23 research outputs found
Palladium-Catalyzed Cyclocarbonylation of Pyridinylated Vinylogous Amides and Ureas to Generate Ring-Fused Pyridopyrimidinones
As part of a program aimed at generating
new heterocyclic frameworks
for medicinal chemistry exploration, an efficient approach to the
assembly of novel ring-fused pyridopyrimidinones was undertaken. Specifically,
a collection of 11<i>H</i>-pyridoÂ[2,1-<i>b</i>]Âquinazoline-1,11Â(2<i>H</i>)-diones and 2,3-dihydropyridoÂ[1,2-<i>a</i>]ÂpyrroloÂ[3,4-<i>d</i>]Âpyrimidine-1,10-diones
was generated via a palladium-catalyzed, pyridine-directed, cyclocarbonylation
of 2-pyridyl-linked vinylogous amides and ureas in yields of up to
90%
Supplementary Information from Degree heterogeneity and stability of ecological networks
Technical details in obtaining the key results presented in the main text
Refine and Strengthen SAR-Based Read-Across by Considering Bioactivation and Modes of Action
Structure–activity relationship (SAR)-based read-across
is an important and effective method to establish the safety of a
data-poor target chemical (structure of interest (SOI)) using hazard
data from structurally similar source chemicals (analogues). Many
methods use quantitative similarity scores to evaluate the structural
similarity for searching and selecting analogues as well as for evaluating
analogue suitability. However, studies suggest that read-across based
purely on structural similarity cannot accurately predict the toxicity
of an SOI. As mechanistic data become available, we gain a greater
understanding of the mode of action (MOA), the relationship between
structures and metabolism/bioactivation pathways, and the existence
of “activity cliffs” in chemical chain length, which
can improve the analogue rating process. For this purpose, the current
work identifies a series of classes of chemicals where a small change
at a key position can result in a significant change in metabolism
and bioactivation pathways and may eventually result in significant
changes in chemical toxicity that have a big impact on the suitability
of analogues for read-across. Additionally, a series of SAR-based
read-across case studies are presented, which cover a variety of chemical
classes that commonly link to different toxic endpoints. The case
study results indicate that SAR-based read-across can be refined and
strengthened by considering MOAs or proposed reactive metabolite formation
pathways, which can improve the overall accuracy, consistency, transparency,
and confidence in evaluating analogue suitability
Refine and Strengthen SAR-Based Read-Across by Considering Bioactivation and Modes of Action
Structure–activity relationship (SAR)-based read-across
is an important and effective method to establish the safety of a
data-poor target chemical (structure of interest (SOI)) using hazard
data from structurally similar source chemicals (analogues). Many
methods use quantitative similarity scores to evaluate the structural
similarity for searching and selecting analogues as well as for evaluating
analogue suitability. However, studies suggest that read-across based
purely on structural similarity cannot accurately predict the toxicity
of an SOI. As mechanistic data become available, we gain a greater
understanding of the mode of action (MOA), the relationship between
structures and metabolism/bioactivation pathways, and the existence
of “activity cliffs” in chemical chain length, which
can improve the analogue rating process. For this purpose, the current
work identifies a series of classes of chemicals where a small change
at a key position can result in a significant change in metabolism
and bioactivation pathways and may eventually result in significant
changes in chemical toxicity that have a big impact on the suitability
of analogues for read-across. Additionally, a series of SAR-based
read-across case studies are presented, which cover a variety of chemical
classes that commonly link to different toxic endpoints. The case
study results indicate that SAR-based read-across can be refined and
strengthened by considering MOAs or proposed reactive metabolite formation
pathways, which can improve the overall accuracy, consistency, transparency,
and confidence in evaluating analogue suitability
Mock-ablation (PDB) sample video
Processed video showing mock-ablated animal (with segmentation) freely-moving on a bacterial lawn for 15 minutes
PDB ablations_1 feature files and segmented movies
Processed videos of mock- and PDB-ablated animals (with segmentation) freely-moving on a bacterial lawn for 15 minutes, and Matlab files containing data for features extracted from these videos, for replicate 1 of the PDB-ablation experiment
DD5-ablation sample video
Processed video showing DD5-ablated animal (with segmentation) freely-moving on a bacterial lawn for 15 minutes
Synthesis and Biological Activity Evaluation of Novel α‑Amino Phosphonate Derivatives Containing a Pyrimidinyl Moiety as Potential Herbicidal Agents
To
find novel high-activity and low-toxicity herbicide lead compounds
with novel herbicidal mode of action, series of novel α-amino
phosphonate derivatives containing a pyrimidinyl moiety, <b>I</b>, <b>II</b>, <b>III</b>, and <b>IV</b>, were designed
and synthesized by Lewis acid (magnesium perchlorate) catalyzed Mannich-type
reaction of aldehydes, amines, and phosphites. Their structures were
clearly identified by spectroscopy data (IR, <sup>1</sup>H NMR, <sup>31</sup>P NMR, EI-MS) and elemental analyses. The bioassay [in vitro,
in vivo (GH1 and GH2)] showed that most compounds <b>I</b> exhibited
good herbicidal activities; for example, the activities of compounds <b>Ib</b>, <b>Ic</b>, <b>Ig</b>, <b>Ii</b>, <b>Ik</b>, and <b>Im</b> were as good as the positive control
herbicides (acetochlor, atrazine, mesotrione, and glyphosate). However,
their structural isomers <b>II</b> and <b>III</b> and
analogues <b>IV</b> did not display any herbicidal activities
in vivo, although some of them possessed selective inhibitory activity
against Arabidopsis thaliana in vitro.
Interestingly, it was found that compounds <b>IVs</b>, <b>IVt</b>, and <b>IVl</b> showed selective insecticidal activities
against Aphis species or Plutella xylostella, respectively. Their preliminary
herbicidal mode of action and structure–activity relationships
were also studied
DD3 DD4 ablations raw videos (mock/DD3/DD4)
Raw videos of mock-, DD3- and DD4-ablated animals freely-moving on a bacterial lawn for 15 minutes, for the DD3/DD4-ablation experiment
PDB-ablation sample video 1
Processed video showing PDB-ablated animal (with segmentation) freely-moving on a bacterial lawn for 15 minutes