1-(4-chlorophenyl)-N-(2-methyl-2-morpholinopropyl)-3-phenyl-1H-pyrazole-4-carboxamide

ID: ALA4790440

PubChem CID: 141766240

Max Phase: Preclinical

Molecular Formula: C24H27ClN4O2

Molecular Weight: 438.96

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(C)(CNC(=O)c1cn(-c2ccc(Cl)cc2)nc1-c1ccccc1)N1CCOCC1

Standard InChI:  InChI=1S/C24H27ClN4O2/c1-24(2,28-12-14-31-15-13-28)17-26-23(30)21-16-29(20-10-8-19(25)9-11-20)27-22(21)18-6-4-3-5-7-18/h3-11,16H,12-15,17H2,1-2H3,(H,26,30)

Standard InChI Key:  PTOBDOLLYDMPSN-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 31 34  0  0  0  0  0  0  0  0999 V2000
   31.8746  -12.4642    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.2873  -13.1741    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.6957  -12.4617    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.7206  -13.5782    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.4592  -13.2285    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.3567  -12.4177    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.5512  -12.2656    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.1621  -12.9832    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   30.1757  -13.6214    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.1938  -14.4384    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   30.8742  -13.1973    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.2008  -11.5280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.6663  -10.8550    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3162  -10.1174    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.5008  -10.0517    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0367  -10.7295    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.3894  -11.4643    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.5697  -14.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.7967  -14.6482    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6442  -15.4502    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.2637  -15.9845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.0383  -15.7111    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.1871  -14.9097    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.5909  -13.5956    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.1490   -9.3141    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   33.0039  -13.5686    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   33.0155  -14.3840    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.7271  -14.7784    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.4290  -14.3591    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.4146  -13.5411    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.6983  -13.1423    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  0
  4  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  8  4  2  0
  5  9  1  0
  9 10  2  0
  9 11  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 12  1  0
  7 12  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 18  1  0
  4 18  1  0
 11 24  1  0
 15 25  1  0
  2 24  1  0
  2 26  1  0
 26 27  1  0
 26 31  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4790440

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 438.96

Molecular Weight (Monoisotopic): 438.1823

AlogP: 4.03

#Rotatable Bonds: 6

Polar Surface Area: 59.39

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.79

CX Basic pKa: 6.63

CX LogP: 4.27

CX LogD: 4.20

Aromatic Rings: 3

Heavy Atoms: 31

QED Weighted: 0.63

Np Likeness Score: -2.12

References

1. Zhao B,Liang Q,Ren H,Zhang X,Wu Y,Zhang K,Ma LY,Zheng YC,Liu HM.  (2020)  Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B).,  192  [PMID:32155529] [10.1016/j.ejmech.2020.112161]

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