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

ID: ALA4866458

PubChem CID: 141725705

Max Phase: Preclinical

Molecular Formula: C22H23ClFN7O3

Molecular Weight: 487.92

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1c(F)c(N)cc(C(=O)Nc2cc(-n3cc(C(=O)O)nn3)ccc2N2CCN(C)CC2)c1Cl

Standard InChI:  InChI=1S/C22H23ClFN7O3/c1-12-19(23)14(10-15(25)20(12)24)21(32)26-16-9-13(31-11-17(22(33)34)27-28-31)3-4-18(16)30-7-5-29(2)6-8-30/h3-4,9-11H,5-8,25H2,1-2H3,(H,26,32)(H,33,34)

Standard InChI Key:  ULYZOXPTGWTZKW-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 34 37  0  0  0  0  0  0  0  0999 V2000
    9.2756   -7.1469    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.6165   -6.6668    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.8671   -5.8896    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.6843   -5.8896    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9389   -6.6668    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1644   -5.2305    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9790   -5.3145    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.8342   -4.4832    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.2756   -7.9641    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9846   -8.3728    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9846   -9.1900    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2755   -9.5985    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5706   -9.1899    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5706   -8.3727    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2755  -10.4157    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.9845  -10.8243    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9845  -11.6415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2754  -12.0501    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.5704  -11.6415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5705  -10.8243    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2753  -12.8673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3987   -9.1900    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1077   -9.5987    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8168   -9.1901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5218   -9.5987    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5217  -10.4159    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8168  -10.8245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1077  -10.4158    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3987   -8.3728    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.6895   -9.5986    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.2309   -9.1902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2308  -10.8245    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   12.8169   -8.3729    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   12.8167  -11.6417    0.0000 N   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
  1  5  1  0
  6  7  2  0
  6  8  1  0
  4  6  1  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
  9 14  2  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 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
M  END

Alternative Forms

1. Parent:

   

   ALA4866458

   ---

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: 487.92

Molecular Weight (Monoisotopic): 487.1535

AlogP: 2.65

#Rotatable Bonds: 5

Polar Surface Area: 129.61

Molecular Species: ACID

HBA: 8

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 3.02

CX Basic pKa: 7.62

CX LogP: 0.47

CX LogD: 0.31

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.47

Np Likeness Score: -1.87

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