(S)-2-(1-(1-(ethylsulfonyl)pyrrolidin-3-yl)-1H-pyrazol-4-yloxy)pyrido[3,4-d]pyrimidin-4-ol

ID: ALA3787044

PubChem CID: 136048748

Max Phase: Preclinical

Molecular Formula: C16H18N6O4S

Molecular Weight: 390.43

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CCS(=O)(=O)N1CC[C@H](n2cc(Oc3nc(O)c4ccncc4n3)cn2)C1

Standard InChI:  InChI=1S/C16H18N6O4S/c1-2-27(24,25)21-6-4-11(9-21)22-10-12(7-18-22)26-16-19-14-8-17-5-3-13(14)15(23)20-16/h3,5,7-8,10-11H,2,4,6,9H2,1H3,(H,19,20,23)/t11-/m0/s1

Standard InChI Key:  DQKJPEFRHKBNRV-NSHDSACASA-N

Molfile:  

     RDKit          2D

 27 30  0  0  0  0  0  0  0  0999 V2000
   13.6032   -1.6376    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.4962   -2.1008    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   13.4509   -2.8278    0.0000 O   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
   -2.6111    0.7486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6111   -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
    0.0000    0.7486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    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
    9.0393   -0.3939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8678   -1.6233    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3046   -1.1926    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3390    0.3070    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9235    0.8031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3061   -3.5895    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2605   -4.3170    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  2  2  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  9  1  0
  8  4  1  0
  8  9  2  0
  8 13  1  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 11 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  1  0
 19 20  2  0
 20 16  1  0
 21 18  1  1
 21 22  1  0
 22 23  1  0
 23 24  1  0
 24 25  1  0
 25 21  1  0
 23  2  1  0
  2 26  1  0
 26 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3787044

   ---

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: 390.43

Molecular Weight (Monoisotopic): 390.1110

AlogP: 1.32

#Rotatable Bonds: 5

Polar Surface Area: 123.33

Molecular Species: NEUTRAL

HBA: 9

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.16

CX Basic pKa: 3.37

CX LogP: 0.30

CX LogD: 0.30

Aromatic Rings: 3

Heavy Atoms: 27

QED Weighted: 0.69

Np Likeness Score: -1.54

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