Methyl (3-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4-(4-methylpiperazin-1-yl)phenyl)-1H-1,2,3-triazole-4-carboxylate

ID: ALA4868706

PubChem CID: 141725708

Max Phase: Preclinical

Molecular Formula: C23H25ClFN7O3

Molecular Weight: 501.95

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  COC(=O)c1cn(-c2ccc(N3CCN(C)CC3)c(NC(=O)c3cc(N)c(F)c(C)c3Cl)c2)nn1

Standard InChI:  InChI=1S/C23H25ClFN7O3/c1-13-20(24)15(11-16(26)21(13)25)22(33)27-17-10-14(32-12-18(28-29-32)23(34)35-3)4-5-19(17)31-8-6-30(2)7-9-31/h4-5,10-12H,6-9,26H2,1-3H3,(H,27,33)

Standard InChI Key:  SKNBJKQSMQVYLP-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 35 38  0  0  0  0  0  0  0  0999 V2000
   10.4808   -8.6327    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.8216   -8.1526    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.0722   -7.3754    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.8894   -7.3754    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1441   -8.1526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3696   -6.7163    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1841   -6.8003    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.0394   -5.9690    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.4807   -9.4499    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1898   -9.8586    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1898  -10.6758    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4806  -11.0843    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7757  -10.6757    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7757   -9.8585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4806  -11.9015    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.1897  -12.3101    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1896  -13.1273    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    9.7756  -13.1273    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7756  -12.3101    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4805  -14.3531    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6038  -10.6758    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3129  -11.0845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0220  -10.6759    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7269  -11.0845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7269  -11.9017    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0219  -12.3103    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3128  -11.9016    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6038   -9.8586    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.8947  -11.0844    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.4360  -10.6760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4360  -12.3103    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   14.0220   -9.8587    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   14.0219  -13.1275    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.2248   -5.8849    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  2  0
  3  4  1  0
  4  5  2  0
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 19 20  1  0
 15 20  1  0
 18 21  1  0
 12 15  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
 23 28  2  0
 22 29  2  0
 22 30  1  0
 25 31  1  0
 26 32  1  0
 24 33  1  0
 27 34  1  0
 11 30  1  0
  1  9  1  0
  8 35  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4868706

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 501.95

Molecular Weight (Monoisotopic): 501.1691

AlogP: 2.74

#Rotatable Bonds: 5

Polar Surface Area: 118.61

Molecular Species: NEUTRAL

HBA: 9

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 7.60

CX LogP: 3.35

CX LogD: 2.93

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.40

Np Likeness Score: -1.92

References

1. Chen W, Chen X, Li D, Wang X, Long G, Jiang Z, You Q, Guo X..  (2021)  Discovery of a potent MLL1 and WDR5 protein-protein interaction inhibitor with in vivo antitumor activity.,  223  [PMID:34225179] [10.1016/j.ejmech.2021.113677]

2. Karatas, Hacer H, Townsend, Elizabeth C EC, Bernard, Denzil D, Dou, Yali Y and Wang, Shaomeng S.  2010-07-22  Analysis of the binding of mixed lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the design of inhibitors of the MLL1-WDR5 interaction.  [PMID:20575550]

3. Bolshan, Yuri Y and 16 more authors.  2013-03-14  Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction.  [PMID:24900672]

4. Getlik, Matthäus M and 17 more authors.  2016-03-24  Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1).  [PMID:26958703]

5. Li, Dong-Dong DD and 9 more authors.  2016-08-08  Structure-based design and synthesis of small molecular inhibitors disturbing the interaction of MLL1-WDR5.  [PMID:27116709]

6. Li, Dong-Dong DD and 8 more authors.  2016-11-29  High-affinity small molecular blockers of mixed lineage leukemia 1 (MLL1)-WDR5 interaction inhibit MLL1 complex H3K4 methyltransferase activity.  [PMID:27598236]

7. Li, Dong-Dong DD and 5 more authors.  2016-11-15  Structure-based design of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage leukemia 1 (MLL1)-WDR5 interaction.  [PMID:27720555]

8. Wang, Feng F and 17 more authors.  2018-07-12  Discovery of Potent 2-Aryl-6,7-dihydro-5 H-pyrrolo[1,2- a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design.  [PMID:29889518]

9. Ye, Xiaoqing X and 11 more authors.  2019-02-15  The identification of novel small-molecule inhibitors targeting WDR5-MLL1 interaction through fluorescence polarization based high-throughput screening.  [PMID:30626558]

10. Tian, Jianhua and 24 more authors.  2020-01-23  Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core.  [PMID:31858797]

11. Chacón Simon, Selena and 14 more authors.  2020-04-23  Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design.  [PMID:32223236]

Source

Source(1):

• Scientific Literature