N1-(3-(3-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4-(4-methylpiperazi-n-1-yl)phenyl)prop-2-yn-1-yl)-N4,N4-dimethylterephthalamide

ID: ALA4868412

PubChem CID: 164623801

Max Phase: Preclinical

Molecular Formula: C32H34ClFN6O3

Molecular Weight: 605.11

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

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

Standard InChI: InChI=1S/C32H34ClFN6O3/c1-20-28(33)24(19-25(35)29(20)34)31(42)37-26-18-21(7-12-27(26)40-16-14-39(4)15-17-40)6-5-13-36-30(41)22-8-10-23(11-9-22)32(43)38(2)3/h7-12,18-19H,13-17,35H2,1-4H3,(H,36,41)(H,37,42)

Standard InChI Key: USSJDXKXMPIJJT-UHFFFAOYSA-N

Molfile:

 
     RDKit          2D

 43 46  0  0  0  0  0  0  0  0999 V2000
   12.7684   -9.9493    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4765  -10.3555    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1865   -9.9486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8947  -10.3589    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8927  -11.1761    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1826  -11.5830    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4745  -11.1727    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7703   -9.1321    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.0624  -10.3562    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6006   -9.9520    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3543   -9.9460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6443  -10.3529    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9403   -9.9426    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9422   -9.1254    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6482   -8.7185    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3563   -9.1288    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6464  -11.1700    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3504  -11.5803    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3526  -12.3975    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6425  -12.8044    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.9344  -12.3941    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9364  -11.5770    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6406  -13.6216    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6501   -7.9013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6521   -7.0841    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6540   -6.2669    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9479   -5.0394    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2397   -4.6292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6538   -4.6325    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.9459   -5.8566    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6008  -11.5863    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   14.1885   -9.1314    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   14.1807  -12.4002    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.2426   -3.8122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5354   -3.4020    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8250   -3.8102    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8264   -4.6328    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5342   -5.0393    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1174   -3.4014    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1176   -2.5842    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.4096   -3.8099    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.7020   -3.4011    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4094   -4.6271    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  2  7  2  0
  1  8  2  0
  1  9  1  0
  4 10  1  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 16  1  0
 11 16  2  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 17 22  1  0
 20 23  1  0
 12 17  1  0
 24 25  3  0
 25 26  1  0
 27 28  1  0
 27 29  2  0
 27 30  1  0
 26 30  1  0
 15 24  1  0
  9 11  1  0
  5 31  1  0
  3 32  1  0
  6 33  1  0
 28 34  2  0
 34 35  1  0
 35 36  2  0
 36 37  1  0
 37 38  2  0
 38 28  1  0
 36 39  1  0
 39 40  2  0
 39 41  1  0
 41 42  1  0
 41 43  1  0
M  END

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

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: 605.11	Molecular Weight (Monoisotopic): 604.2365	AlogP: 3.86	#Rotatable Bonds: 6
Polar Surface Area: 111.01	Molecular Species: NEUTRAL	HBA: 6	HBD: 3
#RO5 Violations: 1	HBA (Lipinski): 9	HBD (Lipinski): 4	#RO5 Violations (Lipinski): 1
CX Acidic pKa: ┄	CX Basic pKa: 7.60	CX LogP: 4.02	CX LogD: 3.61
Aromatic Rings: 3	Heavy Atoms: 43	QED Weighted: 0.29	Np Likeness Score: -1.49

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]

N1-(3-(3-(5-amino-2-chloro-4-fluoro-3-methylbenzamido)-4-(4-methylpiperazi-n-1-yl)phenyl)prop-2-yn-1-yl)-N4,N4-dimethylterephthalamide

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source