2-(4-(8-(thiophen-3-yl)-1H-imidazo[4,5-c][1,7]-naphthyridin-1-yl)phenyl)acetonitrile

ID: ALA3937721

PubChem CID: 134148617

Max Phase: Preclinical

Molecular Formula: C21H13N5S

Molecular Weight: 367.44

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  N#CCc1ccc(-n2cnc3cnc4cnc(-c5ccsc5)cc4c32)cc1

Standard InChI:  InChI=1S/C21H13N5S/c22-7-5-14-1-3-16(4-2-14)26-13-25-20-11-24-19-10-23-18(9-17(19)21(20)26)15-6-8-27-12-15/h1-4,6,8-13H,5H2

Standard InChI Key:  ZZNXKYLUGWNRGG-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 27 31  0  0  0  0  0  0  0  0999 V2000
   15.0506   -2.1048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7557   -1.6960    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.4643   -2.1012    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4651   -2.9203    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.1736   -3.3273    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8819   -2.9165    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8771   -2.0944    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.1680   -1.6910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7575   -3.3334    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0481   -2.9212    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4368   -3.4685    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.7685   -4.2190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5847   -4.1354    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.1285   -4.7416    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8723   -5.5188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4167   -6.1272    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2174   -5.9597    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4709   -5.1783    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9248   -4.5732    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7634   -6.5677    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5099   -7.3445    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2569   -8.1197    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.5913   -3.3245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.6799   -4.1369    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4799   -4.3037    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8858   -3.5943    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   19.3365   -2.9893    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1 10  2  0
  9  4  2  0
  3  2  2  0
  2  1  1  0
  3  4  1  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  2  0
  8  3  1  0
  9 10  1  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13  9  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 14  1  0
 13 14  1  0
 17 20  1  0
 20 21  1  0
 21 22  3  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 27  1  0
 27 23  2  0
  6 23  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3937721

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 367.44

Molecular Weight (Monoisotopic): 367.0892

AlogP: 4.76

#Rotatable Bonds: 3

Polar Surface Area: 67.39

Molecular Species: NEUTRAL

HBA: 6

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.87

CX Basic pKa: 2.58

CX LogP: 3.59

CX LogD: 3.59

Aromatic Rings: 5

Heavy Atoms: 27

QED Weighted: 0.46

Np Likeness Score: -1.62

References

1. Glatthar R, Stojanovic A, Troxler T, Mattes H, Möbitz H, Beerli R, Blanz J, Gassmann E, Drückes P, Fendrich G, Gutmann S, Martiny-Baron G, Spence F, Hornfeld J, Peel JE, Sparrer H..  (2016)  Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors.,  59  (16): [PMID:27502541] [10.1021/acs.jmedchem.6b00598]

2. Gavrin, Lori Krim LK and 14 more authors.  2005-12-01  Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships.  [PMID:16165349]

3. Hu, Yonghan Y and 13 more authors.  2006-12-01  Inhibition of Tpl2 kinase and TNFalpha production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis.  [PMID:16973359]

4. Green, Neal N and 20 more authors.  2007-09-20  Inhibitors of tumor progression loci-2 (Tpl2) kinase and tumor necrosis factor alpha (TNF-alpha) production: selectivity and in vivo antiinflammatory activity of novel 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles.  [PMID:17715908]

5. Hall, J Perry JP and 13 more authors.  2007-11-16  Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood.  [PMID:17848581]

6. Cusack, Kevin K and 19 more authors.  2009-03-15  Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-alpha production.  [PMID:19217782]

7. Glatthar, Ralf and 15 more authors.  2016-08-25  Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors.  [PMID:27502541]

Source

Source(1):

• Scientific Literature