7285-66-7Relevant academic research and scientific papers
Synthesis and antiprotozoal activity of dicationic m-terphenyl and 1,3-dipyridylbenzene derivatives
Patrick, Donald A.,Ismail, Mohamed A.,Arafa, Reem K.,Wenzler, Tanja,Zhu, Xiaohua,Pandharkar, Trupti,Jones, Susan Kilgore,Werbovetz, Karl A.,Brun, Reto,Boykin, David W.,Tidwell, Richard R.
, p. 5473 - 5494 (2013/07/26)
4,4″-Diamidino-m-terphenyl (1) and 36 analogues were prepared and assayed in vitro against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Plasmodium falciparum, and Leishmania amazonensis. Twenty-three compounds were highly active against T. b. rhodesiense or P. falciparum. Most noteworthy were amidines 1, 10, and 11 with IC50 of 4 nM against T. b. rhodesiense, and dimethyltetrahydropyrimidinyl analogues 4 and 9 with IC50 values of ≤ 3 nM against P. falciparum. Bis-pyridylimidamide derivative 31 was 25 times more potent than benznidazole against T. cruzi and slightly more potent than amphotericin B against L. amazonensis. Terphenyldiamidine 1 and dipyridylbenzene analogues 23 and 25 each cured 4/4 mice infected with T. b. rhodesiense STIB900 with four daily 5 mg/kg intraperitoneal doses, as well as with single doses of ≤10 mg/kg. Derivatives 5 and 28 (prodrugs of 1 and 25) each cured 3/4 mice with four daily 25 mg/kg oral doses.
Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases
Davies, Matthew,Heikkil?, Timo,McConkey, Glenn A.,Fishwick, Colin W. G.,Parsons, Mark R.,Johnson, A. Peter
supporting information; experimental part, p. 2683 - 2693 (2010/01/16)
Pyrimidine biosynthesis is an attractive drug target in a variety of organisms, including humans and the malaria parasite Plasmodium falciparum. Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. In this study, we have applied SPROUT-LeadOpt, a software package for structure-based drug discovery and lead optimization, to improve the binding of the active metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum and human dihydroorotate dehydrogenases. Following synthesis of a library of compounds based upon the SPROUT-optimized molecular scaffolds, a series of inhibitors generally showing good inhibitory activity was obtained, in keeping with the SPROUTLeadOpt predictions. Furthermore, cocrystal structures of five of these SPROUT-designed inhibitors bound in the ubiquinone binding cavity of the human dihydroorotate dehydrogenase are also analyzed.
Photolysis of Tetraarylmethanes and 3-(Triarylmethyl)pyridines
Shi, Min,Okamoto, Yoshiki,Takamuku, Setsuo
, p. 2731 - 2733 (2007/10/02)
Upon UV irradiation in benzene-methanol (1:2) tetraarylmethanes or 3-(triarylmethyl)pyridines underwent an α,α-elimination of two aryl groups to give biaryls or 3-arylpyridine, and two corresponding carbene intermediates.The latters afforded methyl ethers by O-H insertion to methanol.
