8-(1-methyl-1H-imidazol-4-yl)-2-(4,4,4-trifluorobutoxy)pyrido[3,4-d]pyrimidin-4-ol

ID: ALA3787534

PubChem CID: 136959977

Max Phase: Preclinical

Molecular Formula: C15H14F3N5O2

Molecular Weight: 353.30

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cn1cnc(-c2nccc3c(O)nc(OCCCC(F)(F)F)nc23)c1

Standard InChI:  InChI=1S/C15H14F3N5O2/c1-23-7-10(20-8-23)12-11-9(3-5-19-12)13(24)22-14(21-11)25-6-2-4-15(16,17)18/h3,5,7-8H,2,4,6H2,1H3,(H,21,22,24)

Standard InChI Key:  GVIVKUKLHYWHES-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 25 27  0  0  0  0  0  0  0  0999 V2000
   -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
    6.4942   -1.4919    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7928   -0.7396    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0941   -1.4873    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1325   -0.8858    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    9.0962   -2.6873    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.1343   -2.0857    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2919   -2.9980    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0752   -3.8536    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5336   -5.2819    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0336   -5.2872    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5022   -3.8623    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7354   -6.2606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  6  1  0
  5  1  1  0
  5  6  2  0
  5 10  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
  8 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 16 18  1  0
 16 19  1  0
  4 20  1  0
 20 21  1  0
 21 22  2  0
 22 23  1  0
 23 24  1  0
 24 20  2  0
 23 25  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3787534

   ---

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: 353.30

Molecular Weight (Monoisotopic): 353.1100

AlogP: 2.85

#Rotatable Bonds: 5

Polar Surface Area: 85.95

Molecular Species: NEUTRAL

HBA: 7

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.50

CX Basic pKa: 2.95

CX LogP: 3.06

CX LogD: 3.06

Aromatic Rings: 3

Heavy Atoms: 25

QED Weighted: 0.71

Np Likeness Score: -0.88

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