compound 27 [PMID: 32551645]   Click here for help

GtoPdb Ligand ID: 11112

Compound class: Synthetic organic
Comment: Compound 27 was designed to offer improved clinical potential as a utrophin modulator than either ezutromid (failed at Phase 2) or SMT022357 (terminated at preclinical) [1]. This entry shows the compound without specified stereochemistry, to represent the racemic mixture. (+)-27 is slightly more active than (-)-27 or the racemate in vitro.

Clinical rationale: Up-regulation of utrophin (UTRN; P46939) as being investigated as a disease-modifying approach for Duchenne muscular dystrophy (DMD). In the mdx mouse DMD model, increased levels of utrophin effectively acts as a substitute for the dystrophin (DMD; P11532) that is missing in DMD [2].
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 3
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 62.14
Molecular weight 319.08
XLogP 3.37
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 CCP(=O)(c1ccc2c(c1)nc(o2)c1ccc(cc1)F)OC
Isomeric SMILES CCP(=O)(c1ccc2c(c1)nc(o2)c1ccc(cc1)F)OC
InChI InChI=1S/C16H15FNO3P/c1-3-22(19,20-2)13-8-9-15-14(10-13)18-16(21-15)11-4-6-12(17)7-5-11/h4-10H,3H2,1-2H3
InChI Key MNCZMYLRBLYUPR-UHFFFAOYSA-N
References
1. Babbs A, Berg A, Chatzopoulou M, Davies KE, Davies SG, Edwards B, Elsey DJ, Emer E, Guiraud S, Harriman S et al.. (2020)
2-Arylbenzo[d]oxazole Phosphinate Esters as Second-Generation Modulators of Utrophin for the Treatment of Duchenne Muscular Dystrophy.
J Med Chem, 63 (14): 7880-7891. [PMID:32551645]
2. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, Powell DS, Cozzoli A, Capogrosso RF, Lambert A et al.. (2011)
Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse.
PLoS ONE, 6 (5): e19189. [PMID:21573153]