N-(2-(4-(3-cyano-6-isopropyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-5-yl)phenoxy)ethyl)acrylamide

ID: ALA5290962

Max Phase: Preclinical

Molecular Formula: C21H21N5O3

Molecular Weight: 391.43

Names and Identifiers

Canonical SMILES:  C=CC(=O)NCCOc1ccc(-c2[nH]c3c(C#N)cnn3c(=O)c2C(C)C)cc1

Standard InChI:  InChI=1S/C21H21N5O3/c1-4-17(27)23-9-10-29-16-7-5-14(6-8-16)19-18(13(2)3)21(28)26-20(25-19)15(11-22)12-24-26/h4-8,12-13,25H,1,9-10H2,2-3H3,(H,23,27)

Standard InChI Key:  GAWCCMHWAMQURK-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 29 31  0  0  0  0  0  0  0  0999 V2000
   -4.8587   -1.6447    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6452   -0.8478    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4317   -0.0509    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9166    0.6166    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4316    1.2843    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6468    1.0292    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6468    0.2039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9332   -0.2024    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2259    0.2076    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2259    1.0296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9350    1.4399    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9350    2.2650    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5114    1.4421    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5114    2.2672    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7969    1.0296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5114   -0.2048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7967    0.2075    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0847   -0.2044    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0847   -1.0296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7949   -1.4415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5114   -1.0333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6296   -1.4421    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3441   -1.0296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0587   -1.4421    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7732   -1.0296    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.4877   -1.4421    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2021   -1.0296    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4877   -2.2672    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.9166   -1.4421    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  3  0
  3  2  1  0
  3  4  1  0
  4  5  2  0
  6  5  1  0
  6  7  1  0
  7  3  2  0
  7  8  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11  6  1  0
 11 12  2  0
 10 13  1  0
 13 14  1  0
 13 15  1  0
 16  9  1  0
 17 16  2  0
 18 17  1  0
 19 18  2  0
 20 19  1  0
 16 21  1  0
 21 20  2  0
 19 22  1  0
 22 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 26 28  2  0
 27 29  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA5290962

   ---

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: 391.43

Molecular Weight (Monoisotopic): 391.1644

AlogP: 2.37

#Rotatable Bonds: 7

Polar Surface Area: 112.28

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.63

CX Basic pKa: ┄

CX LogP: 2.01

CX LogD: 2.01

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.47

Np Likeness Score: -0.95

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