compound 11r [PMID: 32045235]   Click here for help

GtoPdb Ligand ID: 10705

Synonyms: Cinnamoyl-cyclopropylalanine-GlnLactam-CO-CO-NH-benzyl
Compound class: Synthetic organic
Comment: Compound 11r is a peptidomimetic α-ketoamide that was designed for antiviral activity against corona- and enteroviruses [2]. This study was posted to the BioRxiv preprint server [1] prior to certification by peer review and publication in J. Med. Chem. The proteases that are essential for viral polyprotein processing by the corona- and enteroviruses exhibit a strong preference for substrates containing Gln at P1 position, and share an active-site conformation that engages the substrate's P1 residue. Compound 11r targets this unique P1-binding position within the active-sites of the main coronavirus protease and the enterovirus 3C protease.
A crystal structure of 11r bound to the human SARS-CoV main protease has been submitted to the RSCB Protein Data Bank with accession ID 5N5O. UniProt P0C6X7 provides details of SARS-CoV proteins.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 4
Rotatable bonds 16
Topological polar surface area 133.47
Molecular weight 572.3
XLogP 4.54
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=C(N[C@H](C(=O)N[C@H](C(=O)C(=O)NCc1ccccc1)C[C@@H]1CCNC1=O)CC1CCCCC1)/C=C/c1ccccc1
Isomeric SMILES O=C(N[C@H](C(=O)N[C@H](C(=O)C(=O)NCc1ccccc1)C[C@@H]1CCNC1=O)CC1CCCCC1)/C=C/c1ccccc1
InChI InChI=1S/C33H40N4O5/c38-29(17-16-23-10-4-1-5-11-23)36-28(20-24-12-6-2-7-13-24)32(41)37-27(21-26-18-19-34-31(26)40)30(39)33(42)35-22-25-14-8-3-9-15-25/h1,3-5,8-11,14-17,24,26-28H,2,6-7,12-13,18-22H2,(H,34,40)(H,35,42)(H,36,38)(H,37,41)/b17-16+/t26-,27-,28-/m0/s1
InChI Key QTGORSKTHIBLJT-FIVJMQNTSA-N
References
1. Zhang L, Lin D, Kusov Y, Nian Y, Ma Q, Wang J, von Brunn A, Leyssen P, Lanko K, Neyts J et al.. (2020)
Alpha-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication.
bioRxiv,. DOI: 10.1101/2020.02.10.936898
2. Zhang L, Lin D, Kusov Y, Nian Y, Ma Q, Wang J, von Brunn A, Leyssen P, Lanko K, Neyts J et al.. (2020)
α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment.
J Med Chem, 63 (9): 4562-4578. [PMID:32045235]
3. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, Backer S, Rox K, Hilgenfeld R. (2020)
Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors.
Science,. DOI: 10.1126/science.abb3405