4-(3-chloro-2-fluorophenoxy)-1-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)cyclohexanecarboxylic acid

ID: ALA3600873

Max Phase: Preclinical

Molecular Formula: C22H21ClFN3O3S

Molecular Weight: 461.95

Molecule Type: Small molecule

Names and Identifiers

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

Standard InChI:  InChI=1S/C22H21ClFN3O3S/c23-16-4-2-5-17(19(16)24)30-15-7-9-22(10-8-15,20(28)29)13-14-3-1-6-18(26-14)27-21-25-11-12-31-21/h1-6,11-12,15H,7-10,13H2,(H,28,29)(H,25,26,27)/t15-,22-

Standard InChI Key:  LCVIRAZGMYMNNT-VVONHTQRSA-N

Molfile:  

     RDKit          2D

 31 34  0  0  0  0  0  0  0  0999 V2000
    1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0031   -3.0008    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3039   -3.7494    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3092   -5.2494    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6108   -5.9949    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9073   -5.2404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9021   -3.7404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6004   -2.9949    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6150   -7.1949    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    0.2721   -5.8530    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2999    2.2084    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6000    1.4585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9117    2.1838    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1965    1.4098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1686   -0.0900    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8558   -0.8156    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5710   -0.0416    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.5115    2.1332    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7960    1.3569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.1607    1.9479    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
  -10.1396    0.8112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.3610   -0.4709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.9011   -0.1267    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.3001    2.2088    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3391    1.6083    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3010    3.4088    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  6  1  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  6
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13  8  1  0
 10 14  1  0
  9 15  1  0
  3 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 17  1  0
 19 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 24  2  0
  3 29  1  1
 29 30  1  0
 29 31  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA3600873

   ---

2. Alternative Forms:

   

   ALA3600873

   4-(3-Chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)pyridin-2-yl]methyl]cyclohexane-1-carboxylic acid;hydrochloride

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: 461.95

Molecular Weight (Monoisotopic): 461.0976

AlogP: 5.71

#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: 4.29

CX Basic pKa: 2.79

CX LogP: 5.54

CX LogD: 2.77

Aromatic Rings: 3

Heavy Atoms: 31

QED Weighted: 0.47

Np Likeness Score: -0.97

References

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2. An Y, Lee E, Yu Y, Yun J, Lee MY, Kang JS, Kim WY, Jeon R..  (2016)  Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors.,  26  (13): [PMID:27209235] [10.1016/j.bmcl.2016.05.017]

3. Kilchmann F, Marcaida MJ, Kotak S, Schick T, Boss SD, Awale M, Gönczy P, Reymond JL..  (2016)  Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening.,  59  (15): [PMID:27391133] [10.1021/acs.jmedchem.6b00709]

4. Chang CF, Lin WH, Ke YY, Lin YS, Wang WC, Chen CH, Kuo PC, Hsu JTA, Uang BJ, Hsieh HP..  (2016)  Discovery of novel inhibitors of Aurora kinases with indazole scaffold: In silico fragment-based and knowledge-based drug design.,  124  [PMID:27573544] [10.1016/j.ejmech.2016.08.026]

5.  (2008)  Novel aminopyridine derivatives having aurora a selective inhibitory action, 

6. Borisa AC, Bhatt HG..  (2017)  A comprehensive review on Aurora kinase: Small molecule inhibitors and clinical trial studies.,  140  [PMID:28918096] [10.1016/j.ejmech.2017.08.045]

7. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

8. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

9. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

10. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

11. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

12. Allegretti PA, Horton TM, Abdolazimi Y, Moeller HP, Yeh B, Caffet M, Michel G, Smith M, Annes JP..  (2020)  Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization.,  28  (1): [PMID:31757680] [10.1016/j.bmc.2019.115193]

13. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

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Source

Source(5):

• Scientific Literature
• Patent Bioactivity Data
• SARS-CoV-2 Screening Data 2020-21
• EUbOPEN Chemogenomic Library
• Fraunhofer HDAC6