183945-55-3Relevant academic research and scientific papers
Cyclopropyl alkenyl amide derivative and synthesizing method thereof
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Paragraph 0080; 0081; 0082; 0084, (2017/07/19)
The invention discloses a cyclopropyl alkenyl amide derivative and a synthesizing method thereof. The method is characterized in that 1,1-dialkyl sulphanyl-1-alkenyl-3-cyclopropanone is utilized to synthesize 1-alkyl sulphanyl-1-amido-1-alkenyl-3-cyclopropanone, and then 1-alkyl sulphanyl-1-amido-1-alkenyl-3-cyclopropanone further reacts with iodosobenzene diacetate; 3-acetate, 1,3-carbonyl migration and 2,3-alkyl sulphanyl migration reaction are carried out to generate the cyclopropyl alkenyl amide derivative which can be further transformed to generate a functional product. The method has the advantages that the raw materials are easy to obtain; the operation is simple and convenient; the synthesizing reaction is mild in conditions; the efficiency is high; the substrate adaption is high; the product stereoselectivity is high; the functional group has diversity.
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.
