Factorial design study to access the “green” iodocyclization reaction of 2-allylphenols

Corrêa, Michelle Fidelis; Barbosa, Álefe Jhonatas Ramos; Sato, Rie; Junqueira, Luis Otávio; Politi, Mário José; Rando, Daniela; Fernandes, João Paulo S.

doi:10.1515/gps-2015-0101

Cited by 6 publications

(11 citation statements)

References 8 publications

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“…The 2-allylphenol was used as a starting material ( Figure 2 ) for compounds 1a – d , which was converted into the (2-iodomethyl)-2,3-dihydrobenzofuran, as previously described by our group, giving excellent yield ( Table 1 and Supplementary Information) ( Corrêa et al, 2016 , 2017 ). The iodinated dihydrobenzofuran 4a was then reacted with the corresponding piperazines in considerable excess, giving moderate to good yields.…”

Section: Resultsmentioning

confidence: 99%

“…Both steps resulted in good to excellent yields ( Table 1 and Supplementary Information). With the 4-substituted 2-allylphenols, the final compounds were prepared in the same fashion to compounds 1a – d ( Corrêa et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…The intermediate compounds ( Figure 2 and Supplementary Figure S1 ) were synthesized according to previously reported procedures from our group ( Corrêa et al, 2016 , 2017 ). The experimental details can be found in the Supplementary Information.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors with Anti-inflammatory Potential

et al. 2017

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The histamine receptors (HRs) are traditional G protein-coupled receptors of extensive therapeutic interest. Recently, H3R and H4R subtypes have been targeted in drug discovery projects for inflammation, asthma, pain, cancer, Parkinson’s, and Alzheimer’s diseases, which includes searches for dual acting H3R/H4R ligands. In the present work, nine 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01 series) molecules were synthesized and evaluated as H3R and H4R ligands. Our data show that the N-allyl-substituted compound LINS01004 bears the highest affinity for H3R (pKi 6.40), while the chlorinated compound LINS01007 has moderate affinity for H4R (pKi 6.06). In addition, BRET assays to assess the functional activity of Gi1 coupling indicate that all compounds have no intrinsic activity and act as antagonists of these receptors. Drug-likeness assessment indicated these molecules are promising leads for further improvements. In vivo evaluation of compounds LINS01005 and LINS01007 in a mouse model of asthma showed a better anti-inflammatory activity of LINS01007 (3 g/kg) than the previously tested compound LINS01005. This is the first report with functional data of these compounds in HRs, and our results also show the potential of their applications as anti-inflammatory.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors with Anti-inflammatory Potential

et al. 2017

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ ortho-allylphenol followed by deiodination with basic alumina using a previously reported method 20,21 . Their structures were confirmed by analysis of NMR ( 1 H and 13 C) and HRESIMS data.…”

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confidence: 99%

Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A

Morais

Conserva

Varela

et al. 2020

Sci Rep

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Chagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi, endemic in Latin America and recently found in non-endemic countries of North America, Europe and Asia. The main form of transmission depends on the presence of a vector, being Triatoma infestans the most common 1. It is estimated that over eight million people are infected by the parasite and 70 million are at risk, living on endemic areas or in places where the control of other forms of transmission (oral, blood transfusion or organ transplant) is not rigid 2. CD is a two-stage disease: the acute phase, characterized by the high parasitaemia, and invasion by trypomastigote forms of different organs and the chronic phase, which may be latent for decades before appearance of clinical signs and usually associated with the development of cardiomyopathy 3,4. The available therapy for the treatment of CD is actually restricted to two approved drugs: benznidazole and nifurtimox, remains a controversial issue, with contradictory results in the chronic phase of the disease 5-8. Furthermore, these nitrocompounds showed several side effects associated to prolonged treatment regimens. Several clinical trials involving drug-repositioning (such as antifungal azoles) were carried out as well as studies involving new molecules, but none have reached the market yet 4. Therefore, new effective drugs for the treatment of CD are still needed. The Drugs for Neglected Diseases initiative (DNDi) defines that a desirable hit compound should present considerable efficacy (IC 50 < 10 µM), selectivity (>10-fold over mammalian cells) and adequate oral bioavailability 9. Natural products have always been a source of a great variety of bioactive molecules, mostly substances from the organism secondary metabolism. Many drugs available in the market are natural products as found in nature or compounds designed based on the structure and activity of these natural products (semi-synthetic or completely synthetic) 10. The biodiversity of plants makes them a commonly explored source of novel bioactive compounds, providing molecules with distinct structures, complex or simple, with huge chemical variety 11. Several research groups are focused on the isolation and identification of novel compounds with antimicrobial activity from plant extracts, aiming to use them as prototypes for drug discovery against Chagas disease 12. In this context, licarin A is a neolignan isolated from different plant species with reported activity against Mycobacterium tuberculosis 13,14 , Schistosoma mansoni 15 , Trypanosoma cruzi 15-17 , and Leishmania major 18. Considering the promising activity against T. cruzi and the considerable amounts of licarin A isolated from the leaves of Nectandra oppositifolia (Lauraceae), this compound was selected for preparation of semi-synthetic analogues to further pharmacophore exploitation. Thereafter, licarin A was obtained in pure form and five semi-synthetic and twenty-one analogues were designed by the molecular simplification approach. The main objective wa...

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“…[19] Synthetic analogs of benzofuran scaffold have been synthesized and many drugs bearing this moiety are available in the market treating various diseases, a few of which are given in Figure 2. [20,21]…”

Section: Introductionmentioning

confidence: 99%

Advances in Synthetic Strategies and Medicinal Importance of Benzofurans: A Review

Dwarakanath

Gaonkar

2022

Asian J Org Chem

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Out of the many heterocycles that exhibit pharmaceutical and therapeutic properties, benzofurans remain the most eye-catching to scientists ever since their discovery. From being present in natural products to synthetic analogs they show diverse biological properties which are used to treat various diseases. Interestingly, some of the benzofuran hybrids were docked against COVID-19 Main Protease and it showed appealing results. Apart from medicinal properties it also exhibits some non-drug applications. The structure activity relationship of benzofuran derivatives in many infections draws attention to the extent where drugs can be produced in a short time span which highlights their significance in medicinal chemistry. There are considerable reaction schemes to synthesize this moiety either simple one pot reactions or multistep. Here, we emphasize on the chemistry of benzofurans, synthesis and its derivatives in the recent years, some of which show notable anti-tumor, antifungal, anti-mycobacterial and anti-oxidant activities.

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Factorial design study to access the “green” iodocyclization reaction of 2-allylphenols

Cited by 6 publications

References 8 publications

Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors with Anti-inflammatory Potential

Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors with Anti-inflammatory Potential

Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A

Advances in Synthetic Strategies and Medicinal Importance of Benzofurans: A Review

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