3-(4-Methoxy-phenyl)-1-[2-(2-methyl-1H-indol-3-yl)-ethyl]-1-pyridin-4-ylmethyl-thiourea

ID: ALA193891

PubChem CID: 2157766

Max Phase: Preclinical

Molecular Formula: C25H26N4OS

Molecular Weight: 430.58

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COc1ccc(NC(=S)N(CCc2c(C)[nH]c3ccccc23)Cc2ccncc2)cc1

Standard InChI:  InChI=1S/C25H26N4OS/c1-18-22(23-5-3-4-6-24(23)27-18)13-16-29(17-19-11-14-26-15-12-19)25(31)28-20-7-9-21(30-2)10-8-20/h3-12,14-15,27H,13,16-17H2,1-2H3,(H,28,31)

Standard InChI Key:  QQJRJLBTZMZXDB-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 31 34  0  0  0  0  0  0  0  0999 V2000
    3.1417   -1.1667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1417    0.1708    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.6292   -0.5042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2667   -3.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3542   -0.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3542   -0.0917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4625   -2.9125    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.8167   -2.4667    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.4000   -1.9542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5250   -3.8667    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    4.2042   -2.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9042   -3.5250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4917   -3.0125    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.6250   -2.6417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2375   -2.9792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1000   -3.3542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4542   -0.5042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.8792   -3.4250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1750   -2.0292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9792   -2.1917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6875   -3.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6417   -1.3292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0417   -3.1542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.6417    0.3208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7500   -3.8000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0417   -2.4000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5542   -3.9667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8500   -2.5667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5917   -2.5417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9292   -0.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9292   -0.0917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  1  0
  3  1  2  0
  4  7  1  0
  5  1  1  0
  6  5  1  0
  7 11  1  0
  8  4  1  0
  9  1  1  0
 10  4  2  0
 11  9  1  0
 12  7  1  0
 13 26  2  0
 14  8  1  0
 15 20  1  0
 16 12  1  0
 17  3  1  0
 18 14  2  0
 19 14  1  0
 20 19  2  0
 21 18  1  0
 22  5  2  0
 23 15  1  0
 24  6  2  0
 25 27  2  0
 26 28  1  0
 27 16  1  0
 28 16  2  0
 29 23  1  0
 30 22  1  0
 31 30  2  0
  6  2  1  0
 31 24  1  0
 13 25  1  0
 15 21  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA193891

   1-(4-Methoxyphenyl)-3-[2-(2-methyl-1H-indol-3-YL)ethyl]-3-[(pyridin-4-YL)methyl]thiourea

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: 430.58

Molecular Weight (Monoisotopic): 430.1827

AlogP: 5.32

#Rotatable Bonds: 7

Polar Surface Area: 53.18

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 5.02

CX LogP: 4.88

CX LogD: 4.87

Aromatic Rings: 4

Heavy Atoms: 31

QED Weighted: 0.39

Np Likeness Score: -1.42

References

1. Toledo-Sherman L, Deretey E, Slon-Usakiewicz JJ, Ng W, Dai JR, Foster JE, Redden PR, Uger MD, Liao LC, Pasternak A, Reid N..  (2005)  Frontal affinity chromatography with MS detection of EphB2 tyrosine kinase receptor. 2. Identification of small-molecule inhibitors via coupling with virtual screening.,  48  (9): [PMID:15857128] [10.1021/jm0492204]

2. Remsing Rix, L L LL and 11 more authors.  2009-03  Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells.  [PMID:19039322]

3. 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]

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

5. Zhang, Chun-Hui CH and 17 more authors.  2015-05-14  Design, Synthesis, and Structure-Activity Relationship Studies of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as a New Class of Src Inhibitors with Potent Activities in Models of Triple Negative Breast Cancer.  [PMID:25835317]

6. Lodola, Alessio A, Giorgio, Carmine C, Incerti, Matteo M, Zanotti, Ilaria I and Tognolini, Massimiliano M.  2017-12-15  Targeting Eph/ephrin system in cancer therapy.  [PMID:28780190]

7. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

8. Wang, Zhen and 17 more authors.  2018-09-13  Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2.  [PMID:30075624]

Source

Source(1):

• Scientific Literature