(E)-4-(dimethylamino)-N-(3-((methyl(2-(1-(4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-8-yl)-1H-pyrazol-4-yl)ethyl)amino)methyl)phenyl)but-2-enamide

ID: ALA5285949

Max Phase: Preclinical

Molecular Formula: C26H30N8O2

Molecular Weight: 486.58

Names and Identifiers

Canonical SMILES:  CN(C)C/C=C/C(=O)Nc1cccc(CN(C)CCc2cnn(-c3nccc4c(=O)[nH]cnc34)c2)c1

Standard InChI:  InChI=1S/C26H30N8O2/c1-32(2)12-5-8-23(35)31-21-7-4-6-19(14-21)16-33(3)13-10-20-15-30-34(17-20)25-24-22(9-11-27-25)26(36)29-18-28-24/h4-9,11,14-15,17-18H,10,12-13,16H2,1-3H3,(H,31,35)(H,28,29,36)/b8-5+

Standard InChI Key:  PQJJDKDPHAZPEX-VMPITWQZSA-N

Molfile:  

 
     RDKit          2D

 36 39  0  0  0  0  0  0  0  0999 V2000
   -2.5400   -0.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8255    0.3956    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1110   -0.0167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1110   -0.8417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3966   -1.2543    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3178   -0.8417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3178   -0.0167    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3966    0.3956    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3966    1.2206    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8255   -1.2543    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8255   -2.0793    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1581   -2.5642    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4129   -3.3488    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9280   -4.0162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1076   -3.9300    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2279   -3.1763    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2569   -2.5089    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0484   -3.0901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3840   -2.3365    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2044   -2.2502    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5400   -1.4965    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0551   -0.8291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2345   -0.9153    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7496   -0.2479    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.0852    0.5057    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6002    1.1731    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9057    0.5920    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.8990   -1.6690    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2379   -3.3488    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4929   -2.5642    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5400   -0.8417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9358    1.9271    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4507    2.5946    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7863    3.3486    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3012    4.0162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6116    3.3486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  2  1  0
  4  3  2  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  3  8  1  0
  8  9  2  0
 10  4  1  0
 10 11  1  0
 12 11  1  0
 12 13  2  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 16 18  1  0
 18 19  1  0
 20 19  2  0
 21 20  1  0
 22 21  2  0
 23 22  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 25 27  2  0
 28 23  2  0
 19 28  1  0
 13 29  1  0
 29 30  2  0
 30 11  1  0
 31 10  2  0
  1 31  1  0
 26 32  2  0
 32 33  1  0
 33 34  1  0
 34 35  1  0
 34 36  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5285949

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 486.58

Molecular Weight (Monoisotopic): 486.2492

AlogP: 2.23

#Rotatable Bonds: 10

Polar Surface Area: 112.04

Molecular Species: BASE

HBA: 8

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.06

CX Basic pKa: 8.97

CX LogP: 1.67

CX LogD: -0.64

Aromatic Rings: 4

Heavy Atoms: 36

QED Weighted: 0.33

Np Likeness Score: -1.43

References

1. Fu YD, Huang MJ, Guo JW, You YZ, Liu HM, Huang LH, Yu B..  (2020)  Targeting histone demethylase KDM5B for cancer treatment.,  208  [PMID:32883639] [10.1016/j.ejmech.2020.112760]

2. Sayegh, Joyce J and 9 more authors.  2013-03-29  Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen.  [PMID:23408432]

3. Bavetsias, Vassilios and 42 more authors.  2016-02-25  8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.  [PMID:26741168]

4. Labadie, Sharada S SS and 19 more authors.  2016-09-15  Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.  [PMID:27499454]

5. Zheng, Yi-Chao YC and 5 more authors.  2019-01-01  Lysine demethylase 5B (KDM5B): A potential anti-cancer drug target.  [PMID:30343192]

6. Horton, John R and 22 more authors.  2018-12-13  Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A.  [PMID:30392349]

7. Le Bihan, Yann-Vaï and 28 more authors.  2019-09-01  C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays.  [PMID:31158747]

8. Zhao, Bing and 8 more authors.  2020-04-15  Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B).  [PMID:32155529]

Source

Source(1):

• Scientific Literature