Ethyl-2-(3-(3,4-dimethoxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate

ID: ALA4779885

PubChem CID: 162662835

Max Phase: Preclinical

Molecular Formula: C21H26N2O4S2

Molecular Weight: 434.58

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCOC(=O)c1c(NC(=S)Nc2ccc(OC)c(OC)c2)sc2c1C(C)CCC2

Standard InChI:  InChI=1S/C21H26N2O4S2/c1-5-27-20(24)18-17-12(2)7-6-8-16(17)29-19(18)23-21(28)22-13-9-10-14(25-3)15(11-13)26-4/h9-12H,5-8H2,1-4H3,(H2,22,23,28)

Standard InChI Key:  CGBSCEYRGGKKMU-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 29 31  0  0  0  0  0  0  0  0999 V2000
   27.7792   -8.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.7792   -8.8792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.4913   -9.2875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.4913   -7.6375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2033   -8.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2033   -8.8802    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9889   -9.1356    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   30.4745   -8.4673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9890   -7.7991    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.4913   -6.8125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.2439   -7.0144    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.0509   -6.8429    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   29.6919   -6.4013    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   31.3058   -6.0583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.1128   -5.8868    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.2995   -8.4673    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.7120   -9.1817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.5370   -9.1817    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.2995   -9.8962    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   32.9495   -8.4673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.7750   -8.4694    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.1874   -7.7558    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.5369   -7.7573    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.9456   -7.0430    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.7705   -7.0373    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.0155   -7.7579    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.1803   -6.3209    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   35.0053   -6.3174    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.4297   -7.0444    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  4  1  0
  2  3  1  0
  3  6  1  0
  5  4  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  8  9  2  0
  9  5  1  0
  4 10  1  0
  9 11  1  0
 11 12  1  0
 11 13  2  0
 12 14  1  0
 14 15  1  0
  8 16  1  0
 16 17  1  0
 17 18  1  0
 17 19  2  0
 18 20  1  0
 20 21  2  0
 21 22  1  0
 22 25  2  0
 24 23  2  0
 23 20  1  0
 24 25  1  0
 22 26  1  0
 25 27  1  0
 27 28  1  0
 26 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4779885

   ---

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: 434.58

Molecular Weight (Monoisotopic): 434.1334

AlogP: 5.19

#Rotatable Bonds: 6

Polar Surface Area: 68.82

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.49

CX Basic pKa: ┄

CX LogP: 6.52

CX LogD: 6.52

Aromatic Rings: 2

Heavy Atoms: 29

QED Weighted: 0.48

Np Likeness Score: -1.27

References

1. Xue D,Chen W,Neamati N.  (2020)  Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists.,  204  [PMID:32829163] [10.1016/j.ejmech.2020.112387]

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