N-[4-(2-chloro-5-methylpyrimidin-4-yl)phenyl]-N-({4-[(3,3-difluoropyrrolidin-1-yl)methyl]phenyl}methyl)-2,4-dihydroxybenzamide

ID: ALA3730188

PubChem CID: 117967688

Max Phase: Preclinical

Molecular Formula: C30H27ClF2N4O3

Molecular Weight: 565.02

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cnc(Cl)nc1-c1ccc(N(Cc2ccc(CN3CCC(F)(F)C3)cc2)C(=O)c2ccc(O)cc2O)cc1

Standard InChI:  InChI=1S/C30H27ClF2N4O3/c1-19-15-34-29(31)35-27(19)22-6-8-23(9-7-22)37(28(40)25-11-10-24(38)14-26(25)39)17-21-4-2-20(3-5-21)16-36-13-12-30(32,33)18-36/h2-11,14-15,38-39H,12-13,16-18H2,1H3

Standard InChI Key:  NDZDDEMSENNYBA-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 40 44  0  0  0  0  0  0  0  0999 V2000
    1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3383   -1.3500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    2.7000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6003    1.4977    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6024    2.6977    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8990    0.7455    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2003    1.4932    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.4990    0.7409    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8964   -0.7553    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1931   -1.5094    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1885   -3.0094    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8871   -3.7554    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5904   -3.0014    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5951   -1.5014    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.8007    1.4864    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.0971    0.7319    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.0919   -0.7681    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7903   -1.5136    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.4939   -0.7591    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8824   -5.2561    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  -10.3875   -1.5257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5799   -6.0002    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5728   -7.5001    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8683   -8.2562    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1709   -7.5123    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1779   -6.0123    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2200   -5.4173    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5308   -8.0953    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
  -10.3802   -3.0265    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  -11.5877   -3.8947    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  -11.1143   -5.3181    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.6143   -5.3077    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.1607   -3.8779    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  -12.3067   -5.1830    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  -10.6025   -6.4034    0.0000 F   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
  1  7  1  0
  3  8  1  0
  4  9  1  0
  9 10  2  0
  9 11  1  0
 11 12  1  0
 12 13  1  0
 11 14  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 14  1  0
 13 20  2  0
 20 21  1  0
 21 22  2  0
 22 23  1  0
 23 24  2  0
 24 13  1  0
 17 25  1  0
 22 26  1  0
 25 27  2  0
 27 28  1  0
 28 29  2  0
 29 30  1  0
 30 31  2  0
 31 25  1  0
 31 32  1  0
 28 33  1  0
 26 34  1  0
 34 35  1  0
 35 36  1  0
 36 37  1  0
 37 38  1  0
 38 34  1  0
 36 39  1  0
 36 40  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3730188

   N-[4-(2-chloro-5-methylpyrimidin-4-yl)phenyl]-N-[[4-[(3,3-difluoropyrrolidin-1-yl)methyl]phenyl]methyl]-2,4-dihydroxybenzamide

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: 565.02

Molecular Weight (Monoisotopic): 564.1740

AlogP: 6.20

#Rotatable Bonds: 7

Polar Surface Area: 89.79

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 7.83

CX Basic pKa: 5.67

CX LogP: 6.32

CX LogD: 6.17

Aromatic Rings: 4

Heavy Atoms: 40

QED Weighted: 0.26

Np Likeness Score: -1.03

References

1.  (2015)  Resorcinol n-aryl amide compounds, for 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. Meng, Tao T and 10 more authors.  2014-12-11  Discovery and optimization of 4,5-diarylisoxazoles as potent dual inhibitors of pyruvate dehydrogenase kinase and heat shock protein 90.  [PMID:25383915]

4. 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]

5. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]

Source

Source(1):

• Patent Bioactivity Data