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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2D Structure
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Physico-chemical Properties
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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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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]