N2-(1H-benzo[d]imidazol-5-yl)-N4-(5-cyclobutyl-1H-pyrazol-3-yl)quinazoline-2,4-diamine

ID: ALA3605055

Cas Number: 1644063-60-4

PubChem CID: 86346643

Max Phase: Preclinical

Molecular Formula: C22H20N8

Molecular Weight: 396.46

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  c1ccc2c(Nc3cc(C4CCC4)[nH]n3)nc(Nc3ccc4[nH]cnc4c3)nc2c1

Standard InChI:  InChI=1S/C22H20N8/c1-2-7-16-15(6-1)21(27-20-11-18(29-30-20)13-4-3-5-13)28-22(26-16)25-14-8-9-17-19(10-14)24-12-23-17/h1-2,6-13H,3-5H2,(H,23,24)(H3,25,26,27,28,29,30)

Standard InChI Key:  DLCOOKRUECVLCI-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 30 35  0  0  0  0  0  0  0  0999 V2000
   -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
   -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 N   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 N   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
    3.8942   -1.4964    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.1929   -0.7441    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5114   -1.4972    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4850    1.5292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1791    0.7520    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2995    2.9981    0.0000 N   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
    2.7434    5.2271    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2117    5.5338    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9571    4.2322    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.9496    3.1210    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.7861    0.7748    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7992   -0.7202    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2252   -1.1635    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.0899    0.0291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2042    1.2430    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.8268    6.9027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3876    8.2945    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8289    8.7098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2442    7.2684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  6  2  0
  5  4  2  0
  4  1  1  0
  5  6  1  0
  5 10  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  2  0
  8 11  1  0
 11 12  1  0
 12 13  2  0
 13 23  1  0
 22 14  1  0
 14 15  2  0
 15 12  1  0
 10 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  1  0
 21 17  2  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 22  1  0
 19 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3605055

   N~2~-(1h-Benzimidazol-6-Yl)-N~4~-(5-Cyclobutyl-1h-Pyrazol-3-Yl)quinazoline-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: 396.46

Molecular Weight (Monoisotopic): 396.1811

AlogP: 4.98

#Rotatable Bonds: 5

Polar Surface Area: 107.20

Molecular Species: NEUTRAL

HBA: 6

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.32

CX Basic pKa: 6.68

CX LogP: 4.83

CX LogD: 4.76

Aromatic Rings: 5

Heavy Atoms: 30

QED Weighted: 0.33

Np Likeness Score: -1.50

References

1. Lazarus MB, Shokat KM..  (2015)  Discovery and structure of a new inhibitor scaffold of the autophagy initiating kinase ULK1.,  23  (17): [PMID:26275681] [10.1016/j.bmc.2015.07.034]

2. Zhang L, Ouyang L, Guo Y, Zhang J, Liu B..  (2018)  UNC-51-like Kinase 1: From an Autophagic Initiator to Multifunctional Drug Target.,  61  (15): [PMID:29509411] [10.1021/acs.jmedchem.7b01684]

3. Sun D,Yang Z,Zhen Y,Yang Y,Chen Y,Yuan Y,Zhang L,Zeng X,Chen L.  (2020)  Discovery of 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives as novel ULK1 inhibitors that block autophagy and induce apoptosis in non-small cell lung cancer.,  208  [PMID:32961380] [10.1016/j.ejmech.2020.112782]

4. Ye W, Fan C, Fu K, Wang X, Lin J, Nian S, Liu C, Zhou W..  (2022)  The SAR and action mechanisms of autophagy inhibitors that eliminate drug resistance.,  244  [PMID:36283182] [10.1016/j.ejmech.2022.114846]

Source

Source(1):

• Scientific Literature