41335-57-3Relevant academic research and scientific papers
A General Approach to Sequence-Controlled Polymers Using Macrocyclic Ring Opening Metathesis Polymerization
Gutekunst, Will R.,Hawker, Craig J.
, p. 8038 - 8041 (2015)
A new and general strategy for the synthesis of sequence-defined polymers is described that employs relay metathesis to promote the ring opening polymerization of unstrained macrocyclic structures. Central to this approach is the development of a small molecule "polymerization trigger" which when coupled with a diverse range of sequence-defined units allows for the controlled, directional synthesis of sequence controlled polymers.
HYDROSILYLATION AND HYDROGERMYLATION OF 3-OXO-1,2-BENZISOTHIAZOLINE-2-(2-PROPYNYL)-1,1-DIOXIDE
Lyashchenko, G. S.,Medvedeva, A. S.,Safronova, L. P.,Bannikova, O. B.,Voronkov, M. G.
, p. 2520 - 2523 (1991)
The addition of triethylsilane and triethylgermane to N-propargylsaccharin in the presence of the Speier catalyst gives the gem adduct with trans configuration.This pathway accounts for 75-80percent of the reaction.
One-pot four-component tandem synthesis of novel sulfonamide-1, 2, 3-triazoles catalyzed by reusable copper (II)-adsorbed on mesoporous silica under ultrasound irradiation
Arsalane, Said,Arshad, Suhana,Bougrin, Khalid,Driowya, Mohsine,El Hamidi, Adnane,Karrouchi, Khalid,Mourhly, Asmae,Tachallait, Hamza,Talha, Aicha
, (2021/07/09)
A green and efficient synthesis of new sulfonamide-1,2,3-triazoles 5 in heterogeneous conditions has been developed. The procedure involved one-pot four-component tandem sulfonamidation/azidation/1,3-dipolar cycloaddition (1,3-DC) reactions under a cooperative effect of ultrasound irradiation and Cu (II) supported on amorphous mesoporous silica [mSiO2-Cu (II)] catalysis at room temperature in aqueous medium. In addition, the 1,4-disubstituted 1,2,3-triazoles 5 were synthesized by regioselective and chemoselective methods to afford the pure products in excellent yields and short reaction times under ultrasonic irradiation. The supported catalyst has been prepared from copper (II) nitrate by simple method using ultrasound activation and characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method and Barrett-Joyner-Halenda (BJH) method. Also, the catalyst is easily prepared, stable, efficient, selective, and reusable under ultrasonic conditions.
1,3-Dipolar Cycloaddition, HPLC Enantioseparation, and Docking Studies of Saccharin/Isoxazole and Saccharin/Isoxazoline Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors
D'Ascenzio, Melissa,Secci, Daniela,Carradori, Simone,Zara, Susi,Guglielmi, Paolo,Cirilli, Roberto,Pierini, Marco,Poli, Giulio,Tuccinardi, Tiziano,Angeli, Andrea,Supuran, Claudiu T.
, p. 2470 - 2488 (2020/03/31)
Two series of saccharin/isoxazole and saccharin/isoxazoline hybrids were synthesized by 1,3-dipolar cycloaddition. The new compounds showed to be endowed with potent and selective inhibitory activity against the cancer-related human carbonic anhydrase (hCA) IX and XII isoforms in the nanomolar range, while no affinity was encountered for off-targets, such as hCA I and II. Successive enantioseparation on a milligram scale of the most representative compounds led to the discovery that (S)-isomers were more potent than their corresponding (R)-enantiomers. Lastly, molecular modeling studies were conducted to define those structural requirements that were responsible for the discrimination among selected human isoforms of carbonic anhydrases. Two nanomolar hCA IX and XII inhibitors were also screened for their selective toxicity against non tumoral primary cells (fibroblasts) and against a breast adenocarcinoma cell line (MCF7) in hypoxic environment. The efficacious combination of these compounds with doxorubicin on MCF7 cells was demonstrated after 72 h of treatment.
Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation
Guglielmi, Paolo,Rotondi, Giulia,Secci, Daniela,Angeli, Andrea,Chimenti, Paola,Nocentini, Alessio,Bonardi, Alessandro,Gratteri, Paola,Carradori, Simone,Supuran, Claudiu T.
, p. 1891 - 1905 (2020/10/06)
A large library of saccharin and acesulfame derivatives has been synthesised and evaluated against four isoforms of human carbonic anhydrase, the two off-targets hCA I/II and the tumour related isoforms hCA IX/XII. Different strategies of scaffold modification have been attempted on both saccharin as well as acesulfame core leading to the obtainment of 60 compounds. Some of them exhibited inhibitory activity in the nanomolar range, albeit some of the performed changes led to either micromolar activity or to its absence, against hCA IX/XII. Molecular modelling studies focused the attention on the binding mode of these compounds to the enzyme. The proposed inhibition mechanism is the anchoring to zinc-bound water molecule. Docking studies along with molecular dynamics also underlined the importance of the compounds flexibility (e.g. achieved through the insertion of methylene group) which favoured potent and selective hCA inhibition.
Design, synthesis, and in silico studies of novel eugenyloxy propanol azole derivatives having potent antinociceptive activity and evaluation of their β-adrenoceptor blocking property
Behrouz, Somayeh,Soltani Rad, Mohammad Navid,Taghavi Shahraki, Bahareh,Fathalipour, Mohammad,Behrouz, Marzieh,Mirkhani, Hossein
, p. 147 - 164 (2018/08/22)
The design, synthesis, antinociceptive and β-adrenoceptor blocking activities of several eugenyloxy propanol azole derivatives have been described. In this synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4 which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to obtain the corresponding azide 6. The ‘Click’ Huisgen cycloaddition reaction of 6 with diverse alkynes afforded the title compounds in good yields. The synthesized eugenyloxy propanol azole derivatives were in vivo studied for the acute antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f, 5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol as a standard drug. In addition, all compounds were ex vivo tested for β-adrenoceptor blocking properties on isolated left atrium of male rats which exhibited partial antagonist or agonist behaviour compared to the standard drugs. The molecular docking study on the binding site of transient receptor potential vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy propanol azole analogues exhibited the strong affinity to bind at site of TPRV1 in a “tail-up, head-down” conformation and the presence of triazolyl moieties has played undeniable role in durable binding of these ligands to TRPV1. The in silico pharmacokinetic profile, drug likeness and toxicity predictions carried out for all compounds determined that 5g can be considered as potential antinociceptive drug candidate for future research.
Design, synthesis and evaluation of N-substituted saccharin derivatives as selective inhibitors of tumor-associated carbonic anhydrase XII
D'Ascenzio, Melissa,Carradori, Simone,De Monte, Celeste,Secci, Daniela,Ceruso, Mariangela,Supuran, Claudiu T.
, p. 1821 - 1831 (2014/03/21)
A series of N-alkylated saccharin derivatives were synthesized and tested for the inhibition of four different isoforms of human carbonic anhydrase (CA, EC 4. 2.1.1): the transmembrane tumor-associated CA IX and XII, and the cytosolic CA I and II. Most of the reported derivatives inhibited CA XII in the nanomolar/low micromolar range, hCA IX with KIs ranging between 11 and 390 nM, whereas they were inactive against both CA I (KIs >50 μM) and II (KIs ranging between 39.1 nM and 50 μM). Since CA I and II are off-targets of antitumor carbonic anhydrase inhibitors (CAIs), the obtained results represent an encouraging achievement for the development of new anticancer candidates without the common side effects of non-selective CAIs. Moreover, the lack of an explicit zinc binding function on these inhibitors opens the way towards the exploration of novel mechanisms of inhibition that could explain the high selectivity of these compounds for the inhibition of the transmembrane, tumor-associated isoforms over the cytosolic ones.
1,4-Dihydroxyanthraquinone-copper(II) nanoparticles immobilized on silica gel: A highly efficient, copper scavenger and recyclable heterogeneous nanocatalyst for a click approach to the three-component synthesis of 1,2,3-triazole derivatives in water
Sharghi, Hashem,Khoshnood, Abbas,Doroodmand, Mohammad Mahdi,Khalifeh, Reza
experimental part, p. 231 - 250 (2012/09/11)
High yielding preparation of structurally different β-hydroxy 1,4-disubstituted 1,2,3-triazole from the regio-selective reaction of epoxides 2a-2c with wide range of terminal alkynes 1a-1j, and sodium azide in the presence of catalytic amount, complexed form of homogeneous catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II)] (5.0 mol%), [AQ 2Cu(II)] 7 at 25 °C in water has been described. To benefit from the recovery and reuse of the catalyst, a novel heterogeneous nanoparticles of catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II) aminopropyl silica gel] (5.0 mol%), [AQ2Cu(II)-APSiO2] 13 bearing oxygen anthraquinone ligands with strong copper(II) affinity was easily prepared by using silica gel as a suitable support. The heterogeneous catalyst was fully characterized by XRD, SEM, AFM, ICP, TG methods for analysis of nitrogen adsorption, and FT-IR techniques. The remarkable features of this protocol are high yields, short reaction times, a cleaner reaction profile in an environmentally benign solvent (H2O), one-pot procedure and the method is applicable to large-scale operation without any problem. Furthermore, the catalyst could be recovered and easily removed by simple filtration of the reaction mixture and it was recycled ten times showing negligible copper leaching. In their uncomplexed form of homogeneous catalyst [AQ 2Cu(II)] 7 and heterogeneous catalyst [AQ2Cu(II)- APSiO2] 13, the anthraquinone ligand 6 and [AQ-APSiO2] 12 are very efficient copper scavengers able to catalyze the 1,3-dipolar cycloaddition reaction of azides with alkynes (CuAAC) without pre-synthesis of catalysts.
An efficient one-step regiospecific synthesis of novel isoxazolines and isoxazoles of N-substituted saccharin derivatives through solvent-free microwave-assisted [3+2] cycloaddition
Mabrour, Mahmoud,Bougrin, Khalid,Benhida, Rachid,Loupy, André,Soufiaoui, Mohamed
, p. 443 - 447 (2008/02/04)
Novel isoxazolines and isoxazoles of N-substituted saccharin derivatives are synthesized in good yields by 1,3-dipolar cycloaddition of N-allyl or propargyl N-substituted saccharin with arylnitrile oxide under solvent-free microwave irradiation. In this process, the yields were significantly improved over conventional heating, without alteration of the selectivity. The regioselectivity as well as the nonthermal specific microwave effect are discussed.
