trans-4-(2-fluoro-3-(trifluorometh-yl)phenoxy)-1-((6-(1,3-thiazol-2-ylamino)pyridin-2-yl)methyl)cyclohexanecarboxylic acid hydrochloride

ID: ALA3923139

PubChem CID: 87251856

Max Phase: Preclinical

Molecular Formula: C23H22ClF4N3O3S

Molecular Weight: 495.50

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cl.O=C(O)[C@]1(Cc2cccc(Nc3nccs3)n2)CC[C@@H](Oc2cccc(C(F)(F)F)c2F)CC1

Standard InChI:  InChI=1S/C23H21F4N3O3S.ClH/c24-19-16(23(25,26)27)4-2-5-17(19)33-15-7-9-22(10-8-15,20(31)32)13-14-3-1-6-18(29-14)30-21-28-11-12-34-21;/h1-6,11-12,15H,7-10,13H2,(H,31,32)(H,28,29,30);1H/t15-,22-;

Standard InChI Key:  CDUNWQDJXVYZLJ-PGIBDOGXSA-N

Molfile:  

     RDKit          2D

 35 37  0  0  0  0  0  0  0  0999 V2000
    3.2739  -20.7464    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    2.7777  -18.1122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7766  -18.9397    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4913  -19.3525    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2078  -18.9392    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2050  -18.1086    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4896  -17.6995    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9178  -17.6935    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.6339  -18.1033    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6344  -18.9300    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3463  -19.3397    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0616  -18.9281    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0605  -18.1020    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3440  -17.6878    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7760  -19.3406    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7760  -20.1656    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0615  -20.5735    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.0612  -21.3978    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7761  -21.8111    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4930  -21.3942    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4899  -20.5713    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3465  -21.8099    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.6323  -21.3971    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5451  -20.5802    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    4.7383  -20.4083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3254  -21.1225    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8772  -21.7358    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.7708  -18.5081    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4897  -18.9127    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.7617  -17.6832    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.4871  -16.8745    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.0631  -17.6999    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0629  -16.8749    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.3488  -18.1126    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.3458  -17.2873    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  2  0
  3  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  2  1  0
  6  8  1  0
  9  8  1  6
  9 10  1  0
  9 14  1  0
 10 11  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 12 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21 16  1  0
 18 22  1  0
 22 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  2  0
 26 27  1  0
 27 23  2  0
 12 28  1  1
 28 29  1  0
 28 30  2  0
  7 31  1  0
  2 32  1  0
 32 33  1  0
 32 34  1  0
 32 35  1  0
M  END

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: 495.50

Molecular Weight (Monoisotopic): 495.1240

AlogP: 6.07

#Rotatable Bonds: 7

Polar Surface Area: 84.34

Molecular Species: ACID

HBA: 6

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 4.17

CX Basic pKa: 2.79

CX LogP: 5.78

CX LogD: 2.96

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.39

Np Likeness Score: -0.89

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):

• Patent Bioactivity Data