67387-76-2Relevant articles and documents
Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition
Abdel-Aziz, Alaa A.-M.,AlSaif, Nawaf A.,Alanazi, Mohammed M.,El-Azab, Adel S.,El-Husseiny, Walaa M.,El-Sayed, Magda A.-A.
, p. 744 - 758 (2020)
A series of 24 compounds was synthesised based on a 2-cyclopentyloxyanisole scaffold 3–14 and their in vitro antitumor activity was evaluated. Compounds 4a, 4b, 6b, 7b, 13, and 14 had the most potent antitumor activity (IC50 range: 5.13–17.95 μM), compared to those of the reference drugs celecoxib, afatinib, and doxorubicin. The most active derivatives 4a, 4b, 7b, and 13 were evaluated for their inhibitory activity against COX-2, PDE4B, and TNF-α. Compounds 4a and 13 potently inhibited TNF-α (IC50 values: 2.01 and 6.72 μM, respectively) compared with celecoxib (IC50=6.44 μM). Compounds 4b and 13 potently inhibited COX-2 (IC50 values: 1.08 and 1.88 μM, respectively) comparable to that of celecoxib (IC50=0.68 μM). Compounds 4a, 7b, and 13 inhibited PDE4B (IC50 values: 5.62, 5.65, and 3.98 μM, respectively) compared with the reference drug roflumilast (IC50=1.55 μM). The molecular docking of compounds 4b and 13 with the COX-2 and PDE4B binding pockets was studied.Highlights Antitumor activity of new synthesized cyclopentyloxyanisole scaffold was evaluated. The powerful antitumor 4a, 4b, 6b, 7b & 13 were assessed as COX-2, PDE4B & TNF-α inhibitors. Compounds 4a, 7b, and 13 exhibited COX-2, PDE4B, and TNF-α inhibition. Compounds 4b and 13 showed strong interactions at the COX-2 and PDE4B binding pockets.
Solving a scale-up problem in the 0-alkylation of isovanillin under phase-transfer catalysis conditions
Wilk, Bogdan K.,Mwisiya, Nalukui,Helom, Jean L.
, p. 785 - 786 (2008)
The alkylation of isovanillin with cyclopentyl bromide in the presence of potassium carbonate and a phase-transfer catalyst in THF is investigated. Successful completion of the reaction depends on the particle size of potassium carbonate.
Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors
Almatary, Aya M.,Elmorsy, Mohammad A.,El Husseiny, Walaa M.,Selim, Khalid B.,El-Sayed, Magda A.-A.
, (2018)
A new hybrid template was designed by combining the structural features of phosphodiesterase 4 (PDE4) inhibitors with several heterocyclic moieties which present an integral part in the skeleton of many apoptotic agents. Thirteen compounds of the synthesized hybrids displayed higher inhibitory activity against PDE4B than the reference drug, roflumilast. Further investigation indicated that compounds 13b and 20 arrested the cell cycle at the G2/M phase and the pre-G1 phase, and induced cell death by apoptosis of A549 cells in a caspase-dependent manner.
New hybrid pyrazole and imidazopyrazole antinflammatory agents able to reduce ROS production in different biological targets
Brullo, Chiara,Massa, Matteo,Rapetti, Federica,Alfei, Silvana,Bertolotto, Maria B.,Montecucco, Fabrizio,Signorello, Maria Grazia,Bruno, Olga
, (2020/02/22)
Several anti-inflammatory agents based on pyrazole and imidazopyrazole scaffolds and a large library of substituted catechol PDE4D inhibitors were reported by us in the recent past. To obtain new molecules potentially able to act on different targets involved in inflammation onset we designed and synthesized a series of hybrid compounds by linking pyrazole and imidazo-pyrazole scaffolds to differently decorated catechol moieties through an acylhydrazone chain. Some compounds showed antioxidant activity, inhibiting reactive oxygen species (ROS) elevation in neutrophils, and a good inhibition of phosphodiesterases type 4D and, particularly, type 4B, the isoform most involved in inflammation. In addition, most compounds inhibited ROS production also in platelets, confirming their ability to exert an antiinflammatory response by two independent mechanism. Structure–activity relationship (SAR) analyses evidenced that both heterocyclic scaffolds (pyrazole and imidazopyrazole) and the substituted catechol moiety were determinant for the pharmacodynamic properties, even if hybrid molecules bearing to the pyrazole series were more active than the imidazopyrazole ones. In addition, the pivotal role of the catechol substituents has been analyzed. In conclusion the hybridization approach gave a new serie of multitarget antiinflammatory compounds, characterized by a strong antioxidant activity in different biological targets.
Comparison of the full-length and 152~528 truncate of human cyclic nucleotide phosphodiesterase 4b2 for the characterization of inhibitors
Zhang, Xiang,He, Shu,Hu, Xiaolei,Wu, Jing,Li, Xinpeng,Liao, Fei,Yang, Xiaolan
, p. 49 - 58 (2019/08/06)
Aim and Objective: Human full-length cyclic nucleotide phosphodiesterase isozyme 4B2 (hPDE4B2) as the target for screening and characterizing inhibitors suffers from low activity yield and the coexistence of two conformational states bearing different aff
Novel multitarget 5-arylidenehydantoins with arylpiperazinealkyl fragment: Pharmacological evaluation and investigation of cytotoxicity and metabolic stability
Czopek, Anna,Bucki, Adam,Ko?aczkowski, Marcin,Zagórska, Agnieszka,Drop, Marcin,Paw?owski, Maciej,Siwek, Agata,G?uch-Lutwin, Monika,P?kala, El?bieta,Chrzanowska, Alicja,Struga, Marta,Partyka, Anna,Weso?owska, Anna
supporting information, p. 4163 - 4173 (2019/08/07)
On the basis of the structures of serotonin modulators or drugs (NAN-190, buspirone, aripiprazole) and phosphodiesterase 4 (PDE4) inhibitors (rolipram, RO-20-1724), a series of novel multitarget 5-arylidenehydantoin derivatives with arylpiperazine fragment was synthesized. Among these compounds, 5-(3,4-dimethoxybenzylidene-3-(4-(4-(2,3-dichlorophenyl)piperazine-1-yl)butyl)-imidazolidine-2,4-dione (13) and 5-(3-cyclopentyloxy-4-methoxybenzylidene-3-(4-(4-(2-methoxyphenyl)piperazine-1-yl)butyl)-imidazolidine-2,4-dione (18) were found to be the most promising showing very high affinity toward 5-HT1A and 5-HT7 receptors (Ki = 0.2–1.0 nM) but a negligible inhibitory effect on PDE4. The high affinity of the compounds for 5-HT1A and 5-HT7 receptors was further investigated by computer-aided studies. Moreover, compounds 13 and 18 showed no significant cytotoxicity in the MTT assay, but high clearance in the in vitro assay. In addition, these compounds behaved like 5-HT1A and 5-HT7 receptor antagonists and exhibited antidepressant-like activity, similar to the reference drug citalopram, in an animal model of depression.
Efficient synthesis of (?)-(R)- and (+)-(S)-rolipram
Kaur, Ramandeep,Pandey, Satyendra Kumar
supporting information, p. 4333 - 4335 (2017/10/17)
A novel, efficient and protecting group free enantioselective synthetic approach of (?)-(R)-1 and (+)-(S)-rolipram 2 is described employing the organocatalyzed asymmetric Michael addition, Henry condensation, Wittig olefination and reductive lactamization
N-Cyanation of Secondary Amines Using Trichloroacetonitrile
Ayres, James N.,Ling, Kenneth B.,Morrill, Louis C.
supporting information, p. 5528 - 5531 (2016/11/17)
A one-pot N-cyanation of secondary amines has been developed using trichloroacetonitrile as an inexpensive cyano source. A diverse range of cyclic and acyclic secondary amines can be readily transformed into the corresponding cyanamides in good isolated yields, with the method successfully utilized in the final synthetic step of a biologically active rolipram-derived cyanamide. This approach exhibits distinct selectivity when compared to the use of highly toxic cyanogen bromide.
Phase Transfer Catalysis with Quaternary Ammonium Type Gemini Surfactants: O-Alkylation of Isovanillin
Boz, Mesut,Ba?türk, Sedat Semih
, p. 663 - 671 (2016/07/06)
In this paper, O-alkylation of isovanillin with unusual phase transfer catalysts alkandiyl-α,ω-bis(dimethylalkylammonium bromide) dimeric surfactants (also known as gemini surfactants) is described. Some dimeric surfactants with simple hydrophobic alkyl chains and others with hydrophobic alkyl chains containing ester functionalities with different lengths were synthesized and characterized in our laboratory. The alkylation of isovanillin with alkyl halide was successively carried out in the presence of potassium carbonate and a phase transfer catalyst in tetrahydrofuran. The same reactions were also performed with both the traditional phase transfer catalyst tetrabutylammonium bromide and without any catalyst. The results were compared with those of dimeric surfactants. Consequently, it was expressed that alkandiyl-α,ω-bis(dimethylalkylammonium bromide) dimeric surfactants successively exhibit the character of phase transfer catalysts through environmentally friendly procedures under mild conditions. The most significant feature of this work is that dimeric surfactants have been determined to act as phase transfer agents.
Imidazole derivatives show anticancer potential by inducing apoptosis and cellular senescence
Sharma, Gangavaram V. M.,Ramesh, Adepu,Singh, Ashita,Srikanth, Gourishetty,Jayaram, Vankudoth,Duscharla, Divya,Jun, Jung Ho,Ummanni, Ramesh,Malhotra, Sanjay V.
, p. 1751 - 1760 (2014/12/11)
Imidazole-based compounds are attractive targets in the design of novel chemical structures for the discovery of new drugs. In the current study, we have synthesized a series of new 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles by multicomponent reaction (MCR). Vanillin and isovanillin derivatives were reacted with benzil/pyridil and diverse amines and ammonium acetate in acetic acid at 50-110 °C for 24 h to afford respective imidazoles in 55-70% yields. The series of molecules were evaluated for anti-cancer potential against the National Cancer Institute's 60 human cancer cell line panel. Preliminary screening highlighted the anticancer potential of 2,2′-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-1-isobutyl-1H-imidazole-4,5-diyl)dipyridine (NSC 771432) against different cancer cell types. A549 cells were treated in vitro to determine the mode of action of NSC 771432 on growth of these cells. This compound inhibits anchorage independent growth and cell migration, and induces cell cycle arrest in the G2/M phase. Also, the exposure of A549 cells to NSC 771432 leads to cellular senescence. This journal is
