2-chloro-N-(3-((methyl(2-(1-(4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-8-yl)-1H-pyrazol-4-yl)ethyl)amino)methyl)phenyl)acetamide

ID: ALA5274997

Max Phase: Preclinical

Molecular Formula: C22H22ClN7O2

Molecular Weight: 451.92

Names and Identifiers

Canonical SMILES:  CN(CCc1cnn(-c2nccc3c(=O)[nH]cnc23)c1)Cc1cccc(NC(=O)CCl)c1

Standard InChI:  InChI=1S/C22H22ClN7O2/c1-29(12-15-3-2-4-17(9-15)28-19(31)10-23)8-6-16-11-27-30(13-16)21-20-18(5-7-24-21)22(32)26-14-25-20/h2-5,7,9,11,13-14H,6,8,10,12H2,1H3,(H,28,31)(H,25,26,32)

Standard InChI Key:  IIYIUKHXJRLSGL-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 32 35  0  0  0  0  0  0  0  0999 V2000
   -2.5400    1.0277    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8255    1.4402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1110    1.0277    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1110    0.2027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3966   -0.2097    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3178    0.2027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3178    1.0277    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3966    1.4402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3966    2.2652    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8255   -0.2097    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8255   -1.0347    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1581   -1.5196    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4129   -2.3042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9280   -2.9716    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1076   -2.8854    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2279   -2.1318    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2569   -1.4643    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0484   -2.0455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3840   -1.2919    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2044   -1.2056    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5400   -0.4519    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0551    0.2154    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2345    0.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7496    0.7966    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.0852    1.5503    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6002    2.2177    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9057    1.6365    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.8990   -0.6244    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2379   -2.3042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4929   -1.5196    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5400    0.2027    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.9359    2.9716    0.0000 Cl  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
  3  8  1  0
  7  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  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5274997

   ---

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: 451.92

Molecular Weight (Monoisotopic): 451.1524

AlogP: 2.36

#Rotatable Bonds: 8

Polar Surface Area: 108.80

Molecular Species: BASE

HBA: 7

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.04

CX Basic pKa: 8.53

CX LogP: 1.75

CX LogD: 0.75

Aromatic Rings: 4

Heavy Atoms: 32

QED Weighted: 0.40

Np Likeness Score: -1.82

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