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

ID: ALA4780042

PubChem CID: 162663287

Max Phase: Preclinical

Molecular Formula: C21H27N3O2S2

Molecular Weight: 417.60

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCOC(=O)c1c(NC(=S)Nc2ccc(N(C)C)cc2)sc2c1C(C)CCC2

Standard InChI:  InChI=1S/C21H27N3O2S2/c1-5-26-20(25)18-17-13(2)7-6-8-16(17)28-19(18)23-21(27)22-14-9-11-15(12-10-14)24(3)4/h9-13H,5-8H2,1-4H3,(H2,22,23,27)

Standard InChI Key:  BCOMNVLIXFHAHF-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

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    0.5541   -8.5791    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5541   -9.4041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2662   -9.8124    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2662   -8.1624    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9782   -8.5791    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9781   -9.4051    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7637   -9.6604    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    3.2493   -8.9921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7638   -8.3239    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2662   -7.3374    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0187   -7.5393    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8257   -7.3679    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.4667   -6.9262    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.0807   -6.5832    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8876   -6.4117    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0743   -8.9921    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.4868   -9.7066    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3118   -9.7066    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.0743  -10.4210    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    5.7243   -8.9921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5498   -8.9943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9622   -8.2807    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5497   -7.5652    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.7204   -7.5679    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3117   -8.2821    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9639   -6.8491    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.5520   -6.1343    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7608   -6.6356    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 23  2  0
 23 24  1  0
 24 25  2  0
 25 20  1  0
 23 26  1  0
 26 27  1  0
 26 28  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4780042

   ---

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: 417.60

Molecular Weight (Monoisotopic): 417.1545

AlogP: 5.24

#Rotatable Bonds: 5

Polar Surface Area: 53.60

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.55

CX Basic pKa: 4.74

CX LogP: 6.95

CX LogD: 6.94

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.51

Np Likeness Score: -1.53

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