5-(1-(1-(2-chloroacetyl)piperidin-4-yl)-1H-pyrazol-4-yl)-6-isopropyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile

ID: ALA5269187

Max Phase: Preclinical

Molecular Formula: C20H22ClN7O2

Molecular Weight: 427.90

Names and Identifiers

Canonical SMILES:  CC(C)c1c(-c2cnn(C3CCN(C(=O)CCl)CC3)c2)[nH]c2c(C#N)cnn2c1=O

Standard InChI:  InChI=1S/C20H22ClN7O2/c1-12(2)17-18(25-19-13(8-22)9-24-28(19)20(17)30)14-10-23-27(11-14)15-3-5-26(6-4-15)16(29)7-21/h9-12,15,25H,3-7H2,1-2H3

Standard InChI Key:  UFTLGLOWZBFFND-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

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   -2.6527    1.1332    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9408    0.7213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9408   -0.1038    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6509   -0.5157    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3673   -0.1075    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1552   -0.3635    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6421    0.3067    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1551    0.9768    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3695   -1.1635    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5839   -1.9636    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2235   -0.5180    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4673   -0.1812    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0866   -0.7965    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3272   -1.5134    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1370   -1.3413    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9149   -0.7965    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3290   -0.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1573   -0.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5714   -0.7965    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1573   -1.5138    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3290   -1.5137    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3997   -0.7965    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8138   -0.0792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.8138   -1.5138    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6421   -1.5138    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -1.2235    1.1354    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2235    1.9636    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5062    0.7213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6527    1.9614    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  0
  4  3  2  0
  5  4  1  0
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  7 10  1  0
 10 11  3  0
  4 12  1  0
 13 12  2  0
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 14 15  1  0
 15 16  2  0
 16 12  1  0
 14 17  1  0
 18 17  1  0
 19 18  1  0
 20 19  1  0
 21 20  1  0
 22 21  1  0
 17 22  1  0
 20 23  1  0
 23 24  2  0
 23 25  1  0
 25 26  1  0
  3 27  1  0
 27 28  1  0
 27 29  1  0
  2 30  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA5269187

   ---

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: 427.90

Molecular Weight (Monoisotopic): 427.1524

AlogP: 2.28

#Rotatable Bonds: 4

Polar Surface Area: 112.08

Molecular Species: NEUTRAL

HBA: 7

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.41

CX Basic pKa: 1.96

CX LogP: 0.61

CX LogD: 0.61

Aromatic Rings: 3

Heavy Atoms: 30

QED Weighted: 0.64

Np Likeness Score: -1.25

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