3-chloro-2-(isopropylsulfonyl)-6-(5-phenyl-4H-1,2,4-triazol-3-ylamino)phenol

ID: ALA4536494

PubChem CID: 151755055

Max Phase: Preclinical

Molecular Formula: C17H17ClN4O3S

Molecular Weight: 392.87

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(C)S(=O)(=O)c1c(Cl)ccc(Nc2nnc(-c3ccccc3)[nH]2)c1O

Standard InChI:  InChI=1S/C17H17ClN4O3S/c1-10(2)26(24,25)15-12(18)8-9-13(14(15)23)19-17-20-16(21-22-17)11-6-4-3-5-7-11/h3-10,23H,1-2H3,(H2,19,20,21,22)

Standard InChI Key:  RPIZWOPUYCDULD-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 26 28  0  0  0  0  0  0  0  0999 V2000
   26.2904   -4.3955    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.9534   -3.9176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.6990   -3.1326    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.8777   -3.1326    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.6234   -3.9176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6607   -4.3253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6564   -5.1433    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3628   -5.5552    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.0726   -5.1459    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.0716   -4.3248    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3646   -3.9207    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2387   -4.3212    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.0600   -4.3253    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   21.6550   -3.6114    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.7768   -3.0954    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7756   -3.9190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.4878   -4.3280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.2016   -3.9186    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.1987   -3.0918    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.4860   -2.6824    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.0648   -2.6828    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   23.4876   -5.1493    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.0628   -5.1484    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.3548   -5.5606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7743   -5.5617    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.9140   -4.3261    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  4  5  2  0
  2  3  2  0
  1  2  1  0
  3  4  1  0
  5  1  1  0
  2  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11  6  1  0
 13 12  2  0
 14 13  2  0
 15 16  2  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 15  1  0
 15 21  1  0
 17 22  1  0
 16 13  1  0
 13 23  1  0
 23 24  1  0
 23 25  1  0
 18 26  1  0
 26  5  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4536494

   ---

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: 392.87

Molecular Weight (Monoisotopic): 392.0710

AlogP: 3.76

#Rotatable Bonds: 5

Polar Surface Area: 107.97

Molecular Species: ACID

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 6.24

CX Basic pKa: 2.69

CX LogP: 3.91

CX LogD: 2.77

Aromatic Rings: 3

Heavy Atoms: 26

QED Weighted: 0.57

Np Likeness Score: -1.23

References

1. Che J, Song R, Chen B, Dong X..  (2020)  Targeting CXCR1/2: The medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead.,  185  [PMID:31732253] [10.1016/j.ejmech.2019.111853]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

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

9. 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]

10. 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]

11. 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]

12. 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]

13. 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