122-60-1Relevant academic research and scientific papers
Sustainable Synthesis of a Potent and Selective 5-HT7Receptor Antagonist Using a Mechanochemical Approach
Canale, Vittorio,Frisi, Valeria,Bantreil, Xavier,Lamaty, Frédéric,Zajdel, Pawe?
, p. 10958 - 10965 (2020)
A mechanochemical procedure was developed to obtain PZ-1361, a potent and selective 5-HT7 receptor antagonist, with antidepressant properties in rodents. The elaborated protocol offered several advantages over classical batch synthesis, including improvement of the overall yield (from 34% to 64%), reduction of reaction time (from 60 to 5.5 h), limitation of the use of toxic solvents, and the formation of byproducts. This approach represents a rare example of the synthesis of biologically active compounds exclusively performed using mechanochemical reactions.
Discovery of selective dopamine D4 receptor antagonists: 1-aryloxy-3-(4-aryloxypiperidinyl)-2-propanols
Wright, Jon L.,Gregory, Tracy F.,Heffher, Thomas G.,MacKenzie, Robert G.,Pugsley, Thomas A.,Vander Meulen, Seth,Wise, Lawrence D.
, p. 1377 - 1380 (1997)
High volume screening identified 3-(4-benzylpiperidinyl)- 1-naphthoxy-2-propanol as a selective dopamine D4 receptor ligand. A systematic structure-activity study revealed that the benzyl group could be replaced with phenoxy and the naphthalene with phenyl to improve potency almost tenfold. The (R) enantiomer of this compound had a D4 affinity of 2 nM and was over 100-fold weaker at dopamine D2 and D3 receptors.
A facile and efficient method for synthesis of β-iodocarboxylates from terminal epoxides
Zhu, Ye-Fu,Wei, Bo-Le,Wang, Wen-Qiong,Xuan, Li-Jiang
, (2019)
A facile and efficient method has been developed for synthesis of β-iodocarboxylates in the presences of Ph3P/I2. Starting from epoxides, a series of β-iodocarboxylate compounds can be directly obtained in toluene media with excellent yields. Moreover, the method was successfully applied for the late-stage modification of natural products, such as isosteviol and vincamine derivatives, achieving the corresponding β-iodocarboxylates in good yields.
Rhenium catalysed epoxidations with hydrogen peroxide: Tertiary arsines as effective cocatalysts
Van Vliet, Michiel C.A.,Arenas, Isabel W.C.E.,Sheldon, Roger A.
, p. 377 - 380 (2000)
Perrhenic acid in combination with tertiary arsines gives a versatile catalytic system for epoxidation of alkenes with hydrogen peroxide. The best results are obtained with diphenylmethylarsine. A wide range of alkenes could be epoxidised with aqueous hydrogen peroxide (60%) in 60-100% yields with substrate to catalyst ratios of up to 1000. The Royal Society of Chemistry 2000.
A novel method for synthesis of aryl glycidyl ethers
Liu,Chen,Cao,Li
, p. 833 - 838 (1994)
A solid-liquid phase-transfer catalytic method for the synthesis of aryl glycidyl ethers has been described, and the factors affecting the reaction yield have been examined.
Selective epoxidation of olefins by hydrogen peroxide in water using a polyoxometalate catalyst supported on chemically modified hydrophobic mesoporous silica gel
Sakamoto,Pac
, p. 10009 - 10012 (2000)
A new heterogeneous catalyst prepared by immobilisation of polyoxometalates on chemically modified hydrophobic mesoporous silica gel has been successfully applied to the selective epoxidation of olefins with 15% aqueous H2O2 without the use of organic solvent. (C) 2000 Elsevier Science Ltd.
Microwave enhanced synthesis of epoxypropoxyphenols
Khadilkar, Bhushan M.,Bendale, Pravin M.
, p. 2051 - 2056 (1997)
Phenols were condensed with epichlorohydrin under microwave irradiation. Dramatic reduction in reaction time was observed with excellent yields.
Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites
Babbar, Palak,Das, Pronay,Manickam, Yogavel,Mankad, Yash,Yadav, Swati,Parvez, Suhel,Sharma, Amit,Reddy, D. Srinivasa
, p. 1777 - 1794 (2021/05/10)
Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics. Co-crystallization of the most potent compound in our series (CL-2) with PfKRS revealed its structural basis of enzymatic binding and potency. Further, we report that CL-2 has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.
Discovery of a Potent and Selective Chikungunya Virus Envelope Protein Inhibitor through Computer-Aided Drug Design
álvarez, Diego E.,Battini, Leandro,Bollini, Mariela,Fidalgo, Daniela M.
, p. 1503 - 1518 (2021/06/28)
The worldwide expansion of chikungunya virus (CHIKV) into tropical and subtropical areas in the last 15 years has posed a currently unmet need for vaccines and therapeutics. The E2-E1 envelope glycoprotein complex binds receptors on the host cell and promotes membrane fusion during CHIKV entry, thus constituting an attractive target for the development of antiviral drugs. In order to identify CHIKV antivirals acting through inhibition of the envelope glycoprotein complex function, our first approach was to search for amenable druggable sites within the E2-E1 heterodimer. We identified a pocket located in the interface between E2 and E1 around the fusion loop. Then, via a structure-based virtual screening approach and in vitro assay of antiviral activity, we identified compound 7 as a specific inhibitor of CHIKV. Through a lead optimization process, we obtained compound 11 that demonstrated increased antiviral activity and low cytotoxicity (EC50 1.6 μM, CC50 56.0 μM). Molecular dynamics simulations were carried out and described a possible interaction pattern of compound 11 and the E1-E2 dimer that could be useful for further optimization. As expected from target site selection, compound 11 inhibited virus internalization during CHIKV entry. In addition, virus populations resistant to compound 11 included mutation E2-P173S, which mapped to the proposed binding pocket, and second site mutation E1-Y24H. Construction of recombinant viruses showed that these mutations conferred antiviral resistance in the parental background. Finally, compound 11 presents acceptable solubility values and is chemically and enzymatically stable in different media. Altogether, these findings uncover a suitable pocket for the design of CHIKV entry inhibitors with promising antiviral activity and pharmacological profiles.
Facile microwave-assisted synthesis and antitubercular evaluation of novel aziridine derivatives
Sarojini, Perumal,Jeyachandran, Malaichamy,Sriram, Dharmarajan,Ranganathan, Palraj,Gandhimathi
, (2021/02/26)
Novel 2-(aryloxymethyl)aziridines and 2-((3-aryl-1-phenylallyloxy)methyl)aziridine derivatives were prepared via ring-opening reaction of epoxides. The synthesized derivatives were characterized by using elemental analysis (EA), FT-IR, 13C NMR, and 1H NMR. The in vitro antitubercular activities of the synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB H37Rv) strain using MTT-MABA assay. All the aziridine derivatives exhibited improved persuasive antitubercular activity against MTB H37Rv in comparison with standard drugs. Among the tested compounds, 2-(naphthalene-1-yloxy) methyl aziridine (5b), 2-(naphthalene-2-yloxy)methylaziridine (5c), 2-(m-tolyloxymethyl)aziridine (5e), 2-(3-(4-methoxyphenyl)-1-phenylalloxy)methylaziridine (12b) and 2-(3-(2-chlorophenyl)-1-phenylallyloxy)methylaziridine (12c) revealed promising activity against MTB H37Rv. Specifically, compound 5b and 12 b showed three-times more active (MIC = 0.5 μg/mL) than the standard drugs ethambutol (MIC = 1.56 μg/mL) and ciprofloxacin (MIC = 1.56 μg/mL).
