BI 653048   Click here for help

GtoPdb Ligand ID: 9715

Synonyms: (R)-39 [2] | BI 653048 BS H3PO4 [3] | BI-653048 | BI653048
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BI 653048 is a "dissociated" glucocorticoid receptor (GR) agonist (displaying different transcriptional regulatory profiles between gene transrepression and transactivation). This type of drug is designed to reduce the unwanted side-effects common to traditional GR agonists [1-2]. It has favourable drug-like properties, but because it has reduced mouse functional transrepression potency it is not suitable for evaluation in standard preclinical mouse models. BI 653048 is synthesised as the phosphoric acid (H3PO4) cocrystal to optimise physicochemical properties, stability characteristics, solubility and bioavailability compared to the free form [3].
This ligand is one of the compounds available from Boehringer Ingelheim's opnMe molecular library.
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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 6
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 134.52
Molecular weight 515.15
XLogP 4.32
No. Lipinski's rules broken 0
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 CCS(=O)(=O)c1ncc2c(c1)cc([nH]2)CC(C(F)(F)F)(CC(c1ccc(cc1C(=O)N)F)(C)C)O
Isomeric SMILES CCS(=O)(=O)c1ncc2c(c1)cc([nH]2)C[C@@](C(F)(F)F)(CC(c1ccc(cc1C(=O)N)F)(C)C)O
InChI InChI=1S/C23H25F4N3O4S/c1-4-35(33,34)19-8-13-7-15(30-18(13)11-29-19)10-22(32,23(25,26)27)12-21(2,3)17-6-5-14(24)9-16(17)20(28)31/h5-9,11,30,32H,4,10,12H2,1-3H3,(H2,28,31)/t22-/m0/s1
InChI Key AUIFRJWXYUNPPV-QFIPXVFZSA-N
References
1. Harcken C, Riether D, Kuzmich D, Liu P, Betageri R, Ralph M, Emmanuel M, Reeves JT, Berry A, Souza D et al.. (2014)
Identification of highly efficacious glucocorticoid receptor agonists with a potential for reduced clinical bone side effects.
J Med Chem, 57 (4): 1583-98. [PMID:24506830]
2. Harcken C, Riether D, Liu P, Razavi H, Patel U, Lee T, Bosanac T, Ward Y, Ralph M, Chen Z et al.. (2014)
Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate.
ACS Med Chem Lett, 5 (12): 1318-23. [PMID:25516791]
3. Reeves JT, Fandrick DR, Tan Z, Song JJ, Rodriguez S, Qu B, Kim S, Niemeier O, Li Z, Byrne D et al.. (2013)
Development of a large scale asymmetric synthesis of the glucocorticoid agonist BI 653048 BS H3PO4.
J Org Chem, 78 (8): 3616-35. [PMID:23544738]