1-(1H-benzo[d]imidazol-6-yl)-8-(p-tolyl)-1H-imidazo-[4,5-c][1,7]naphthyridine

ID: ALA3987154

PubChem CID: 134156318

Max Phase: Preclinical

Molecular Formula: C23H16N6

Molecular Weight: 376.42

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1ccc(-c2cc3c(cn2)ncc2ncn(-c4ccc5nc[nH]c5c4)c23)cc1

Standard InChI:  InChI=1S/C23H16N6/c1-14-2-4-15(5-3-14)19-9-17-21(10-24-19)25-11-22-23(17)29(13-28-22)16-6-7-18-20(8-16)27-12-26-18/h2-13H,1H3,(H,26,27)

Standard InChI Key:  BBZPNSXBLMAPPM-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 29 34  0  0  0  0  0  0  0  0999 V2000
   18.0635  -16.1787    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7686  -15.7698    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.4772  -16.1751    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4779  -16.9941    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1865  -17.4012    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8947  -16.9904    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8900  -16.1682    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.1809  -15.7649    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7704  -17.4072    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.0609  -16.9951    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4497  -17.5424    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.7814  -18.2929    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5976  -18.2092    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.1414  -18.8155    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.8852  -19.5926    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.4837  -19.2522    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.9376  -18.6471    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.2380  -20.0354    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4286  -20.2039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.3388  -21.0257    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.0926  -21.3651    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.6483  -20.7530    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.6082  -17.3934    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.6110  -18.2126    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.3236  -18.6155    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.0303  -18.1991    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.0199  -17.3756    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.3068  -16.9763    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7423  -18.6001    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  2  0
 24 25  1  0
 25 26  2  0
 26 27  1  0
 27 28  2  0
 28 23  1  0
 26 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3987154

   ---

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: 376.42

Molecular Weight (Monoisotopic): 376.1436

AlogP: 4.82

#Rotatable Bonds: 2

Polar Surface Area: 72.28

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.22

CX Basic pKa: 6.31

CX LogP: 3.91

CX LogD: 3.88

Aromatic Rings: 6

Heavy Atoms: 29

QED Weighted: 0.47

Np Likeness Score: -1.12

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