N-methyl-N-(3-((2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)methyl)pyridin-2-yl)methanesulfonamide

ID: ALA1084546

Cas Number: 717907-75-0

PubChem CID: 11713159

Product Number: P126147, Order Now?

Max Phase: Phase

Molecular Formula: C21H20F3N7O3S

Molecular Weight: 507.50

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Pf-00562271 | Pf-562271 besilate | PF 562271 | PF-562271 | PF-562271|717907-75-0|PF-00562271 free base|PF-562271 free base|PF562271|PF 562271|CHEMBL1084546|N-METHYL-N-[3-[[[2-[(2-OXO-2,3-DIHYDRO-1H-INDOL-5-YL)AMINO]-5-TRIFLUOROMETHYLPYRIMIDIN-4-YL]AMINO]METHYL]PYRIDIN-2-YL]METHANESULFONAMIDE|717907-75-0 (free base)|K5BX8ZA7UF|N-methyl-N-(3-(((2-((2-oxoindolin-5-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)methyl)pyridin-2-yl)methanesulfonamide|N-[3-[[[2-[(2,3-Dihydro-2-oxo-1H-indol-5-yl)amiShow More⌵

Canonical SMILES:  CN(c1ncccc1CNc1nc(Nc2ccc3c(c2)CC(=O)N3)ncc1C(F)(F)F)S(C)(=O)=O

Standard InChI:  InChI=1S/C21H20F3N7O3S/c1-31(35(2,33)34)19-12(4-3-7-25-19)10-26-18-15(21(22,23)24)11-27-20(30-18)28-14-5-6-16-13(8-14)9-17(32)29-16/h3-8,11H,9-10H2,1-2H3,(H,29,32)(H2,26,27,28,30)

Standard InChI Key:  MZDKLVOWGIOKTN-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 35 38  0  0  0  0  0  0  0  0999 V2000
    8.1994   -6.1289    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.1982   -6.9484    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9063   -7.3574    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.6159   -6.9480    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6131   -6.1253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9045   -5.7200    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3193   -5.7140    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0285   -6.1200    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.3162   -4.8969    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   11.0238   -5.2994    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    7.4902   -7.3565    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.4896   -8.1737    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7814   -8.5801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1987   -9.3941    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1962   -8.5790    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4883   -9.8066    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7822   -9.4013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1785   -9.9477    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5117  -10.6907    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3211  -10.6033    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.1050  -11.3995    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.3243   -7.3554    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3256   -8.1726    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0339   -8.5801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0306   -9.3947    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7381   -9.8021    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4462   -9.3923    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4423   -8.5709    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.7342   -8.1672    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7282   -7.3500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.4329   -6.9362    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   11.0175   -6.9466    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.1436   -7.3396    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8493   -6.3518    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.8357   -6.2239    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
  7  8  1  0
  7  9  1  0
  7 10  1  0
  2 11  1  0
 11 12  1  0
 12 13  2  0
 13 17  1  0
 16 14  1  0
 14 15  2  0
 15 12  1  0
 16 17  2  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 16  1  0
 19 21  2  0
  4 22  1  0
 22 23  1  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  2  0
 29 24  1  0
 29 30  1  0
 30 31  1  0
 30 32  1  0
 31 33  1  0
 31 34  2  0
 31 35  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA1084546

   PF-562271

2. Alternative Forms:

   

   ALA1084546

   PF-00562271

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: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 507.50

Molecular Weight (Monoisotopic): 507.1300

AlogP: 3.14

#Rotatable Bonds: 7

Polar Surface Area: 129.21

Molecular Species: NEUTRAL

HBA: 8

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.34

CX Basic pKa: 4.26

CX LogP: 1.91

CX LogD: 1.91

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.44

Np Likeness Score: -1.59

References

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3. PubChem BioAssay data set, 

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5. Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute,  [10.6019/CHEMBL1201861]

6. Gao C, Cahya S, Nicolaou CA, Wang J, Watson IA, Cummins DJ, Iversen PW, Vieth M..  (2013)  Selectivity data: assessment, predictions, concordance, and implications.,  56  (17): [PMID:23937569] [10.1021/jm400798j]

7. Grädler U, Bomke J, Musil D, Dresing V, Lehmann M, Hölzemann G, Greiner H, Esdar C, Krier M, Heinrich T..  (2013)  Fragment-based discovery of focal adhesion kinase inhibitors.,  23  (19): [PMID:23973211] [10.1016/j.bmcl.2013.07.050]

8. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

9. Unpublished dataset, 

10. Farand J, Mai N, Chandrasekhar J, Newby ZE, Van Veldhuizen J, Loyer-Drew J, Venkataramani C, Guerrero J, Kwok A, Li N, Zherebina Y, Wilbert S, Zablocki J, Phillips G, Watkins WJ, Mourey R, Notte GT..  (2016)  Selectivity switch between FAK and Pyk2: Macrocyclization of FAK inhibitors improves Pyk2 potency.,  26  (24): [PMID:27876318] [10.1016/j.bmcl.2016.10.092]

11. Klaeger S, Heinzlmeir S and Wilhelm M et al.  (2017)  The target landscape of clinical kinase drugs.,  358  (6367): [PMID:29191878] [10.1126/science.aan4368]

12. Chadha N, Silakari O..  (2017)  Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.,  134  [PMID:28412530] [10.1016/j.ejmech.2017.04.003]

13. Kamada Y, Sakai N, Sogabe S, Ida K, Oki H, Sakamoto K, Lane W, Snell G, Iida M, Imaeda Y, Sakamoto J, Matsui J..  (2017)  Discovery of a B-Cell Lymphoma 6 Protein-Protein Interaction Inhibitor by a Biophysics-Driven Fragment-Based Approach.,  60  (10): [PMID:28471657] [10.1021/acs.jmedchem.7b00313]

14. Su Y, Li R, Ning X, Lin Z, Zhao X, Zhou J, Liu J, Jin Y, Yin Y..  (2019)  Discovery of 2,4-diarylaminopyrimidine derivatives bearing dithiocarbamate moiety as novel FAK inhibitors with antitumor and anti-angiogenesis activities.,  177  [PMID:31129452] [10.1016/j.ejmech.2019.05.048]

15. Xie H,Lin X,Zhang Y,Tan F,Chi B,Peng Z,Dong W,An D.  (2020)  Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors.,  30  (21.0): [PMID:32784087] [10.1016/j.bmcl.2020.127459]

16. 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]

17. Lu Y, Sun H..  (2020)  Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK).,  63  (23.0): [PMID:33058670] [10.1021/acs.jmedchem.0c01248]

18. Tan H, Liu Y, Gong C, Zhang J, Huang J, Zhang Q..  (2021)  Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents.,  223  [PMID:34214842] [10.1016/j.ejmech.2021.113670]

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20. Ai Y, Hwang L, MacKerell AD, Melnick A, Xue F..  (2021)  Progress toward B-Cell Lymphoma 6 BTB Domain Inhibitors for the Treatment of Diffuse Large B-Cell Lymphoma and Beyond.,  64  (8.0): [PMID:33844535] [10.1021/acs.jmedchem.0c01686]

Source

Source(7):

• Scientific Literature
• Sanger Institute Genomics of Drug Sensitivity in Cancer
• PubChem BioAssays
• Clinical Candidates
• AstraZeneca Deposited Data
• Kuster lab chemical proteomics drug profiling
• Fraunhofer HDAC6