367488-48-0Relevant academic research and scientific papers
Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues
Zhang, Kai,Li, Jiarong,Liu, Honglin,Wang, Haiyou,Lamusi
, p. 2321 - 2330 (2018/09/14)
Spinetoram, a mixture of spinetoram J (XDE-175-J, major component) and spinetoram L (XDE-175-L), is a new kind of fermentation-derived insecticide with a broad range of action against many insect pests, especially Cydia pomonella, Leaf miner and Thrips. Similar to spinosad, spinetoram is friendly to the environment, and non-toxic to animals and human beings. Therefore, spinetoram has been widely applied in pest control and grain storage. In a previous study, we had reported a semi-synthesis of spinetoram J. However, in that synthesis, there were more experimental steps, and the operations were troublesome. So an improved synthesis based on a self-protection strategy was designed and discussed. In this work, 3-O-ethyl-2,4-di-O-methylrhamnose was used as both the reaction substrate of C9–OH and the protecting group of C17–OH. The number of synthetic steps and costs were significantly reduced. In addition, a variety of D-forosamine replacement analogues of spinetoram J were synthesized based on the improved semi-synthesis, and their insecticidal activities were evaluated against third-instar larvae of Plutella xylostella. Although none of the analogues were as potent as spinetoram, a few of the analogues have only a 20–40 times lower activity than spinetoram. In particular, one of these analogues was approximately as active as spinosad. This study highlights the possibility of developing new insecticidal chemistries by replacing sugars on natural products with other groups, and the improved semi-synthesis will be helpful for further researches on spinetoram.
Synthesis, in vitro pharmacology, structure - Activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6- dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists
Nakazato, Atsuro,Sakagami, Kazunari,Yasuhara, Akito,Ohta, Hiroshi,Yoshikawa, Ryoko,Itoh, Manabu,Nakamura, Masato,Chaki, Shigeyuki
, p. 4570 - 4587 (2007/10/03)
Novel group II metabotropic glutamate receptor (mGluR) antagonists, 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, were discovered by the incorporation of a hydroxy or alkoxyl group onto the C-3 portion of selective and potent group II mGluR agonist 5, (1R,2S,5R,6R)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid. Among these compounds, (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6- fluorobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (-)-11be (MGS0039) was a highly selective and potent group II mGluR antagonist with the best pharmacokinetic profile. Compound (-)-11be exhibited high affinities for mGlu 2 (Ki = 2.38 ± 0.40 nM) and mGlu 3 (4.46 ± 0.31 nM) but low affinity for mGluR 7 (Ki = 664 ± 106 nM), and potent antagonist activities for mGlu 2 (IC50 = 20.0 ± 3.67nM) and mGluR 3 (IC50 = 24.0 ± 3.54 nM) but much less potent antagonist activities for mGlu 4 (IC50 = 1740 ± 1080 nM), mGlu 6 (IC50 = 2060 ± 1270 nM), mGlu 1 (IC50 = 93300 ± 14600 nM), and mGluR 5 (IC50 = 117000 ± 38600 nM). No significant agonist activities of (-)-11be were found for mGluRs 2, 3, 4, 6, 1, and 5 (EC50 > 100000 nM). Furthermore, (-)-11be exhibited dose-dependent oral absorption (plasma Cmax: 214 ± 56.7, 932 ± 235, and 2960 ± 1150 ng/mL for 3 mg/kg, 10 mg/kg, and 30 mg/kg, po, respectively) and acceptable blood-brain barrier penetration (brain C max: 13.2 ng/mL for 10 mg/kg, po 6 h). In this paper, we report the synthesis, in vitro pharmacological profile, and structure-activity relationships (SARs) of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6- dicarboxylic acid derivatives 11 and 12, and pharmacokinetic profiles of several typical compounds.
Design and synthesis of potent C2-symmetric diol-based HIV-1 protease inhibitors: Effects of fluoro substitution
Pyring,Lindberg,Rosenquist,Zuccarello,Kvarnstr?m,Zhang,Vrang,Unge,Classon,Hallberg,Samuelsson
, p. 3083 - 3091 (2007/10/03)
Implementation of derivatized carbohydrates as C2-symmetric HIV-1 protease inhibitors has previously been reported. With the objective of improving the anti-HIV activity of such compounds, we synthesized a series of fluoro substituted P1/P1′ an
