23560-70-5Relevant academic research and scientific papers
Synthesis, characterization, and biologic activity of new acyl hydrazides and 1,3,4-oxadiazole derivatives
Bleotu, Coralia,Diaconu, Carmen Cristina,Hanganu, Anamaria,Ionita, Petre,Limban, Carmen,Matei, Lilia,Nemes, Roxana Maria,Nicolau, Ioana,Nuta, Diana Camelia,P?un, Anca,Radulescu, Cristiana,Tatibou?t, Arnaud,Zarafu, Irina
, (2020/08/28)
Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti-Mycobacterium tuberculosis effects) was proved by 9. Compounds 7, 8, and 9 determined blocking of G1 phase. Compound 7 proved to be toxic, inducing apoptosis in 54percent of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound 9 had the best antibacterial activity, being used as a disinfectant agent. Compounds 7, 8, and 9, seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.
Iron(II) promoted direct synthesis of dibenzo[b,e]oxepin-11(6H)-one derivatives with biological activity. A short synthesis of doxepin
Scoccia, Jimena,Castro, M. Julia,Faraoni, M. Belén,Bouzat, Cecilia,Martín, Víctor S.,Gerbino, Darío C.
supporting information, p. 2913 - 2922 (2017/04/26)
A novel and efficient synthesis of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular ortho-acylation from readily available 2-(phenoxymethyl)benzoic acids was developed. The method takes advantage of a newly developed cooperative system consisting of sustainable FeCl2 and Cl2CHOCH3 as the key components. This methodology is compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The synthetic application of new protocol was extended to the synthesis of known tricyclic drug doxepin as well as a small library of oxepin based derivatives. For the first time, the obtained dibenzo[b,e]oxepinone derivatives were evaluated for their biological activities on the free-living nematode Caenorhabditis elegans as an effective and cost-efficient model system for anthelmintic discovery.
Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other selected GPCRs
Naporra, Franziska,Gobleder, Susanne,Wittmann, Hans-Joachim,Spindler, Julia,Bodensteiner, Michael,Bernhardt, Günther,Hübner, Harald,Gmeiner, Peter,Elz, Sigurd,Strasser, Andrea
, p. 610 - 625 (2016/10/12)
Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H1/H4 receptor ligand (pKi: 8.11 (human H1R (hH1R)), 7.55 (human H4R (hH4R))), four known and 28 new oxazepine and related oxepine derivatives were synthesised and pharmacologically characterized at histamine receptors and selected aminergic GPCRs. In contrast to the oxazepine series, within the oxepine series, the new compounds showed high affinity to the hH1R (pKi: 6.8–8.7), but no or moderate affinity to the hH4R (pKi: ≤ 5.3). For one oxepine derivative (1-(2-Chloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were separated and the R-enantiomer was identified as the eutomer at the hH1R (pKi: 8.83 (R), 7.63 (S)) and the guinea-pig H1R (gpH1R) (pKi: 8.82 (R), 7.41 (S)). Molecular dynamic studies suggest that the tricyclic core of the compounds is bound in a similar mode into the binding pocket, as described for doxepine in the hH1R crystal structure. Moreover, docking studies of all oxepine derivatives at the hH1R indicate that the oxygen and the position of the chlorine in the tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the same range as to hH1R or hH4R, thus, those compounds have to be classified as dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH1/h5-HT2A receptor ligand (pKi: 9.23 (hH1R), 8.74 (h5-HT2AR), ≤7 at other analysed GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective hH1R antagonist (pKi: 8.44 (hH1R), ≤6.7 at other analyzed GPCRs). Thus, the pharmacological results suggest that the oxazepine/oxepine moiety and additionally the chlorine substitution pattern toggles receptor selectivity and specificity.
Synthesis and evaluation of biological and nonlinear optical properties of some novel 2,4-disubstituted [1,3]-thiazoles carrying 2-(aryloxymethyl)-phenyl moiety
Naveena, Channamata Shankar,Poojary, Boja,Arulmoli, Thangavelu,Manjunatha, Kumshi,Prabhu, Ashwatanarayana,Kumari, Nalilu Sucheta
, p. 1925 - 1937 (2013/07/26)
A series of 2,4-disubstituted-[1,3]-thiazoles (4a-p and 6a-l) was synthesized from 2-(aryloxymethyl)benzoic acids (1a-d) through a multistep reaction sequence in good yield. The structures of the new compounds were established on the basis of their elemen
Synthesis and biological evaluation of some [1,2,4]triazolo[3,4-b][1,3,4] thiadiazoles and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines
Naveenaa, Channamata Shankara,Poojary, Boja,Chandrashekhar, Chikkanna,Kumari, Nalilu Suchetha
experimental part, p. 189 - 200 (2012/02/14)
The reaction of 2-(aryloxymethyl)benzoic acid hydrazide with carbon disulfide in the presence of potassium hydroxide followed by hydrazine hydrate afforded 4-amino-3{2-(aryloxymethyl)pheny}[1,2,4]triazole-5-thiol (5a-d). The cyclo-condensation of 5a-d with various aromatic carboxylic acids in the presence of phosphorous oxychloride and with phenacyl bromides afforded two series of fused heterocycles namely; 6-substituted-3-{2-(aryloxymethyl)phenyl}- 1,2,4- triazolo[3,4-b][1,3,4]thiadizoles (6a-t) and 6-substituted-3-{2- (aryloxymethyl)phenyl)}[1,2,4]triazolo[3,4-b][1,3,4] thiadiazines (7a-p) respectively. The structures of these newly synthesized compounds were established on the basis of their IR, 1H-NMR 13C-NMR and Mass spectral data. All the title compounds were screened for their antimicrobial and antiinflammatory activities. Preliminary results indicated that some of them exhibit promising activities and they deserve more consideration as potential antimicrobial and anti-inflammatory agents.
Synthesis, characterization and antimicrobial activity of some disubstituted 1,3,4-oxadiazoles carrying 2-(aryloxymethyl)phenyl moiety
Naveena, Channamata Shankara,Boja, Poojary,Kumari, Nalilu Sucheta
experimental part, p. 4708 - 4719 (2010/11/16)
Disubstituted 1,3,4-oxadaiazoles (4a-z, 4a′-f′), Mannich bases (6a-p) and S-alkylated derivatives (7a-t) have been synthesized from 2-(aryloxymethyl)benzoic acids (1a-d) through a multi-step reaction sequence. The structures of new compounds were established on the basis of their elemental analyses, IR, 1H NMR, 13C NMR and mass spectral data. All the synthesized compounds were screened for their in vitro antibacterial and antifungal activity and some of them exhibited good activity.
Antimicrobial activity of some new thioureides derived from 2-(4-chlorophenoxymethyl)benzoic acid
Limban, Carmen,Chifiriuc, Mariana-Carmen Balotescu,Missir, Alexandru-Vasile,Chirita, Ileana Cornelia,Bleotu, Coralia
, p. 567 - 580 (2008/09/18)
We report here the characterisation of eight newly synthesized thioureides of 2-(4-chlorophenoxymethyl)-benzoic acid and the evaluation of the in vitro antimicrobial activity of the new compounds against Gram-positive [Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis], Gram-negative [Psedomonas aeruginosa, Escherichia coli, Salmonella enteritidis], as well as Candida spp., using both reference and clinical multidrug resistant strains to establish the minimal inhibitory concentration (MIC) values. Our results showed that the tested compounds exhibited specific antimicrobial activities, both concerning the spectrum of antimicrobial activity and the corresponding MIC values, which ranged widely between 1024 and 32 μg/mL, depending on the nature and position of the substituents on the benzene ring. The most active compounds were N-[2-(4-chlorophenoxymethyl)-benzoyl]-N′-(2,6- dichlorophenyl)-thiourea (5g) and N-[2-(4-chlorophenoxymethyl)-benzoyl]- N′-(4-bromophenyl)-thiourea (5h), which showed a broad spectrum of antimicrobial activity against enterobacterial strains (E. coli and S. enteritidis), P. aeruginosa, S. aureus and Candida spp. All the tested compounds except 5f were highly active against S. aureus (MIC=32 μg/mL), suggesting their possible use in the treatment of MRSA infections. Four of compounds also exhibited antifungal activity (MIC =256-32 μg/mL) against C. albicans, but L. monocytogenes as well as B. subtilis were resistant to all tested compounds. Our studies thus demonstrated that among other biological activities, the thioureides of 2-(4-chlorophenoxymethyl)-benzoic acid also exhibit selective and effective antimicrobial properties that could lead to the selection and use of these compounds as efficient antimicrobial agents, especially for the treatment of multidrug resistant infections.
4-Aminoquinolines: Novel nociceptin antagonists with analgesic activity
Shinkai,Ito,Iida,Kitao,Yamada,Uchida
, p. 4667 - 4677 (2007/10/03)
Small-molecule nociceptin antagonists were synthesized to examine their therapeutic potential. After a 4-aminoquinoline derivative was found to bind with the human ORL1 receptor, a series of 4-aminoquinolines and related compounds were synthesized and their binding was evaluated. Elucidation of structure - Activity relationships eventually led to the optimum compounds. One of these compounds, N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)benzamide hydrochloride (11) not only antagonized nociceptin-induced allodynia in mice but also showed analgesic effect in a hot plate test using mice and in a formalin test using rats. Its analgesic effect was not antagonized by the opioid antagonist naloxone. These results indicate that this nociceptin antagonist has the potential to become a novel type of analgesic that differs from μ-opioid agonists.
