Synthesis of novel indole substituted heterocyclics

51-59Herein is reported the synthesis of a series (21 number) of novel hybrid molecules composed of an indole-3-carbaldehyde attached to triazole/ isoxazole/ isoxazoline moieties having various aromatic/benzylic/aliphatic substitutions via 1,3-dipolar cycloaddition between azide/ nitrile oxide (dipole) and indole substituted alkyne/ alkene (dipolarophile) based on the importance of indole, 1,2,3-triazole, isoxazole and isoxazoline containing pharmacophores

Synthesis of novel indole substituted heterocyclics

Herein is reported the synthesis of a series (21 number) of novel hybrid molecules composed of an indole-3-carbaldehyde attached to triazole/ isoxazole/ isoxazoline moieties having various aromatic/benzylic/aliphatic substitutions via 1,3-dipolar cycloaddition between azide/ nitrile oxide (dipole) and indole substituted alkyne/ alkene (dipolarophile) based on the importance of indole, 1,2,3-triazole, isoxazole and isoxazoline containing pharmacophores

Design, Synthesis, and Herbicidal Activity of Pyrimidine–Biphenyl Hybrids as Novel Acetohydroxyacid Synthase Inhibitors

The issue of weed resistance to acetohydroxyacid synthase (EC 2.2.1.6, AHAS) inhibitors has become one of the largest obstacles for the application of this class of herbicides. In a continuing effort to discover novel AHAS inhibitors to overcome weed resistance, a series of pyrimidine–biphenyl hybrids (<b>4aa</b>–<b>bb</b> and <b>5aa</b>–<b>ah</b>) were designed and synthesized via a scaffold hopping strategy. Among these derivatives, compounds <b>4aa</b> (<i>K</i>_i = 0.09 μM) and <b>4bb</b> (<i>K</i>_i = 0.02 μM) displayed higher inhibitory activities against <i>Arabidopsis thaliana</i> AHAS than those of the controls bispyribac (<i>K</i>_i = 0.54 μM) and flumetsulam (<i>K</i>_i = 0.38 μM). Remarkably, compounds <b>4aa</b>, <b>4bb</b>, <b>5ah</b>, and <b>5ag</b> exhibited excellent postemergence herbicidal activity and a broad spectrum of weed control at application rates of 37.5–150 g of active ingredient (ai)/ha. Furthermore, <b>4aa</b> and <b>4bb</b> showed higher herbicidal activity against AHAS inhibitor-resistant <i>Descurainia sophia</i>, <i>Ammannia arenaria</i>, and the corresponding sensitive weeds than that of bispyribac at 0.94–0.235 g ai/ha. Therefore, the pyrimidine–biphenyl motif and lead compounds <b>4aa</b> and <b>4bb</b> have great potential for the discovery of novel AHAS inhibitors to combat AHAS-inhibiting herbicide-resistant weeds

Discovery of New 2‑[(4,6-Dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted phenoxy)benzoic Acids as Flexible Inhibitors of <i>Arabidopsis thaliana</i> Acetohydroxyacid Synthase and Its P197L Mutant

In the search for new antiresistance acetohydroxyacid synthase (AHAS, EC 2.2.1.6) inhibitors to combat weed resistance associated with AHAS mutations, a series of 2-[(4,6-dimethoxy-1,3,5-triazin-2-yl)­oxy]-6-(substituted phenoxy)­benzoic acids <b>11</b>–<b>38</b> were designed and synthesized via the strategy of conformational flexibility analysis. Compounds <b>21</b>, <b>22</b>, <b>26</b>, <b>33</b>, <b>36</b>, and <b>38</b> with high potency against both wild-type <i>At</i>AHAS and its P197L mutant were identified as promising candidates with low resistance factors (RF, defined as the ratio between the <i>k</i>_i values toward P197L mutant and wild-type AHAS) ranging from 0.73 to 6.32. Especially, compound <b>22</b> (RF = 0.73) was further identified as the most potent antiresistance AHAS inhibitor because of its significantly reduced resistance level compared with that of tribenuron-methyl (RF = 2650) and bispyribac (RF = 4.57). Furthermore, compounds <b>26</b>, <b>33</b>, <b>36</b>, and <b>38</b> also displayed promising herbicidal activities against sensitive and resistant (P197L) Descurainia sophia at the dosage of 75–150 g of active ingredient (ai)/ha. Notably, compounds <b>33</b> and <b>38</b> still maintained over 60% herbicidal activity toward the resistant weed even at much lower dosages (37.5 g ai/ha). Therefore, the designed scaffold has the great potential to discover new candidate compounds for the control of weed resistance associated with AHAS mutation