(R)-1-Ethylsulfanyl-6-methyl-4-phenyl-6,7,8,9-tetrahydro-4H-10-thia-2,3,4,10b-tetraaza-cyclopenta[a]fluoren-5-one

ID: ALA4482876

PubChem CID: 990571

Max Phase: Preclinical

Molecular Formula: C20H20N4OS2

Molecular Weight: 396.54

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCSc1nnc2n(-c3ccccc3)c(=O)c3c4c(sc3n12)CCC[C@H]4C

Standard InChI:  InChI=1S/C20H20N4OS2/c1-3-26-20-22-21-19-23(13-9-5-4-6-10-13)17(25)16-15-12(2)8-7-11-14(15)27-18(16)24(19)20/h4-6,9-10,12H,3,7-8,11H2,1-2H3/t12-/m1/s1

Standard InChI Key:  BKCUNJWZPSZRJN-GFCCVEGCSA-N

Molfile:  

 
     RDKit          2D

 27 31  0  0  0  0  0  0  0  0999 V2000
   29.2694   -5.9143    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.5599   -5.5016    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.2694   -6.7356    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.5657   -7.1461    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.7359   -7.9411    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.5448   -8.0236    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   29.8760   -7.2796    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   27.8505   -6.7356    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.8460   -5.9144    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0707   -6.9965    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   26.5867   -6.3340    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0621   -5.6700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.7302   -4.9282    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.9177   -4.8443    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.4381   -5.5083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.7752   -6.2563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9787   -5.5099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.6897   -5.9222    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.4022   -5.5164    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.4050   -4.6942    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.6894   -4.2796    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9798   -4.6919    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.5611   -4.6803    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.2129   -4.2618    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.1906   -8.5539    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   28.4451   -9.3346    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.8957   -9.9433    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  9  2  1  0
  8  4  1  0
  3  1  1  0
  1  2  1  0
  3  4  1  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  7  3  2  0
  8  9  2  0
  9 12  1  0
 11 10  1  0
 10  8  1  0
 11 12  2  0
 11 16  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 17  1  0
  1 17  1  0
  2 23  2  0
 13 24  1  1
  5 25  1  0
 25 26  1  0
 26 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4482876

   (11R)-3-ethylsulfanyl-11-methyl-7-phenyl-16-thia-2,4,5,7-tetrazatetracyclo[7.7.0.02,6.010,15]hexadeca-1(9),3,5,10(15)-tetraen-8-one

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: 396.54

Molecular Weight (Monoisotopic): 396.1079

AlogP: 4.65

#Rotatable Bonds: 3

Polar Surface Area: 52.19

Molecular Species: NEUTRAL

HBA: 7

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 5.48

CX LogD: 5.48

Aromatic Rings: 4

Heavy Atoms: 27

QED Weighted: 0.47

Np Likeness Score: -1.90

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. 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