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

ID: ALA4863061

PubChem CID: 141725706

Max Phase: Preclinical

Molecular Formula: C27H32ClFN8O3

Molecular Weight: 571.06

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1c(F)c(N)cc(C(=O)Nc2cc(-n3cc(C(=O)NC4CCOCC4)nn3)ccc2N2CCN(C)CC2)c1Cl

Standard InChI:  InChI=1S/C27H32ClFN8O3/c1-16-24(28)19(14-20(30)25(16)29)26(38)32-21-13-18(3-4-23(21)36-9-7-35(2)8-10-36)37-15-22(33-34-37)27(39)31-17-5-11-40-12-6-17/h3-4,13-15,17H,5-12,30H2,1-2H3,(H,31,39)(H,32,38)

Standard InChI Key:  WKDPERRTFWPQQI-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 40 44  0  0  0  0  0  0  0  0999 V2000
   10.1848   -9.6358    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    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 O   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
   10.9102  -10.8489    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9211  -11.6659    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2218  -12.0870    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5073  -11.6868    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4964  -10.8698    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   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
  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  1  0
 11 12  1  0
 12 13  1  0
 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
 19 20  1  0
 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
M  END

Alternative Forms

1. Parent:

   

   ALA4863061

   ---

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: 571.06

Molecular Weight (Monoisotopic): 570.2270

AlogP: 2.86

#Rotatable Bonds: 6

Polar Surface Area: 130.64

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: 7.60

CX LogP: 2.58

CX LogD: 2.16

Aromatic Rings: 3

Heavy Atoms: 40

QED Weighted: 0.39

Np Likeness Score: -1.83

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