4-(5-(4-fluorophenyl)-1H-pyrazol-3-ylamino)benzamide

ID: ALA511337

PubChem CID: 44588220

Max Phase: Preclinical

Molecular Formula: C16H13FN4O

Molecular Weight: 296.31

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  NC(=O)c1ccc(Nc2cc(-c3ccc(F)cc3)[nH]n2)cc1

Standard InChI:  InChI=1S/C16H13FN4O/c17-12-5-1-10(2-6-12)14-9-15(21-20-14)19-13-7-3-11(4-8-13)16(18)22/h1-9H,(H2,18,22)(H2,19,20,21)

Standard InChI Key:  QKAONCSNINNEGU-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 22 24  0  0  0  0  0  0  0  0999 V2000
   13.2583   -6.1209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0833   -6.1209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.3401   -5.3367    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.6708   -4.8500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.0058   -5.3367    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.5660   -6.7867    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2279   -7.5404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7113   -8.2080    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5328   -8.1231    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8685   -7.3648    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.3831   -6.7004    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2210   -5.0821    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.6082   -5.6345    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8243   -5.3774    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2118   -5.9289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3834   -6.7368    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1730   -6.9901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7822   -6.4369    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7713   -7.2899    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9862   -7.0363    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.9443   -8.0966    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.0178   -8.7905    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
 11  6  1  0
  2  6  1  0
  1  2  2  0
  5 12  1  0
 12 13  1  0
  6  7  2  0
 13 14  2  0
  2  3  1  0
 14 15  1  0
  7  8  1  0
 15 16  2  0
  3  4  1  0
 16 17  1  0
  8  9  2  0
 17 18  2  0
 18 13  1  0
  4  5  2  0
 16 19  1  0
  9 10  1  0
 19 20  2  0
  5  1  1  0
 19 21  1  0
 10 11  2  0
  9 22  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA511337

   4-(5-(4-fluorophenyl)-1H-pyrazol-3-ylamino)benzamide

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: 296.31

Molecular Weight (Monoisotopic): 296.1073

AlogP: 3.06

#Rotatable Bonds: 4

Polar Surface Area: 83.80

Molecular Species: NEUTRAL

HBA: 3

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 4.00

CX LogP: 2.87

CX LogD: 2.87

Aromatic Rings: 3

Heavy Atoms: 22

QED Weighted: 0.69

Np Likeness Score: -1.66

References

1. Bamborough P, Drewry D, Harper G, Smith GK, Schneider K..  (2008)  Assessment of chemical coverage of kinome space and its implications for kinase drug discovery.,  51  (24): [PMID:19035792] [10.1021/jm8011036]

2. 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]

3. Oyarzabal, Julen J and 12 more authors.  2010-09-23  Discovery of mitogen-activated protein kinase-interacting kinase 1 inhibitors by a comprehensive fragment-oriented virtual screening approach.  [PMID:20722422]

4. Teo, Theodosia T and 11 more authors.  2015-10-20  An integrated approach for discovery of highly potent and selective Mnk inhibitors: Screening, synthesis and SAR analysis.  [PMID:26408454]

5. Han, Wooseok W and 12 more authors.  2016-04-14  Discovery of a Selective and Potent Inhibitor of Mitogen-Activated Protein Kinase-Interacting Kinases 1 and 2 (MNK1/2) Utilizing Structure-Based Drug Design.  [PMID:27002243]

6. Cherian, Joseph J and 24 more authors.  2016-04-14  Structure-Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells.  [PMID:27011159]

7. Farag, Ahmed Karam AK and 5 more authors.  2017-12-01  Novel LCK/FMS inhibitors based on phenoxypyrimidine scaffold as potential treatment for inflammatory disorders.  [PMID:29107425]

8. Reich, Siegfried H SH and 28 more authors.  2018-04-26  Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition.  [PMID:29526098]

9. Yang, Haiyan H and 32 more authors.  2018-05-24  Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia.  [PMID:29683667]

10. 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]

11. Yuan, Xinrui X and 5 more authors.  2019-04-01  Design, synthesis and biological evaluation of pyridone-aminal derivatives as MNK1/2 inhibitors.  [PMID:30824167]

12. Abdelaziz, Ahmed M AM and 8 more authors.  2019-09-15  Synthesis and evaluation of 2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione derivatives as Mnk inhibitors.  [PMID:31362920]

13. Kwiatkowski, Jacek and 25 more authors.  2020-01-23  Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.  [PMID:31910010]

Source

Source(1):

• Scientific Literature