N-(2-(2-chlorophenyl)-2-morpholinoethyl)-3-isopropyl-1H-pyrazole-5-carboxamide

ID: ALA5273968

Max Phase: Preclinical

Molecular Formula: C19H25ClN4O2

Molecular Weight: 376.89

Names and Identifiers

Canonical SMILES:  CC(C)c1cc(C(=O)NCC(c2ccccc2Cl)N2CCOCC2)[nH]n1

Standard InChI:  InChI=1S/C19H25ClN4O2/c1-13(2)16-11-17(23-22-16)19(25)21-12-18(24-7-9-26-10-8-24)14-5-3-4-6-15(14)20/h3-6,11,13,18H,7-10,12H2,1-2H3,(H,21,25)(H,22,23)

Standard InChI Key:  YPOZVBBSPPQEEN-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 26 28  0  0  0  0  0  0  0  0999 V2000
   -2.5063   -0.2570    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7536   -1.0441    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0825   -1.5387    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4253   -1.0654    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6768   -0.2570    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6243   -1.2801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0378   -0.6937    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7631   -0.9083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3495   -0.3219    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1506   -0.5365    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7372    0.0496    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5356   -0.1650    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7503   -0.9662    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1679   -1.5509    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3661   -1.3410    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5226    0.8507    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.1349    0.4791    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3338    0.6937    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1192    1.4947    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7056    2.0811    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.5067    1.8665    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7213    1.0655    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4096   -2.0811    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9210    0.4611    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7503    0.4611    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5063    1.1793    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  4  3  1  0
  5  4  2  0
  1  5  1  0
  4  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 11 10  2  0
 12 11  1  0
 13 12  2  0
 14 13  1  0
 15 14  2  0
 10 15  1  0
 11 16  1  0
  9 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
  6 23  2  0
  1 24  1  0
 24 25  1  0
 24 26  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5273968

   ---

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: 376.89

Molecular Weight (Monoisotopic): 376.1666

AlogP: 2.99

#Rotatable Bonds: 6

Polar Surface Area: 70.25

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.60

CX Basic pKa: 5.05

CX LogP: 2.84

CX LogD: 2.83

Aromatic Rings: 2

Heavy Atoms: 26

QED Weighted: 0.81

Np Likeness Score: -1.99

References

1. Yang GJ, Wu J, Miao L, Zhu MH, Zhou QJ, Lu XJ, Lu JF, Leung CH, Ma DL, Chen J..  (2021)  Pharmacological inhibition of KDM5A for cancer treatment.,  226  [PMID:34555614] [10.1016/j.ejmech.2021.113855]

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