Table 4SAR Analysis for NOD1-Selective Benzimidazole Scaffold

SAR Analysis for NOD1 Selective Scaffolds (Medicinal Chemistry & Cheminformatics Analysis)
Image ml130fu5.jpg
Potency (µM) mean ± S.E.M. (n = replicates)NOD1 to NOD2-fold sel.
#CIDSIDBCCG MLS-*R1R2R3XYnNOD1NOD2
11088438
Probe
ML130
852483600350096PHHMeNH270.56 ±0.04>20>36
85176678SSO260.71 ±0.15>20>28
21088439852562320425609PHHClSO2NH220.48±0.14>20>41
85248349S20.093 ±0.0119.9 ±0.15210
344229066852483620425616SHHOMeSO2NH242.7 ±0.69>20>7.5
43025920852483610425615SHHHSO2NH242.2 ±0.21>20>9.0
53025945852483630425617SHHNO2SO2NH2614 ±1.8>20>1.4
6746711852483450082307PHHMeSO2H26.3 ±0.81>20>3.2
7755364852855760350366PHHMeSO2Me2>20>20-
82796863852483520425611PMeHMeSO2SH2>20>20-
944229067852483640425618SMeMeMeSO2NH24>20>20-
10743900852856400425658PHHClCH2NH227.7±0.8211.9±0.51.5
111088435852483500425610PHH2,4-diClCONH222.8±0.573.8±1.51.3
121088431852855780281258PHHFCONH2218±2.0>20-
13761923852856360350139PHHClCH2CH2ONH2216.3 ±3.7>20-
14584781852856000425671PHHOMeCH2CONH22>20>20-
151088429852855770425645PHHHCOCH2NH22>20>20-
*

S = Synthesized P = purchased

All structures were inactive in a cytoxicity assay (0% activity @ 20 µM)

All structures except compound 11 [SID-85248350 (3.2 µM)] were inactive in the TNFα assay (0% activity @ 20 µM)

From: High Throughput Screening Assays for NOD1 Inhibitors - Probe 1

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Probe Reports from the NIH Molecular Libraries Program [Internet].

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