1-(1H-benzo[d]imidazol-6-yl)-8-(piperidin-1-yl)-1Himidazo[4,5-c][1,7]naphthyridine

ID: ALA3981321

PubChem CID: 134157715

Max Phase: Preclinical

Molecular Formula: C21H19N7

Molecular Weight: 369.43

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  c1nc2ccc(-n3cnc4cnc5cnc(N6CCCCC6)cc5c43)cc2[nH]1

Standard InChI:  InChI=1S/C21H19N7/c1-2-6-27(7-3-1)20-9-15-18(10-23-20)22-11-19-21(15)28(13-26-19)14-4-5-16-17(8-14)25-12-24-16/h4-5,8-13H,1-3,6-7H2,(H,24,25)

Standard InChI Key:  BQNLSAONLCMRGJ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 28 33  0  0  0  0  0  0  0  0999 V2000
   13.5937   -1.6797    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2988   -1.2709    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.0074   -1.6761    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0082   -2.4952    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7167   -2.9022    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4250   -2.4914    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4202   -1.6693    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.7111   -1.2659    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.3006   -2.9082    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5911   -2.4961    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9799   -3.0434    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.3116   -3.7939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1278   -3.7103    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.6716   -4.3165    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4154   -5.0937    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.0140   -4.7532    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4678   -4.1481    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7682   -5.5364    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9589   -5.7049    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8690   -6.5267    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6228   -6.8662    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1785   -6.2541    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.1384   -2.8944    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.1418   -3.7179    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8512   -4.1209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5593   -3.7080    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5536   -2.8877    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8397   -2.4802    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 19  1  0
 18 16  1  0
 16 17  2  0
 17 14  1  0
 13 14  1  0
 18 19  2  0
 19 20  1  0
 20 21  1  0
 21 22  2  0
 22 18  1  0
  6 23  1  0
 23 24  1  0
 23 28  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3981321

   ---

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: 369.43

Molecular Weight (Monoisotopic): 369.1702

AlogP: 3.84

#Rotatable Bonds: 2

Polar Surface Area: 75.52

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.22

CX Basic pKa: 6.32

CX LogP: 2.92

CX LogD: 2.89

Aromatic Rings: 5

Heavy Atoms: 28

QED Weighted: 0.51

Np Likeness Score: -1.39

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