205381-75-5Relevant academic research and scientific papers
Aryloxyethyl thiocyanates are potent growth inhibitors of Trypanosoma cruzi and Toxoplasma gondii
Chao, María N.,Matiuzzi, Carolina Exeni,Storey, Melissa,Li, Catherine,Szajnman, Sergio H.,Docampo, Roberto,Moreno, Silvia N. J.,Rodriguez, Juan B.
, p. 1094 - 1108 (2015/06/08)
Abstract As a part of our project aimed at searching for new safe chemotherapeutic agents against parasitic diseases, several compounds structurally related to the antiparasitic agent WC-9 (4-phenoxyphenoxyethyl thiocyanate), which were modified at the te
Synthesis and structure-activity relationships of varied ether linker analogues of the antitubercular drug (6 S)-2-nitro-6-{[4-(trifluoromethoxy) benzyl]oxy}-6,7-dihydro-5 H -imidazo[2,1- b ][1,3]oxazine (PA-824)
Thompson, Andrew M.,Sutherland, Hamish S.,Palmer, Brian D.,Kmentova, Iveta,Blaser, Adrian,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Denny, William A.
body text, p. 6563 - 6585 (2011/12/02)
New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both α-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.
Synthesis of a new class of difunctional tetraphenylene crown ethers
Gibson, Harry W.,Nagvekar, Devdatt S.,Delaviz, Yadollah,Bryant, William S.
, p. 1429 - 1436 (2007/10/03)
Three new substituted tetraphenylene crown ethers have been made. Bis(5- carbomethoxy-1,3-phenylene)-bis(p-phenylene)-(3x + 6)-crown-x, where x = 12, 16, and 20 (11b-11d) were synthesized via [1 + 1] cyclization of methyl 3,5- bis[ω-chloro(oligoethyleneoxy)]benzoates (13b-3d) with methyl 3,5-bis[ω- (p-hydroxyphenoxy)(oligoethyleneoxy)]benzoates (16b-6d) using K2CO3 as base and tetrabutylammonium iodide as a phase transfer agent in dimethylformamide (DMF). The corresponding 30-membered (x = 8) macrocycle 11a could not be made by this approach; only the elimination product, 3,5-bis(vinyloxy)benzoic acid (19), was isolated. 16a-16d were made via alkylation of p-benzyloxyphenol (14) with 13a-13d, respectively, followed by hydrogenolysis with Pd/C as catalyst. No complexation of these macrocycles with dibenzylammonium ions was detected by NMR spectroscopy, but weak complexation of 11d with a paraquat derivative was observed.
Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi
Cinque, Güendalina M.,Szajnman, Sergio H.,Zhong, Li,Docampo, Roberto,Schvartzapel, Andrea J.,Rodriguez, Juan B.,Gros, Eduardo G.
, p. 1540 - 1554 (2007/10/03)
Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at file polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC500 of 2.2 μM. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.
