Synthesis, Herbicidal Activity, and QSAR of Novel N-Benzothiazolyl- pyrimidine-2,4-diones as Protoporphyrinogen Oxidase Inhibitors

Abstract

Protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4) is known as a key action target for several structurally diverse herbicides. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel 3-(2'-halo-5'-substituted-benzothiazol-1'-yl)-1-methyl-6-(trifluoromethyl)pyrimidine-2,4-diones 9 were designed and synthesized. The bioassay results indicated that a number of the newly synthesized compounds exhibited higher inhibition activity against tobacco PPO (mtPPO) than the controls, saflufenacil and sulfentrazone. Compound 9F-5 was identified as the most potent inhibitor with a Ki value of 0.0072 μM against mtPPO, showing about 4.2-fold and 1.4-fold higher potency than sulfentrazone (Ki = 0.03 μM) and saflufenacil (Ki = 0.01 μM), respectively. An additional green house assay demonstrated that compound 9F-6 (Ki = 0.012 μM) displayed the most promising postemergence herbicidal activity with a broad spectrum even at a concentration as low as 37.5 g of active ingredient (ai)/ha. Maize exhibits relative tolerance against compound 9F-6 at the dosage of 150 g ai/ha, but it is susceptible to saflufenacil even at 75 g ai/ha. Thus, compound 9F-6 exhibits the potential to be a new herbicide for weed control in maize fields.

New and convergent synthesis of saflufenacil

“…Compound 17 was treated with methyl chloroformate to give compound 18 in 86% isolated yield with >98% purity (HPLC). Compound 18 was reacted with ethyl 3‐amino‐4,4,4‐trifluorobut‐2‐enoate ( 2 ) to form the uracil ring to give compound 19 in 78% isolated yield with >99% purity (HPLC) . At the last step, compound 19 was methylated in a two‐phase reaction system to give the final product saflufenacil ( 1 ) in around 86% yield and 98.7% purity (HPLC).…”

Discovery of 2‐(3,4‐dialkoxyphenyl)‐2‐(substituted pyridazin‐3‐yl)acetonitriles as phosphodiesterase 4 inhibitors with anti‐neuroinflammation potential based on three‐dimensional quantitative structure–activity relationship study

“…Based on molecule superimposition or protein crystallography, 3D-QSAR has evolved as a powerful tool in-depth analysis on the correlation between activities and interaction fields, and has been widely used in ligand-based drug design strategies (Beca et al, 2011;Chen, Zhu, Jiang, Liu, & Yang, 2008;Li, Zhang, Li, Zhang, & Chen, 2011;Sashidhara et al, 2015;Yang, Liu, & Yang, 1999;Zuo et al, 2016). Despite numerous 3D-QSAR studies on PDE4 inhibitors with deferent structure types having been published (Gratteri, Bonaccini The actual IC 50 against human PDE4 catalytic domains (PDE4CAT) were obtained from our reported references (Zhou et al, 2015 Marella et al, 2013;Xiong, Lu, Li, Yang, & Zhan, 2006;Zheng et al, 2008), the application of 3D-QSAR study in the design and development of new PDE4 inhibitors is still scarce.…”

Quantitative Structure-Activity Analysis of Triazines Immune Recognition Based on Immunoassay Data for Polyclonal and Monoclonal Antibodies

“…Quantitative structure-activity relationship (QSAR) is widely used studying the immune recognition of diffferent classes of toxic food contaminants, veterinary drugs, including pesticides, etc [11][12][13][14]. The work by Yuan and co-authors reported about an immunoassay analysis of triazines, yet on a small set of 11 compounds [9].…”