1-(3-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4-(4-methylpiperazin-1-yl)phenyl)-N-(1-methylpiperidin-4-yl)-1H-1,2,3-triazole-4-carboxamide

ID: ALA4869658

PubChem CID: 141725709

Max Phase: Preclinical

Molecular Formula: C28H35ClFN9O2

Molecular Weight: 584.10

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1c(F)c(N)cc(C(=O)Nc2cc(-n3cc(C(=O)NC4CCN(C)CC4)nn3)ccc2N2CCN(C)CC2)c1Cl

Standard InChI:  InChI=1S/C28H35ClFN9O2/c1-17-25(29)20(15-21(31)26(17)30)27(40)33-22-14-19(4-5-24(22)38-12-10-37(3)11-13-38)39-16-23(34-35-39)28(41)32-18-6-8-36(2)9-7-18/h4-5,14-16,18H,6-13,31H2,1-3H3,(H,32,41)(H,33,40)

Standard InChI Key:  AQQCBBDWEBSYPT-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

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    9.5145   -9.1631    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.7549   -8.3842    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.5720   -8.3691    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8366   -9.1444    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0406   -7.7029    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8570   -7.7719    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.7011   -6.9594    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.4548   -5.6961    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9820   -6.3664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1698   -6.2933    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8261   -5.5498    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2948   -4.8795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1112   -4.9568    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.1957  -10.4529    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   10.2328  -12.9040    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.9472  -13.3000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9623  -14.1171    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2588  -14.5381    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.5444  -14.1380    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5334  -13.3209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2739  -15.3551    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3391  -11.6450    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0535  -12.0410    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0645  -12.8581    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7789  -13.2541    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4824  -12.8372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4673  -12.0201    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7529  -11.6200    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3240  -10.8280    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.6356  -12.0619    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.7899  -14.0711    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1927  -13.2332    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   12.3651  -13.2791    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   15.1708  -11.5991    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.5827   -4.2893    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
  1  5  1  0
  6  7  2  0
  6  8  1  0
  4  6  1  0
  9 10  1  0
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 13 14  1  0
  9 14  1  0
  8 11  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
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 15 20  2  0
 21 22  1  0
 22 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 21 26  1  0
 24 27  1  0
 18 21  1  0
 28 29  1  0
 29 30  1  0
 30 31  2  0
 31 32  1  0
 32 33  2  0
 33 34  1  0
 29 34  2  0
 28 35  2  0
 28 36  1  0
 31 37  1  0
 32 38  1  0
 30 39  1  0
 33 40  1  0
 17 36  1  0
  1 15  1  0
 14 41  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4869658

   ---

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: 584.10

Molecular Weight (Monoisotopic): 583.2586

AlogP: 2.78

#Rotatable Bonds: 6

Polar Surface Area: 124.65

Molecular Species: NEUTRAL

HBA: 9

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.69

CX Basic pKa: 8.42

CX LogP: 2.64

CX LogD: 1.17

Aromatic Rings: 3

Heavy Atoms: 41

QED Weighted: 0.38

Np Likeness Score: -1.86

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