(R)-2-(1-(1-benzylpiperidin-3-yl)-1H-pyrazol-4-yloxy)pyrido[3,4-d]pyrimidin-4-ol

ID: ALA3785404

PubChem CID: 136048749

Max Phase: Preclinical

Molecular Formula: C22H22N6O2

Molecular Weight: 402.46

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Oc1nc(Oc2cnn([C@@H]3CCCN(Cc4ccccc4)C3)c2)nc2cnccc12

Standard InChI:  InChI=1S/C22H22N6O2/c29-21-19-8-9-23-12-20(19)25-22(26-21)30-18-11-24-28(15-18)17-7-4-10-27(14-17)13-16-5-2-1-3-6-16/h1-3,5-6,8-9,11-12,15,17H,4,7,10,13-14H2,(H,25,26,29)/t17-/m1/s1

Standard InChI Key:  CCZFELUQXWMJLX-QGZVFWFLSA-N

Molfile:  

     RDKit          2D

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   -1.2964   -1.4973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    0.0000   -0.7486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2964   -1.4973    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.5929   -0.7486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5929    0.7486    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.2964    1.4973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2964    2.6973    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.8942   -1.4964    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.1929   -0.7441    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5464   -1.3604    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5462   -0.2422    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.7917    1.0542    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.3256    0.7372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   12.0351   -0.4677    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3190    0.8503    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8195    0.8892    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9709   -3.0642    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4713   -3.1010    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1920   -4.4165    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6916   -4.4502    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4706   -3.1683    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7500   -1.8528    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2503   -1.8191    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
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 18 15  1  6
 18 19  1  0
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 19 20  1  0
 20 21  1  0
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 20 24  1  0
 24 25  1  0
 25 26  2  0
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 29 30  2  0
 30 25  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3785404

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 402.46

Molecular Weight (Monoisotopic): 402.1804

AlogP: 3.56

#Rotatable Bonds: 5

Polar Surface Area: 89.19

Molecular Species: NEUTRAL

HBA: 8

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.17

CX Basic pKa: 8.24

CX LogP: 3.31

CX LogD: 2.41

Aromatic Rings: 4

Heavy Atoms: 30

QED Weighted: 0.55

Np Likeness Score: -1.22

References

1. McAllister TE, England KS, Hopkinson RJ, Brennan PE, Kawamura A, Schofield CJ..  (2016)  Recent Progress in Histone Demethylase Inhibitors.,  59  (4): [PMID:26710088] [10.1021/acs.jmedchem.5b01758]

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. England, Katherine S and 12 more authors.  2014-12-01  Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.  [PMID:26682034]

4. Korczynska, Magdalena M and 14 more authors.  2016-02-25  Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors.  [PMID:26699912]

5. Labadie, Sharada S SS and 19 more authors.  2016-09-15  Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.  [PMID:27499454]

6. Horton, John R and 21 more authors.  2018-04-12  Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A.  [PMID:29537847]

7. Horton, John R and 22 more authors.  2018-12-13  Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A.  [PMID:30392349]

8. Jaikhan, Pattaporn P and 5 more authors.  2019-05-15  Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors.  [PMID:30928196]

9. 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