2-((4-Chloro-2-hydroxy-3-((2-methoxyethyl)sulfonyl)phenyl)amino)-5-phenyl-1,5-dihydro-4H-imidazol-4-one

ID: ALA4763312

PubChem CID: 162659583

Max Phase: Preclinical

Molecular Formula: C18H18ClN3O5S

Molecular Weight: 423.88

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  COCCS(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccccc3)N2)c1O

Standard InChI:  InChI=1S/C18H18ClN3O5S/c1-27-9-10-28(25,26)16-12(19)7-8-13(15(16)23)20-18-21-14(17(24)22-18)11-5-3-2-4-6-11/h2-8,14,23H,9-10H2,1H3,(H2,20,21,22,24)

Standard InChI Key:  DYFXQMZMYIFFKC-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 28 30  0  0  0  0  0  0  0  0999 V2000
   10.1891   -2.7183    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    9.7830   -2.0078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.3728   -2.7146    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.8945   -1.4899    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8933   -2.3094    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.6014   -2.7184    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3110   -2.3090    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3082   -1.4863    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5996   -1.0810    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1849   -1.0865    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   10.1842   -3.5329    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4740   -3.9372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5991   -3.5338    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.0198   -2.7186    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.7277   -2.3104    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4772   -2.6456    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.0243   -2.0385    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6161   -1.3306    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.8167   -1.5002    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.9509   -0.5803    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.8370   -2.1244    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1650   -2.8708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9769   -2.9569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4584   -2.2955    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.1223   -1.5460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.3113   -1.4636    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4691   -4.7544    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.7590   -5.1588    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  1  3  2  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9  4  1  0
  4 10  1  0
  5  1  1  0
  1 11  1  0
 11 12  1  0
  6 13  1  0
  7 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 15  2  0
 18 20  2  0
 17 21  1  0
 21 22  2  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  2  0
 26 21  1  0
 12 27  1  0
 27 28  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4763312

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 423.88

Molecular Weight (Monoisotopic): 423.0656

AlogP: 2.10

#Rotatable Bonds: 6

Polar Surface Area: 117.09

Molecular Species: ACID

HBA: 7

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 6.31

CX Basic pKa: 3.57

CX LogP: 2.30

CX LogD: 1.21

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.61

Np Likeness Score: -0.88

References

1. Che J,Wang Z,Shen Z,Zhuang W,Ying H,Hu Y,Hu Y,Xie X,Dong X.  (2021)  Discovery of 1,5-Dihydro-4H-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2.,  12  (5.0): [PMID:34055234] [10.1021/acsmedchemlett.1c00113]

2. Cutshall, N S NS, Ursino, R R, Kucera, K A KA, Latham, J J and Ihle, N C NC.  2001-07-23  Nicotinamide N-oxides as CXCR2 antagonists.  [PMID:11459668]

3. Cutshall, Neil S NS, Kucera, Kristin A KA, Ursino, Rocky R, Latham, John J and Ihle, Nathan C NC.  2002-06-03  Nicotinanilides as inhibitors of neutrophil chemotaxis.  [PMID:12031332]

4. Widdowson, Katherine L KL and 14 more authors.  2004-03-11  Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor.  [PMID:14998320]

5. Karlström, Sofia S and 20 more authors.  2013-04-25  Substituted 7-amino-5-thio-thiazolo[4,5-d]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1).  [PMID:23516963]

6. Bachelerie, Francoise F and 22 more authors.  2014  International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors.  [PMID:24218476]

7. Austin, Rupert P RP and 14 more authors.  2015-04-01  Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists.  [PMID:25708618]

8. Maeda, Dean Y and 8 more authors.  2015-06-01  Boronic acid-containing CXCR1/2 antagonists: Optimization of metabolic stability, in vivo evaluation, and a proposed receptor binding model.  [PMID:25933594]

9. Miller, Bruce E and 8 more authors.  2015-06-20  The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects.  [PMID:26092545]

10. Schuler, Aaron D and 8 more authors.  2015-09-15  Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailability.  [PMID:26248802]

11. Xu, Heng H and 19 more authors.  2016-04-14  Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders.  [PMID:27096048]

12. Gege, Christian and 15 more authors.  2018-05-15  Identification and biological evaluation of thiazole-based inverse agonists of RORγt.  [PMID:29631962]

Source

Source(1):

• Scientific Literature