6-Methyl-biphenyl-3,4'-dicarboxylic acid 3-[(3-tert-butyl-phenyl)-amide] 4'-cyclopropylmethyl-amide

ID: ALA515466

PubChem CID: 44593646

Max Phase: Preclinical

Molecular Formula: C29H32N2O2

Molecular Weight: 440.59

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1ccc(C(=O)Nc2cccc(C(C)(C)C)c2)cc1-c1ccc(C(=O)NCC2CC2)cc1

Standard InChI:  InChI=1S/C29H32N2O2/c1-19-8-11-23(28(33)31-25-7-5-6-24(17-25)29(2,3)4)16-26(19)21-12-14-22(15-13-21)27(32)30-18-20-9-10-20/h5-8,11-17,20H,9-10,18H2,1-4H3,(H,30,32)(H,31,33)

Standard InChI Key:  GZGRGXPFYDFNHF-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 33 36  0  0  0  0  0  0  0  0999 V2000
   11.5729   -7.3621    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1562   -8.0771    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5656   -8.7923    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3953   -8.7959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8098   -8.0755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3940   -7.3613    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6349   -8.0734    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0477   -8.7872    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8720   -8.7855    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.2835   -8.0694    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8647   -7.3536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0418   -7.3589    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6249   -6.6469    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3313   -8.0741    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9214   -7.3579    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.9160   -8.7869    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.0910   -8.7838    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6757   -9.4967    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9606   -9.9105    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6735  -10.3258    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.2860   -9.4992    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8749  -10.2146    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.1110   -9.4974    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.5250  -10.2112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1117  -10.9229    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.5250  -11.6361    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.3509  -11.6348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7618  -10.9143    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.3462  -10.2041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1137  -12.3512    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6943  -13.0587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8261  -12.7673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.3998  -11.9374    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 14 16  1  0
  7  8  2  0
 16 17  1  0
 17 18  1  0
 19 18  1  0
 20 19  1  0
 18 20  1  0
  8  9  1  0
  4  5  1  0
  9 10  2  0
  9 21  1  0
  2  3  1  0
 21 22  2  0
 10 11  1  0
 21 23  1  0
  5  6  2  0
 23 24  1  0
 11 12  2  0
 24 25  2  0
 12  7  1  0
 25 26  1  0
  6  1  1  0
 26 27  2  0
 12 13  1  0
 27 28  1  0
  1  2  2  0
 28 29  2  0
 29 24  1  0
  2 14  1  0
 26 30  1  0
  5  7  1  0
 30 31  1  0
 14 15  2  0
 30 32  1  0
  3  4  2  0
 30 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA515466

   N3-(3-tert-butylphenyl)-N4''-(cyclopropylmethyl)-6-methylbiphenyl-3,4''-dicarboxamide

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: 440.59

Molecular Weight (Monoisotopic): 440.2464

AlogP: 6.35

#Rotatable Bonds: 6

Polar Surface Area: 58.20

Molecular Species: NEUTRAL

HBA: 2

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 6.63

CX LogD: 6.63

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.47

Np Likeness Score: -1.18

References

1. Angell RM, Angell TD, Bamborough P, Bamford MJ, Chung CW, Cockerill SG, Flack SS, Jones KL, Laine DI, Longstaff T, Ludbrook S, Pearson R, Smith KJ, Smee PA, Somers DO, Walker AL..  (2008)  Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes.,  18  (15): [PMID:18602262] [10.1016/j.bmcl.2008.06.028]

2. Bamborough P, Drewry D, Harper G, Smith GK, Schneider K..  (2008)  Assessment of chemical coverage of kinome space and its implications for kinase drug discovery.,  51  (24): [PMID:19035792] [10.1021/jm8011036]

3. McDermott, Ultan U and 24 more authors.  2007-12-11  Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.  [PMID:18077425]

4. Lafleur, Karine K, Huang, Danzhi D, Zhou, Ting T, Caflisch, Amedeo A and Nevado, Cristina C.  2009-10-22  Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4).  [PMID:19788238]

5. Incerti, Matteo M and 13 more authors.  2013-04-11  Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor.  [PMID:23489211]

6. Unzue, Andrea A and 6 more authors.  2014-08-14  Pyrrolo[3,2-b]quinoxaline derivatives as types I1/2 and II Eph tyrosine kinase inhibitors: structure-based design, synthesis, and in vivo validation.  [PMID:25076195]

7. Patwardhan, Parag P PP, Ivy, Kathryn S KS, Musi, Elgilda E, de Stanchina, Elisa E and Schwartz, Gary K GK.  2016-01-26  Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma.  [PMID:26675259]

8. Farag, Ahmed Karam AK and 5 more authors.  2017-12-01  Novel LCK/FMS inhibitors based on phenoxypyrimidine scaffold as potential treatment for inflammatory disorders.  [PMID:29107425]

Source

Source(1):

• Scientific Literature