40106-14-7Relevant academic research and scientific papers
New thiophene–acridine compounds: Synthesis, antileishmanial activity, DNA binding, chemometric, and molecular docking studies
de Lima Serafim, Vanessa,Félix, Mayara Barbalho,Frade Silva, Daiana Karla,Rodrigues, Klinger Ant?nio da Franca,Andrade, Patrícia Néris,de Almeida, Sinara M?nica Vitalino,de Albuquerque dos Santos, Sanderssonilo,de Oliveira, Jamerson Ferreira,de Lima, Maria do Carmo Alves,Mendon?a-Junior, Francisco Jaime Bezerra,Scotti, Marcus Tullius,de Oliveira, Márcia Rosa,de Moura, Ricardo Olímpio
, p. 1141 - 1155 (2018/03/28)
In this study, we synthesized eight new compounds containing the 2-amino-cycloalkyl[b]thiophene and acridine moieties (ACT01 and ACS01-ACS07). None tested compounds presented human erythrocyte cytotoxicity. The new compounds presented antipromastigote activity, where ACS01 and ACS02 derivatives presented significant antileishmanial activity, with better performance than the reference drugs (tri and pentavalent antimonials), with respective IC50 values of 9.60?±?3.19 and 10.95?±?3.96?μm. Additionally, these two derivatives were effective against antimony-resistant Leishmania (Leishmania) amazonensis strains. In addition, binding and fragmentation DNA assays were performed. It was observed that the antileishmanial activity of ACS01 is not associated with DNA fragmentation of the promastigote forms. However, it interacted with DNA with a binding constant of 104?m?1. In partial least-squares studies, it was observed that the most active compounds (ACS01 and ACS02) showed lower values of amphiphilic moment descriptor, but there was a correlation between the lipophilicity of the molecules and antileishmanial activity. Furthermore, the docking molecular studies showed interactions between thiophene–acridine derivatives and the active site of pyruvate kinase enzyme with the major contribution of asparagine 152 residue for the interaction with thiophene moiety. Thus, the results suggested that the new thiophene–acridine derivatives are promising molecules as potential drug candidates.
A green chemical approach: a straightforward one-pot synthesis of 2-aminothiophene derivatives via Gewald reaction in deep eutectic solvents
Shaabani, Ahmad,Hooshmand, Seyyed Emad,Afaridoun, Hadi
, p. 711 - 716 (2017/03/17)
Abstract: The synergic effect of choline chloride/urea as a deep eutectic solvent was investigated in the synthesis of 2-aminothiophene derivatives via a three-component cyclocondensation of a ketone or an aldehyde with activated nitriles and elemental sulfur catalyzed by NaOH as cheap and highly accessible base. The advantages of this catalytic protocol are eco-friendly, easy to set up, reusability, and a simple separation and purification of products without using chromatography in high yields at short times. Graphical abstract: [Figure not available: see fulltext.]
Antileishmanial activity of new thiophene–indole hybrids: Design, synthesis, biological and cytotoxic evaluation, and chemometric studies
Félix, Mayara B.,de Souza, Edson R.,de Lima, Maria do C.A.,Frade, Daiana Karla G.,Serafim, Vanessa de L.,Rodrigues, Klinger Antonio da F.,Néris, Patrícia Lima do N.,Ribeiro, Frederico F.,Scotti, Luciana,Scotti, Marcus T.,de Aquino, Thiago M.,Mendon?a Junior, Francisco Jaime B.,de Oliveira, Márcia R.
, p. 3972 - 3977 (2016/08/24)
In the present work, thirty-two hybrid compounds containing cycloalka[b]thiophene and indole moieties (TN5, TN5 1–7, TN6, TN6 1–7, TN7, TN7 1–7, TN8, TN8 1–7) were designed, synthesized and evaluated for their cytotoxic and antileishmanial activity against Leishmania amazonensis promastigotes. More than half of the compounds (18 compounds) exhibited significant antileishmanial activity (IC50lower than 10.0 μg/L), showing better performance than the reference drugs (tri- and penta-valent antimonials). The most active compounds were TN8-7, TN6-1 and TN7 with respective IC50values of 2.1, 2.3 and 3.2 μg/mL. Demonstrating that all of the compounds were less toxic than the reference drugs, even at the highest evaluated concentration (400 μg/mL), no compound tested presented human erythrocyte cytotoxicity. Compound TN8-7's effectiveness against a trivalent antimony-resistant culture was demonstrated. It was observed that TN8-7's antileishmanial activity is associated with DNA fragmentation of L. amazonensis promastigotes. Chemometric studies (CPCA, PCA, and PLS) highlight intrinsic solubility/lipophilicity, and compound size and shape as closely related to activity. Our results suggest that hybrid cycloalka[b]thiophene–indole derivatives may be considered as lead compounds for further development of new drugs for the treatment of leishmaniasis.
Efficient three-component Gewald reactions under Et3N/H 2O conditions
Abaee, M. Saeed,Cheraghi, Somayeh
, p. 261 - 269 (2014/04/03)
In a medium consisting of triethylamine and water, methylene ketones undergo room temperature Gewald reactions with elemental sulfur and ethyl cyanoacetate (or malononitrile) to yield 2 aminothiophene derivatives efficiently within short time periods. Because of the high polarity of the medium, products precipitate in the reaction mixtures spontaneously. This makes isolation of the products easy by simple filtration and avoids cumbersome chromatographic separations. Mechanistic studies suggest that the reactions proceed via a Knoevenagel condensation pathway(equation presented). 2013
Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3- carboxamides and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from known antimycobacterial lead
Nallangi, Radhika,Samala, Ganesh,Sridevi, Jonnalagadda Padma,Yogeeswari, Perumal,Sriram, Dharmarajan
, p. 110 - 117 (2014/03/21)
Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c] pyridine-3-carboxamide and ten of 2-substituted 4,5,6,7,8,9- hexahydrocycloocta[b]thiophene-3-carboxamide were synthesized by molecular modification of a known antimycobacterial molecule. Compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9- hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most active compound against MTB with MIC of 3.70 μM and was more potent than Ethambutol (MIC of 7.64 μM), Ciprofloxacin (MIC of 9.41 μM) and standard lead compound SID 92097880 (MIC of 9.15 μM). Compound 12f also showed MTB MIC of 1.23 μM in the presence of an efflux pump inhibitor verapamil, and showed no cytotoxicity at 50 μM.
Solvent-free synthesis of 2-aminothiophene-3-carbonitrile derivatives using high-speed vibration milling
Xu, Fang,Li, Yujin,Xu, Fengshuang,Ye, Qing,Han, Liang,Gao, Jianrong,Yu, Wubin
, p. 450 - 452 (2014/08/05)
The solvent-free synthesis of 2-aminothiophene-3-carbonitrile derivatives by high-speed vibration milling using the inexpensive and environmentally friendly Et2NH as a catalyst was studied. The reaction conditions were optimised and the derivatives were obtained in good yield. This method has advantages in terms of short reaction time and facile conditions.
The synthesis and biological evaluation of 2-amino-4,5,6,7,8,9- hexahydrocycloocta[b]thiophenes as allosteric modulators of the A1 adenosine receptor
Aurelio, Luigi,Christopoulos, Arthur,Flynn, Bernard L.,Scammells, Peter J.,Sexton, Patrick M.,Valant, Celine
supporting information; experimental part, p. 3704 - 3707 (2011/08/06)
A series of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes were prepared and evaluated as potential allosteric modulators of the A1 adenosine receptor (AR). The structure-activity relationships of the 3-position were explored along with va
Convenient synthesis of 2-aminothiophene derivatives by acceleration of gewald reaction under ultrasonic aqueous conditions
Mojtahedi, Mohammad M.,Abaee, M. Saeed,Mahmoodi, Peyman,Adib, Mehdi
experimental part, p. 2067 - 2074 (2010/08/13)
Under ultrasound irradiation and in the presence of H2O/Et 2NH, ethyl cyanoacetate or malononitrile can combine with-methylene carbonyl compounds and elemental sulfur to efficiently yield 2-aminothiophene derivatives within a few minutes. Products are easily obtained by simple filtration because of their spontaneous precipitation in the reaction mixtures. Copyright Taylor & Francis Group, LLC.
Synthesis of new derivatives of thieno[2,3-b]pyridine fused with octyl ring
Al-Omran, Fatima A.,El-Khair, Adel A.
, p. 561 - 568 (2008/09/16)
(Chemical Equation Presented) Derivatives of thiophene, thieno[2,3-b]pyridine, thieno[5′,4′:4,5]pyrimido[3,2-a]pyridine and thiepine fused with octyl ring have been synthesized and tested for antimicrobial and antifungal activities. The structure of the newly synthesized compounds have been established on the basis of their analytical and spectral data.
Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes
Sridhar, Madabhushi,Rao, Rayankula Mallikarjuna,Baba, Nanduri H.K.,Kumbhare, Ravindra M.
, p. 3171 - 3172 (2007/10/03)
Microwave-promoted synthesis of 2-aminothiophenes by multicomponent reactions of a ketone with an active nitrile and elemental sulfur under KF-alumina catalysis is described.
