5-(trans-4-(3-chloro-2-fluorophenoxy)-1-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)cyclohexyl)-1,3,4-oxadiazol-2(3H)-one

ID: ALA3966216

PubChem CID: 24853233

Max Phase: Preclinical

Molecular Formula: C23H22ClFN6O3

Molecular Weight: 484.92

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=c1[nH]nc([C@]2(Cc3cccc(Nc4cc[nH]n4)n3)CC[C@@H](Oc3cccc(Cl)c3F)CC2)o1

Standard InChI:  InChI=1S/C23H22ClFN6O3/c24-16-4-2-5-17(20(16)25)33-15-7-10-23(11-8-15,21-30-31-22(32)34-21)13-14-3-1-6-18(27-14)28-19-9-12-26-29-19/h1-6,9,12,15H,7-8,10-11,13H2,(H,31,32)(H2,26,27,28,29)/t15-,23-

Standard InChI Key:  LLROFEFDEFKWQN-CWSKOGRWSA-N

Molfile:  

     RDKit          2D

 34 38  0  0  0  0  0  0  0  0999 V2000
   33.8509   -2.8957    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.8497   -3.7229    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.5645   -4.1358    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.2809   -3.7224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.2780   -2.8920    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.5627   -2.4829    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.9909   -2.4768    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   36.7069   -2.8867    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.7073   -3.7133    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.4192   -4.1230    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.1346   -3.7113    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.1335   -2.8855    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.4170   -2.4712    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.8490   -4.1239    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.8490   -4.9488    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.1345   -5.3568    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   38.1342   -6.1810    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.8491   -6.5944    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.5659   -6.1774    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.5627   -5.3546    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.4194   -6.5931    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.7052   -6.1803    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.8437   -3.2915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.5602   -1.6579    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   33.1363   -2.4834    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   36.6182   -5.3635    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.8113   -5.1915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.3985   -5.9058    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   35.9503   -6.5190    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   39.6002   -3.6184    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   40.1448   -2.9999    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   39.7249   -2.2908    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.9208   -2.4711    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   40.0520   -1.5334    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  1  0
  5  7  1  0
  8  7  1  6
  8  9  1  0
  8 13  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  1  0
 11 14  1  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 15  1  0
 17 21  1  0
 21 22  1  0
 11 23  1  1
  6 24  1  0
  1 25  1  0
 22 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  1  0
 29 22  2  0
 23 30  2  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 23  1  0
 32 34  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA3966216

   5-[4-(3-chloro-2-fluorophenoxy)-1-[[6-(1H-pyrazol-5-ylamino)pyridin-2-yl]methyl]cyclohexyl]-3H-1,3,4-oxadiazol-2-one

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: 484.92

Molecular Weight (Monoisotopic): 484.1426

AlogP: 4.52

#Rotatable Bonds: 7

Polar Surface Area: 121.72

Molecular Species: NEUTRAL

HBA: 7

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 7.62

CX Basic pKa: 3.76

CX LogP: 5.34

CX LogD: 5.16

Aromatic Rings: 4

Heavy Atoms: 34

QED Weighted: 0.35

Np Likeness Score: -0.82

References

1.  (2008)  Novel aminopyridine derivatives having aurora a selective inhibitory action, 

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):

• Patent Bioactivity Data