N4-(1-benzylpiperidin-4-yl)-N2-(3-(dimethylamino)propyl)-6,7-dimethoxyquinazoline-2,4-diamine

ID: ALA1232432

PubChem CID: 46174171

Max Phase: Preclinical

Molecular Formula: C27H38N6O2

Molecular Weight: 478.64

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COc1cc2nc(NCCCN(C)C)nc(NC3CCN(Cc4ccccc4)CC3)c2cc1OC

Standard InChI:  InChI=1S/C27H38N6O2/c1-32(2)14-8-13-28-27-30-23-18-25(35-4)24(34-3)17-22(23)26(31-27)29-21-11-15-33(16-12-21)19-20-9-6-5-7-10-20/h5-7,9-10,17-18,21H,8,11-16,19H2,1-4H3,(H2,28,29,30,31)

Standard InChI Key:  YYFDMPHIONBOKZ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 35 38  0  0  0  0  0  0  0  0999 V2000
    0.5141   -0.2776    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.2285   -0.6901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2285   -1.5151    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.5141   -1.9276    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2004   -1.5151    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2004   -0.6901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5141   -2.7526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2004   -3.1651    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149   -2.7526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149   -1.9276    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6293   -3.1651    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2004   -3.9901    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149   -0.2776    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.9430   -0.2776    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6575   -0.6901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3720   -0.2776    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0864   -0.6901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8009   -0.2776    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.5154   -0.6901    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8009    0.5474    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149    0.5474    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6293    0.9599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6293    1.7849    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149    2.1974    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2004    1.7849    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2004    0.9599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149    3.0224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6293    3.4349    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6293    4.2599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3438    4.6724    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0583    4.2599    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0583    3.4349    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3438    3.0224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9149   -4.4026    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3438   -2.7526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  6  1  2  0
  2  1  1  0
  2  3  2  0
  2 14  1  0
  4  3  1  0
  4  7  2  0
  4  5  1  0
  5 10  2  0
  5  6  1  0
  6 13  1  0
  7  8  1  0
  8 12  1  0
  8  9  2  0
  9 11  1  0
  9 10  1  0
 35 11  1  0
 34 12  1  0
 21 13  1  0
 15 14  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 19 18  1  0
 20 18  1  0
 21 22  1  0
 21 26  1  0
 22 23  1  0
 23 24  1  0
 25 24  1  0
 27 24  1  0
 25 26  1  0
 27 28  1  0
 28 33  2  0
 28 29  1  0
 29 30  2  0
 30 31  1  0
 31 32  2  0
 32 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1232432

   N~4~-(1-Benzylpiperidin-4-Yl)-N~2~-[3-(Dimethylamino)propyl]-6,7-Dimethoxyquinazoline-2,4-Diamine

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: 478.64

Molecular Weight (Monoisotopic): 478.3056

AlogP: 4.09

#Rotatable Bonds: 11

Polar Surface Area: 74.78

Molecular Species: BASE

HBA: 8

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 9.48

CX LogP: 3.16

CX LogD: -0.39

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.40

Np Likeness Score: -1.22

References

1. Sundriyal S, Chen PB, Lubin AS, Lueg GA, Li F, White AJP, Malmquist NA, Vedadi M, Scherf A, Fuchter MJ..  (2017)  Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity.,  8  (5): [PMID:29308121] [10.1039/C7MD00052A]

2. Ma QS, Yao Y, Zheng YC, Feng S, Chang J, Yu B, Liu HM..  (2019)  Ligand-based design, synthesis and biological evaluation of xanthine derivatives as LSD1/KDM1A inhibitors.,  162  [PMID:30472603] [10.1016/j.ejmech.2018.11.035]

3. Mehndiratta, Samir, Liou, Jing-Ping.  (2020)  Histone lysine specific demethylase 1 inhibitors,  11  (9): [PMID:33479691] [10.1039/d0md00141d]

4. Menna M, Fiorentino F, Marrocco B, Lucidi A, Tomassi S, Cilli D, Romanenghi M, Cassandri M, Pomella S, Pezzella M, Del Bufalo D, Zeya Ansari MS, Tomašević N, Mladenović M, Viviano M, Sbardella G, Rota R, Trisciuoglio D, Minucci S, Mattevi A, Rotili D, Mai A..  (2022)  Novel non-covalent LSD1 inhibitors endowed with anticancer effects in leukemia and solid tumor cellular models.,  237  [PMID:35525212] [10.1016/j.ejmech.2022.114410]

5. Dai XJ, Liu Y, Xue LP, Xiong XP, Zhou Y, Zheng YC, Liu HM..  (2021)  Reversible Lysine Specific Demethylase 1 (LSD1) Inhibitors: A Promising Wrench to Impair LSD1.,  64  (5.0): [PMID:33619958] [10.1021/acs.jmedchem.0c02176]

6. Duan YC, Zhang SJ, Shi XJ, Jin LF, Yu T, Song Y, Guan YY..  (2021)  Research progress of dual inhibitors targeting crosstalk between histone epigenetic modulators for cancer therapy.,  222  [PMID:34107385] [10.1016/j.ejmech.2021.113588]

Source

Source(1):

• Scientific Literature