3-ylmethylene)benzo[d][1,3]dioxole-5-carbohydrazide (LASSBio-1289). Thoracic aorta and left papillary muscles from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were prepared for isometric tension recording. LASSBio-1289 promoted relaxation of endothelium-intact and denuded aortic rings with respective pIC₅₀ (-log IC₅₀) values of 5.07 ± 0.09 and 4.26 ± 0.09 (P < 0.001) for WKY rats and 5.43 ± 0.05 and 5.58 ± 0.07 (P > 0.05) for SHR. The vasodilator activity of LASSBio-1289 was increased in the KCl-contracted aorta. LASSBio-1289 attenuated the contracture elicited by Ca(2+) in depolarized aorta from both WKY rats and SHR. In endothelium-intact aorta from WKY rats, LASSBio-1289-induced relaxation was unchanged after incubation with propranolol, ZM 241385, atropine, diphenhydramine, and HOE140, but was significantly reduced by L-NAME and ODQ. LASSBio-1289 decreased papillary muscles contractility only at concentrations above 200 μm. Acute intravenous injection of LASSBio-1289 (3 mg/kg) produced a significant hypotensive response in SHR but not in WKY rats, suggesting its antihypertensive profile. The antihypertensive effect was also observed in SHR during 14 days of intraperitoneal and oral administration. In conclusion, our data demonstrated that LASSBio-1289 induces both endothelium-independent vasorelaxation involving the inhibition of Ca(2+) influx through L-type Ca(2+) channels in aorta from WKY rats and SHR, and endothelium-dependent relaxation mediated by the NO/cyclic GMP pathway in WKY rats.

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“…In this paper we describe the synthesis and pharmacological profile of these new isochromanylacetylaryl hydrazone derivatives (3), using safrole (4), an abundant natural Brazilian product available from Sassafras oil (Ocotea pretiosa Mer., Lauraceae), as the synthetic starting material 19 .…”

Section: Introductionmentioning

confidence: 99%

The synthesis of new isochromanylacetylarylhydrazones designed as probable non-addictive analgesic agents

Santos¹,

Barreiro²,

Braz‐Filho³

et al. 1997

J. Braz. Chem. Soc.

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A síntese e o perfil anti-inflamatório e analgésico dos novos agentes isocromanilacetilarilidrazônicos são descritos neste artigo. A rota sintética utilizada neste trabalho explora como passo chave para a construção de um anel heterocíclico de seis membros, a ciclização catalisada por um ácido de Lewis, que representa uma modificação da reação de Friedel-Crafts. Estes novos derivados (3) são obtidos em ca. de 85% de rendimento, a partir do safrol (4) utilizado como produto natural abundante, isolado do óleo de Sassafrás. A análise dos espectros de RMN destes novos derivados indica a natureza diastereoisomérica a nível da ligação C=N, na razão de 70:30, onde a maior contribuição é relativa ao isômero (E). Os resultados obtidos da avaliação farmacológica de (3) no teste do edema de pata de rato induzido por carragenina e no teste de contorções abdominais induzidas pelo ácido acético, indicam a natureza farmacofórica da unidade acilidrazona para a atividade analgésica observada nesta série. O papel dos substituintes na sub-unidade arila na atividade farmacológica parece indicar que a presença de grupos hidrofóbicos podem elevar o perfil analgésico. Estes novos derivados isocromanilacetilarilidrazônicos (3) representam nova classe de agentes analgésicos não-convencionais.The synthesis and pharmacological profile as analgesic and anti-inflammatory agents of new isochromanylacetylarylhydrazone derivatives (3) are described in this paper. The synthetic route used in this work to construct the heterocyclic six member ring explored a Lewis acid-catalyzed cyclization process as the key step, which represents a modified Friedel-Crafts reaction. These new derivatives (3) were obtained in ca. 85 % overall yields from the starting material safrole (4), an abundant natural product isolated from Sassafras oil. The NMR spectral analysis of these new derivatives indicated, at the C=N double bond level, the diastereomeric nature in a 70:30 ratio, where the major compound is the (E)-isomer. The results obtained from the pharmacological evaluation of (3) using the carrageenan-induced rat paw edema test and the acetic acid solution-induced constrictions in mouse test, indicated the pharmacophoric nature of the acylarylhydrazone moiety to the analgesic activity observed in this series.The role of the aryl substituents in the bioactivity seems to indicate that the presence of hydrophobic groups may improve the analgesic profile. These new isochromanylacetylarylhydrazone derivatives (3) represent a new class of non-addictive analgesic agents.

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ChemInform Abstract: PROSTAGLANDIN ANALOGS. PART 2. SYNTHESIS OF NEW DERIVATIVES FROM SAFROLE ISOLATED FROM SASSAFRAS OIL

Cited by 5 publications

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Safrole and the Versatility of a Natural Biophore

Safrole and the Versatility of a Natural Biophore

Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca²⁺ channels

The synthesis of new isochromanylacetylarylhydrazones designed as probable non-addictive analgesic agents

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ChemInform Abstract: PROSTAGLANDIN ANALOGS. PART 2. SYNTHESIS OF NEW DERIVATIVES FROM SAFROLE ISOLATED FROM SASSAFRAS OIL

Cited by 5 publications

References 0 publications

Safrole and the Versatility of a Natural Biophore

Safrole and the Versatility of a Natural Biophore

Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca2+ channels

The synthesis of new isochromanylacetylarylhydrazones designed as probable non-addictive analgesic agents

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Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca²⁺ channels