N-(2-(4-sulfamoylphenylamino)-5,6-dihydrobenzo[h]quinazolin-8-yl)cyclopentanecarboxamide

ID: ALA1083176

PubChem CID: 46890285

Max Phase: Preclinical

Molecular Formula: C24H25N5O3S

Molecular Weight: 463.56

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  NS(=O)(=O)c1ccc(Nc2ncc3c(n2)-c2ccc(NC(=O)C4CCCC4)cc2CC3)cc1

Standard InChI:  InChI=1S/C24H25N5O3S/c25-33(31,32)20-10-7-18(8-11-20)28-24-26-14-17-6-5-16-13-19(9-12-21(16)22(17)29-24)27-23(30)15-3-1-2-4-15/h7-15H,1-6H2,(H,27,30)(H2,25,31,32)(H,26,28,29)

Standard InChI Key:  DYWJQCINNODPCV-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 33 37  0  0  0  0  0  0  0  0999 V2000
    5.7625   -8.7667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.1792   -9.4833    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    6.5915   -8.7642    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.8997  -11.1444    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6162  -10.7310    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6133   -9.9005    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.8979   -9.4914    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9567  -11.1402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9578  -11.9661    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2386  -12.3790    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4727  -11.9653    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3313  -11.1424    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.0451  -10.7288    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7569  -11.1406    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4702  -10.7277    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4694   -9.9018    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7492   -9.4906    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0388   -9.9059    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.8983   -9.8976    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2424  -10.7289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4734  -11.1460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1885  -10.7370    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1941   -9.9091    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4784   -9.4920    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2430   -9.9028    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6721  -12.3789    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3868  -11.9668    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3872  -11.1418    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1010  -12.3797    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8561  -12.0447    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4078  -12.6581    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9948  -13.3724    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1880  -13.2003    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 15 16  2  0
 20  8  1  0
 16 17  1  0
  2  1  2  0
 17 18  2  0
 18 13  1  0
 16  2  1  0
  8  9  2  0
  2 19  1  0
 20 21  2  0
  4  5  2  0
  9 10  1  0
  3  2  2  0
 10 11  2  0
 11 21  1  0
  5  6  1  0
 20 25  1  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  1  0
  5 12  1  0
  9 26  1  0
 26 27  1  0
 12 13  1  0
 27 28  2  0
  6  7  2  0
 27 29  1  0
 29 30  1  0
 13 14  2  0
  7 23  1  0
 14 15  1  0
 22  4  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1083176

   N-(2-(4-sulfamoylphenylamino)-5,6-dihydrobenzo[h]quinazolin-8-yl)cyclopentanecarboxamide

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: 463.56

Molecular Weight (Monoisotopic): 463.1678

AlogP: 3.76

#Rotatable Bonds: 5

Polar Surface Area: 127.07

Molecular Species: NEUTRAL

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.69

CX Basic pKa: 1.65

CX LogP: 4.28

CX LogD: 4.28

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.53

Np Likeness Score: -1.49

References

1. Crombie AL, Sum FW, Powell DW, Hopper DW, Torres N, Berger DM, Zhang Y, Gavriil M, Sadler TM, Arndt K..  (2010)  Synthesis and biological evaluation of tricyclic anilinopyrimidines as IKKbeta inhibitors.,  20  (12): [PMID:20471256] [10.1016/j.bmcl.2010.04.022]

2. Burke, James R JR and 11 more authors.  2003-01-17  BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice.  [PMID:12403772]

3. Podolin, Patricia L PL and 8 more authors.  2005-01  Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation.  [PMID:15316093]

4. Wen, Danyi D and 14 more authors.  2006-06  A selective small molecule IkappaB Kinase beta inhibitor blocks nuclear factor kappaB-mediated inflammatory responses in human fibroblast-like synoviocytes, chondrocytes, and mast cells.  [PMID:16525037]

5. Mbalaviele, Gabriel G and 13 more authors.  2009-04  A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models.  [PMID:19168710]

6. Nagarajan, Shanthi S and 6 more authors.  2009-04-01  IKKbeta inhibitors identification part I: homology model assisted structure based virtual screening.  [PMID:19285872]

7. Zarrinkar, Patrick P PP and 15 more authors.  2009-10-01  AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).  [PMID:19654408]

8. Bhattarai, Bharat Raj BR and 6 more authors.  2010-02-01  Inhibition of IKK-beta: a new development in the mechanism of the anti-obesity effects of PTP1B inhibitors SA18 and SA32.  [PMID:20044255]

9. Shimizu, Hiroki H and 10 more authors.  2011-08-01  Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 3: exploration of effective compounds in arthritis models.  [PMID:21705219]

10. Huang, Jing-Jie JJ and 9 more authors.  2013-05  Novel IKKβ inhibitors discovery based on the co-crystal structure by using binding-conformation-based and ligand-based method.  [PMID:23501112]

11. Ye, Qing Q and 14 more authors.  2015-03-01  Synthesis and biological evaluation of 3-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-4-(indol-3-yl)-maleimides as potent, selective GSK-3β inhibitors and neuroprotective agents.  [PMID:25662701]

12. Anthony, Nahoum G and 23 more authors.  2017-08-24  Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers.  [PMID:28737909]

Source

Source(1):

• Scientific Literature