3'-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-carboxylic acid

ID: ALA4878567

PubChem CID: 164626399

Max Phase: Preclinical

Molecular Formula: C26H26ClFN4O3

Molecular Weight: 496.97

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1c(F)c(N)cc(C(=O)Nc2cc(-c3ccc(C(=O)O)cc3)ccc2N2CCN(C)CC2)c1Cl

Standard InChI:  InChI=1S/C26H26ClFN4O3/c1-15-23(27)19(14-20(29)24(15)28)25(33)30-21-13-18(16-3-5-17(6-4-16)26(34)35)7-8-22(21)32-11-9-31(2)10-12-32/h3-8,13-14H,9-12,29H2,1-2H3,(H,30,33)(H,34,35)

Standard InChI Key:  FMVQTQJEPRFHFC-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

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    8.5577   -6.0029    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5607   -5.1857    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2733   -4.7792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9788   -5.1939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    9.2562   -7.2348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    9.2461   -8.8691    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    9.2763   -3.9620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9848   -3.5596    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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    9.2301  -12.1378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3727   -8.4707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   12.0753   -9.6985    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7808  -10.1132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4893   -9.7067    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4923   -8.8895    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7867   -8.4789    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3798   -7.6536    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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   12.7737  -10.9304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1948  -10.1214    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   11.3627  -10.1051    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   14.2049   -8.4871    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
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 28 35  1  0
  9 31  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4878567

   ---

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: 496.97

Molecular Weight (Monoisotopic): 496.1677

AlogP: 4.74

#Rotatable Bonds: 5

Polar Surface Area: 98.90

Molecular Species: ACID

HBA: 5

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 4.08

CX Basic pKa: 7.61

CX LogP: 2.08

CX LogD: 1.92

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.44

Np Likeness Score: -1.10

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