4-[(2S)-6-(2-chloro-5-methylpyrimidin-4-yl)-2-methyl-1,2,3,4-tetrahdronaphthalene-1-carbonyl]benzene-1,3-diol

ID: ALA3715044

PubChem CID: 117967623

Max Phase: Preclinical

Molecular Formula: C23H21ClN2O3

Molecular Weight: 408.89

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cnc(Cl)nc1-c1ccc2c(c1)CC[C@H](C)C2C(=O)c1ccc(O)cc1O

Standard InChI:  InChI=1S/C23H21ClN2O3/c1-12-3-4-14-9-15(21-13(2)11-25-23(24)26-21)5-7-17(14)20(12)22(29)18-8-6-16(27)10-19(18)28/h5-12,20,27-28H,3-4H2,1-2H3/t12-,20?/m0/s1

Standard InChI Key:  GXMWDEYADMNXAV-SVZXGPMESA-N

Molfile:  

     RDKit          2D

 29 32  0  0  0  0  0  0  0  0999 V2000
    5.2037   -5.2377    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9072   -5.9922    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6056   -5.2467    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6003   -3.7467    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8969   -2.9922    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1985   -3.7377    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5685   -5.8503    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.2450   -5.8341    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.2995   -2.9981    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2613   -3.5999    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 C   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 C   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 C   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
    3.6321   -1.3486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9086    1.5029    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8985    3.0030    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1925    3.7616    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.4965    3.0203    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -6.5065    1.5203    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2125    0.7617    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2206   -0.4383    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1845    4.9616    0.0000 Cl  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  5  1  0
  5  6  2  0
  6  1  1  0
  3  7  1  0
  1  8  1  0
  4  9  1  0
  9 17  1  0
  9 10  2  0
 15 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  2  0
 14 16  1  0
 15 16  2  0
 15 20  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 18 21  1  6
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 22  1  0
 12 22  1  0
 27 28  1  0
 24 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3715044

   [(2S)-6-(2-chloro-5-methylpyrimidin-4-yl)-2-methyl-1,2,3,4-tetrahydronaphthalen-1-yl]-(2,4-dihydroxyphenyl)methanone

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: 408.89

Molecular Weight (Monoisotopic): 408.1241

AlogP: 5.07

#Rotatable Bonds: 3

Polar Surface Area: 83.31

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 7.84

CX Basic pKa: 0.27

CX LogP: 6.26

CX LogD: 6.13

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.47

Np Likeness Score: 0.17

References

1.  (2015)  Tetrahydroisoquinoline compounds and their use as pyruvate dehydrogenase kinase inhibitors, 

2. Morrell, J A JA and 5 more authors.  2003-12  AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2.  [PMID:14641019]

3. Moore, Jonathan D and 12 more authors.  2014-12-30  VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells.  [PMID:25404640]

4. Tso, Shih-Chia and 9 more authors.  2017-02-09  Development of Dihydroxyphenyl Sulfonylisoindoline Derivatives as Liver-Targeting Pyruvate Dehydrogenase Kinase Inhibitors.  [PMID:28085286]

Source

Source(1):

• Patent Bioactivity Data