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

ID: ALA4757462

PubChem CID: 162656425

Max Phase: Preclinical

Molecular Formula: C18H17Cl2N3O4S

Molecular Weight: 442.32

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(C)S(=O)(=O)c1c(Cl)ccc(NC2=NC(=O)C(c3ccc(Cl)cc3)N2)c1O

Standard InChI:  InChI=1S/C18H17Cl2N3O4S/c1-9(2)28(26,27)16-12(20)7-8-13(15(16)24)21-18-22-14(17(25)23-18)10-3-5-11(19)6-4-10/h3-9,14,24H,1-2H3,(H2,21,22,23,25)

Standard InChI Key:  VGDCZUAPSONWSZ-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 28 30  0  0  0  0  0  0  0  0999 V2000
    1.3697  -12.9730    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    0.9598  -12.2558    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.5456  -12.9694    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.0818  -11.7329    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0807  -12.5603    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7955  -12.9731    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5119  -12.5598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5090  -11.7293    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7937  -11.3202    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3656  -11.3257    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.3648  -13.7955    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6479  -14.2036    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0768  -14.2122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7932  -13.7964    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2274  -12.9734    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.9420  -12.5612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6988  -12.8996    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2511  -12.2868    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8389  -11.5721    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0319  -11.7434    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.1769  -10.8146    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.0715  -12.3734    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4025  -13.1269    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2222  -13.2139    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7083  -12.5463    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3690  -11.7896    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5503  -11.7063    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5304  -12.6366    0.0000 Cl  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
 11 13  1  0
  6 14  1  0
  7 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 16  2  0
 19 21  2  0
 18 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 22  1  0
 25 28  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4757462

   ---

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: 442.32

Molecular Weight (Monoisotopic): 441.0317

AlogP: 3.52

#Rotatable Bonds: 4

Polar Surface Area: 107.86

Molecular Species: ACID

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 6.30

CX Basic pKa: 3.48

CX LogP: 3.87

CX LogD: 2.79

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.63

Np Likeness Score: -0.89

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