8-(4-(2-(4-acryloylpiperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one

ID: ALA5276370

Max Phase: Preclinical

Molecular Formula: C20H22N6O2

Molecular Weight: 378.44

Names and Identifiers

Canonical SMILES:  C=CC(=O)C1CCN(CCc2cnn(-c3nccc4c(=O)[nH]cnc34)c2)CC1

Standard InChI:  InChI=1S/C20H22N6O2/c1-2-17(27)15-5-9-25(10-6-15)8-4-14-11-24-26(12-14)19-18-16(3-7-21-19)20(28)23-13-22-18/h2-3,7,11-13,15H,1,4-6,8-10H2,(H,22,23,28)

Standard InChI Key:  WNKDQRDTZMQKLQ-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

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   -1.8303    1.7934    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1158    1.3809    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4014    1.7934    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4014    2.6184    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.3130    1.3809    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3130    0.5560    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4014    0.1434    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1158    0.5560    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8303    0.1434    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5448    0.5560    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8303   -0.6815    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1629   -1.1664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4178   -1.9510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9329   -2.6184    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1124   -2.5322    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2230   -1.7785    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2428   -1.9510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4977   -1.1664    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2620   -1.1109    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0736   -0.3570    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8943   -0.2708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3794   -0.9384    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0437   -1.6923    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3069    0.4438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8943    1.1585    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1321    0.4438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5448    1.1585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  2  1  0
  3  4  1  0
  4  5  2  0
  6  4  1  0
  7  6  1  0
  8  7  2  0
  9  8  1  0
  9  3  2  0
 10  9  1  0
 11 10  2  0
  1 11  1  0
 10 12  1  0
 13 12  1  0
 13 14  2  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 14 18  1  0
 18 19  2  0
 19 12  1  0
 20 17  1  0
 21 20  1  0
 22 21  1  0
 23 22  1  0
 24 23  1  0
 17 24  1  0
 22 25  1  0
 25 26  2  0
 25 27  1  0
 27 28  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA5276370

   ---

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: 378.44

Molecular Weight (Monoisotopic): 378.1804

AlogP: 1.51

#Rotatable Bonds: 6

Polar Surface Area: 96.77

Molecular Species: NEUTRAL

HBA: 7

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.03

CX Basic pKa: 8.20

CX LogP: 1.48

CX LogD: 0.71

Aromatic Rings: 3

Heavy Atoms: 28

QED Weighted: 0.65

Np Likeness Score: -1.15

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