- Design, synthesis, and antitumor activity of novel sorafenib derivatives
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New series of 18 compounds were synthesized using sorafenib derivatives as parent structure and p-aminoacetophenone as raw materials. The structures of the newly synthesized compounds were confirmed on the basis of 1H, 13C NMR and HR
- Chen, Dan-Ping,Fan, Si-Li,Hou, Mi,Li, Xiao-Qin,Li, Zhu-Rui,Ouyang, Gui-Ping,Shao, Li-Hui,Wang, Zhen-Chao,Zou, Ya-Yu
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- Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus
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Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78–22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization.
- Ruan, Banfeng,Zhang, Yuezhou,Tadesse, Solomon,Preston, Sarah,Taki, Aya C.,Jabbar, Abdul,Hofmann, Andreas,Jiao, Yaqing,Garcia-Bustos, Jose,Harjani, Jitendra,Le, Thuy Giang,Varghese, Swapna,Teguh, Silvia,Xie, Yiyue,Odiba, Jephthah,Hu, Min,Gasser, Robin B.,Baell, Jonathan
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supporting information
(2020/02/04)
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- Synthesis and nematicidal activity of piperazinedione derivatives based on the natural product Barettin
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Nematodes are serious constraints of crop production worldwide. However, the traditional nematicides suffer from the side-effects, including environmental and human toxicity. Herein, more than 70 novel piperazinedione derivatives based on the natural product Barettin were synthesized and evaluated against the root-knot nematode Meloidogyne incognita (M. incognita). While most of synthesized compounds exhibited certain nematicidal activity at high concentration, the best one showed a nematicidal activity of 75% at 2.4 μmol/L.
- Sun, Haiyang,Li, Hui,Wang, Jiayi,Song, Gonghua
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p. 977 - 980
(2017/11/16)
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- Efficient Benzimidazolidinone Synthesis via Rhodium-Catalyzed Double-Decarbonylative C-C Activation/Cycloaddition between Isatins and Isocyanates
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The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins) with isocyanates is reported. Initiated by C-C activation, this distinct [5 - 2 + 2] transformation provides a rapid entry to access various benzimidazolidinone derivatives, and a wide range of isocyanates can be efficiently coupled with broad functional group tolerance. A modified one-pot process combining a Curtius rearrangement and C-C activation was also achieved by using acyl azides as the starting materials. A detailed mechanistic study revealed a surprising double-decarbonylative reaction pathway. The novel reactivity discovered in this basic research is expected to shed light on the development of new heterocycle formation methods through C-C/isocyanate coupling.
- Zeng, Rong,Chen, Peng-Hao,Dong, Guangbin
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p. 969 - 973
(2016/02/18)
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- Palladium-catalyzed synthesis of N-aryl carbamates
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An efficient synthesis of aryl carbamates was achieved by introducing alcohols into the reaction of palladium-catalyzed cross-coupling of ArX (X = Cl, OTf) with sodium cyanate. The use of aryl triflates as electrophilic components in this transformation a
- Vinogradova, Ekaterina V.,Park, Nathaniel H.,Fors, Brett P.,Buchwald, Stephen L.
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supporting information
p. 1394 - 1397
(2013/04/24)
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- Matrix isolation, time-resolved IR, and computational study of the photochemistry of benzoyl azide
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It was shown recently on the basis of DFT calculations (N. P. Gritsan and E. A. Pritchina, Mendeleev Commun., 2001, 11, 94) that the singlet states of aroylnitrenes undergo tremendous stabilization due to an extra N-O bonding interaction. To test experimentally the multiplicity and the structure of the lowest state of benzoylnitrenes we performed a study of their photochemistry in Ar matrices at 12 K. Formation of two species was observed on irradiation of benzoyl azide (1b) and its 4-acetyl derivative (1c). One of these species has an IR spectrum, which is consistent with that of isocyanate (2b,c). The IR and UV spectra of the second intermediate are in very good agreement with the calculated spectra of the singlet species (3b,c), whose structure is intermediate between that of a carbonylnitrene and an oxazirene. We further examined the photochemistry of benzoyl azide in solution at ambient temperatures by nanosecond time-resolved IR methods and obtained additional evidence for the singlet ground state of benzoylnitrene as well as insight into its reactivity in acetonitrile, cyclohexane, and dichloromethane. The above experiments were accompanied by quantum chemical calculations which included also a thorough investigation of the parent species, formylnitrene, at different levels of theory.
- Pritchina, Elena A.,Gritsan, Nina P.,Maltsev, Alexander,Bally, Thomas,Autrey, Tom,Liu, Yonglin,Wang, Yuhong,Toscano, John P.
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p. 1010 - 1018
(2007/10/03)
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- Substituted N-phenylcarbamates as histamine H3 receptor antagonists with improved in vivo potency
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Novel substituted N-phenylcarbamates as derivatives of 3-(1 H-imidazol- 4-yl)propanol were prepared and tested for their antagonist potency in vitro and in vivo at histamine H3 receptors. Structural modifications with different alkyl and acetyl moieties were performed in an attempt to optimize pharmacodynamic and pharmacokinetic effects. Most compounds are active in a functional test for histamine H3 receptors on rat cerebral cortex synaptosomes as well as in a peripheral model on guinea pig ileum. But only carbamates without too bulky lipophilic residues showed pronounced to high antagonist potency on the enhancement of endogenous histamine in brain after p.o. administration to mice (ED50 values of 5.5 to 0.86 mg · kg-1). The tested compounds presented weak activities at histamine H1, H2, and muscarinic M3 receptors thus demonstrating their H3-receptor selectivity.
- Reidemeister,Stark, Holger,Ligneau,Ganellin,Schwartz,Schunack
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