74668-74-9Relevant academic research and scientific papers
BIARYLTRIAZOLE INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR
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Page/Page column 151-152, (2016/09/22)
The present disclosure describes biaryl triazole compounds, as well as their compositions and methods of use. The compounds inhibit the activity of macrophage migration inhibitory factor and are useful for the treatment of diseases, e.g., inflammatory dis
Design, synthesis, and protein crystallography of biaryltriazoles as potent tautomerase inhibitors of macrophage migration inhibitory factor
Dziedzic, Pawel,Cisneros, José A.,Robertson, Michael J.,Hare, Alissa A.,Danford, Nadia E.,Baxter, Richard H. G.,Jorgensen, William L.
supporting information, p. 2996 - 3003 (2015/03/18)
Optimization is reported for biaryltriazoles as inhibitors of the tautomerase activity of human macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with numerous inflammatory diseases and cancer. A combined approach was taken featuring organic synthesis, enzymatic assaying, crystallography, and modeling including free-energy perturbation (FEP) calculations. X-ray crystal structures for 3a and 3b bound to MIF are reported and provided a basis for the modeling efforts. The accommodation of the inhibitors in the binding site is striking with multiple hydrogen bonds and aryl-aryl interactions. Additional modeling encouraged pursuit of 5-phenoxyquinolinyl analogues, which led to the very potent compound 3s. Activity was further enhanced by addition of a fluorine atom adjacent to the phenolic hydroxyl group as in 3w, 3z, 3aa, and 3bb to strengthen a key hydrogen bond. It is also shown that physical properties of the compounds can be modulated by variation of solvent-exposed substituents. Several of the compounds are likely the most potent known MIF tautomerase inhibitors; the most active ones are more than 1000-fold more active than the well-studied (R)-ISO-1 and more than 200-fold more active than the chromen-4-one Orita-13.
Heteroaryl cross-coupling as an entry toward the synthesis of lavendamycin analogues: A model study
Verniest, Guido,Wang, Xingpo,De Kimpe, Norbert,Padwa, Albert
experimental part, p. 424 - 433 (2010/03/30)
(Chemical Equation Presented) ABC analogues of the antitumor antibiotic lavendamycin, which contain the key metal chelation site and redox-active quinone unit essential for biological activity, were prepared via the palladium(0)-catalyzed cross-coupling reaction of various 2-haloheteroaromatics with 2-stannylated pyridines and quinolines. Using the Stille reaction, 2-bromo substituted quinolines and 1-bromoisoquinolines were found to undergo efficient coupling with 2-pyridinylstannanes to provide unsymmetrical heterobiaryl derivatives. While the Stille reaction using the reverse coupling partners (i.e., 2-quinolinylstannanes and haloheteroaromatics) had not received much attention in the literature, we found that this alternative coupling reaction efficiently provided several new heterobiaryl derivatives. The gold-catalyzed intramolecular cycloisomerization of N-(prop-2-ynyl)-1H-indole-2-carboxamide smoothly afforded a β-carbolinone derivative that was subsequently used for a Pd(0)-catalyzed cross-coupling directed toward the synthesis of lavendamycin analogues.
Preparation of new 3-hydroxyquinoline alkaloid, jineol and its ether derivatives using directed ortho-lithiation of chloroquinoline as the key step
Tagawa, Yoshinobu,Yamashita, Hiroyuki,Nomura, Manami,Goto, Yoshinobu
, p. 2379 - 2387 (2007/10/03)
A new alkaloid, jineol (3,8-dihydroxyquinoline) was conveniently prepared employing directed ortho-lithiation of chloroquinoline for 3-position of quinoline ring. Moreover, the ether derivatives of jineol were obtained by the reaction of jineol with alkyl
5-HT1 and 5-HT2 Binding Characteristics of Some Quipazine Analogues
Glennon, Richard A.,Slusher, R. M.,Lyon, Robert A.,Titeler, Milt,McKenney, J. D.
, p. 2375 - 2380 (2007/10/02)
Arylpiperazines, such as 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and its chloro analogue mCPP, are 5-HT1 agonists, whereas quipazine, i.e., 2-(1-piperazino)quinoline, appears to be a 5-HT2 agonist.Radioligand binding studies using rat cortical membrane homogenates and drug discrimination studies using rats trained to discriminate a 5-HT1 agonist (i.e., TFMPP) or a 5-HT2 agonist (i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline reveal that quipazine and its 1-deaza analogue 2-naphthylpiperazine (2-NP) bind at 5-HT1 and 5-HT2 sites but produce stimulus effects similar to those of DOM.A structurally related compound, 1-naphthylpiperazine (1-NP), possesses a high affinity for 5-HT1 (Ki = 5 nM) and 5-HT2 (Ki = 18 nM) sites. 1-NP produces stimulus effects similar to those of TFMPP and is able to antagonize the stimulus effects produced by DOM.The present results suggest that the unsubstituted benzene ring of quipazine, and of its 1-deaza analogue 2-naphthylpiperazine, makes a significant contribution to the binding of these agents to 5-HT2 sites and, more importantly, may account for their 5-HT2 agonist properties.
