(2Z,5Z)-2-((4-Ethylphenyl)imino)-3-methyl-5-((2-(pyridin-2-ylamino)pyridin-4-yl)methylene)thiazolidin-4-one

ID: ALA3913242

PubChem CID: 134142431

Max Phase: Preclinical

Molecular Formula: C23H21N5OS

Molecular Weight: 415.52

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CCc1ccc(/N=C2\S/C(=C\c3ccnc(Nc4ccccn4)c3)C(=O)N2C)cc1

Standard InChI:  InChI=1S/C23H21N5OS/c1-3-16-7-9-18(10-8-16)26-23-28(2)22(29)19(30-23)14-17-11-13-25-21(15-17)27-20-6-4-5-12-24-20/h4-15H,3H2,1-2H3,(H,24,25,27)/b19-14-,26-23-

Standard InChI Key:  KFKPRIMBMAKQFG-QFMGQSSSSA-N

Molfile:  

     RDKit          2D

 30 33  0  0  0  0  0  0  0  0999 V2000
    8.7289  -11.7318    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.2080  -11.0677    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0293  -11.0664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2827  -10.2847    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   10.5105  -11.7289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3290  -11.6395    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8102  -12.3061    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6246  -12.2167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.1058  -12.8792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.9243  -12.7939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4055  -13.4564    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.2199  -13.3711    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5531  -12.6191    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0719  -11.9566    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2534  -12.0461    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9578  -11.4689    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.4725  -10.8064    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.6581  -10.8917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9521  -10.2868    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.1744  -10.0334    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6187   -9.8056    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6174   -8.9843    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3258   -8.5746    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0356   -8.9820    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7481   -8.5723    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7468   -7.7510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4553   -7.3413    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4540   -6.5200    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0330   -7.3435    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3245   -7.7532    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  1  0
  3  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 10 15  1  0
  8 16  2  0
 16 17  1  0
 17 18  2  0
  6 18  1  0
  2 19  1  0
 19 20  1  0
 19 21  1  0
  4 21  1  0
 21 22  2  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  2  0
 26 27  1  0
 27 28  1  0
 26 29  1  0
 29 30  2  0
 23 30  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3913242

   ---

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: 415.52

Molecular Weight (Monoisotopic): 415.1467

AlogP: 5.02

#Rotatable Bonds: 5

Polar Surface Area: 70.48

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 13.46

CX Basic pKa: 4.83

CX LogP: 5.29

CX LogD: 5.29

Aromatic Rings: 3

Heavy Atoms: 30

QED Weighted: 0.59

Np Likeness Score: -1.60

References

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2. Fancelli, Daniele D and 24 more authors.  2006-11-30  1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile.  [PMID:17125279]

3. Yang, Jing J and 11 more authors.  2007-09-15  AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo.  [PMID:17495131]

4. McDermott, Ultan U and 24 more authors.  2007-12-11  Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.  [PMID:18077425]

5. Weiss, Matthew M MM and 30 more authors.  2008-03-27  Evaluation of a series of naphthamides as potent, orally active vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.  [PMID:18324759]

6. Shiotsu, Yukimasa Y and 16 more authors.  2009-08-20  KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation.  [PMID:19541823]

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. Shimomura, Toshiyasu T and 14 more authors.  2010-01  MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel.  [PMID:20053775]

9. Adams, Nicholas D ND and 31 more authors.  2010-05-27  Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase.  [PMID:20420387]

10. Bavetsias, Vassilios V and 21 more authors.  2010-07-22  Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate.  [PMID:20565112]

11. Payton, Marc M and 20 more authors.  2010-12-01  Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines.  [PMID:20935223]

12. Medina, Jesús R JR and 24 more authors.  2011-03-24  Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors.  [PMID:21341675]

13. Mollard, Alexis A and 8 more authors.  2011-12-08  Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors.  [PMID:22247788]

14. Lawrence, Harshani R and 14 more authors.  2012-09-13  Development of o-chlorophenyl substituted pyrimidines as exceptionally potent aurora kinase inhibitors.  [PMID:22803810]

15. Elkins, Jonathan M; Santaguida, Stefano; Musacchio, Andrea and Knapp, Stefan.  2012-09-13  Crystal structure of human aurora B in complex with INCENP and VX-680.  [PMID:22920039]

16. Glaser, Keith B KB and 22 more authors.  2012-12  Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families.  [PMID:22935731]

17. Weïwer, Michel M and 12 more authors.  2012-12-13  A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells.  [PMID:23256033]

18. Li, Jie J and 6 more authors.  2013-07  A thienopyrimidine derivative induces growth inhibition and apoptosis in human cancer cell lines via inhibiting Aurora B kinase activity.  [PMID:23707920]

19. Shiao, Hui-Yi HY and 18 more authors.  2013-07-11  Optimization of ligand and lipophilic efficiency to identify an in vivo active furano-pyrimidine Aurora kinase inhibitor.  [PMID:23808327]

20. Sampson, Peter B PB and 23 more authors.  2015-01-08  The discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor agents.  [PMID:24867403]

21. Alder, Catherine M CM and 18 more authors.  2013-10-10  Identification of a Novel and Selective Series of Itk Inhibitors via a Template-Hopping Strategy.  [PMID:24900590]

22. Jagtap, Ajit Dhananjay AD and 8 more authors.  2014-10-06  Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia.  [PMID:25089810]

23. Carry, Jean-Christophe JC and 32 more authors.  2015-01-08  SAR156497, an exquisitely selective inhibitor of aurora kinases.  [PMID:25369539]

24. An, Ying Y and 7 more authors.  2016-07-01  Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors.  [PMID:27209235]

25. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

26. Barker, Michael D MD and 11 more authors.  2018-11-15  Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease.  [PMID:30249354]

27. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]

28. Fan, Chengcheng and 7 more authors.  2020-03-15  Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition.  [PMID:32058239]

29. Lakkaniga, Naga Rajiv and 5 more authors.  2020-10-01  Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression.  [PMID:32717530]

Source

Source(1):

• Scientific Literature