4-((3-((4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-6-methoxy-2-methylquinazolin-7-yl)oxy)propyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

ID: ALA5277122

Max Phase: Preclinical

Molecular Formula: C35H34F3N7O6

Molecular Weight: 705.69

Names and Identifiers

Canonical SMILES:  COc1cc2c(N[C@H](C)c3cc(N)cc(C(F)(F)F)c3)nc(C)nc2cc1OCCCNc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Standard InChI:  InChI=1S/C35H34F3N7O6/c1-17(19-12-20(35(36,37)38)14-21(39)13-19)41-31-23-15-27(50-3)28(16-25(23)42-18(2)43-31)51-11-5-10-40-24-7-4-6-22-30(24)34(49)45(33(22)48)26-8-9-29(46)44-32(26)47/h4,6-7,12-17,26,40H,5,8-11,39H2,1-3H3,(H,41,42,43)(H,44,46,47)/t17-,26?/m1/s1

Standard InChI Key:  LMBPERMEYQBSHS-SIHBAMTISA-N

Molfile:  

 
     RDKit          2D

 51 56  0  0  0  0  0  0  0  0999 V2000
   -5.0015    2.2671    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2868    1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2868    1.0304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5724    0.6183    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8579    1.0304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8579    1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5724    2.2671    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1434    2.2671    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1434    3.0915    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4289    2.6793    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4289    1.8548    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5724   -0.2060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2868   -0.6182    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8579   -0.6182    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8579   -1.4427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5724   -1.8548    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5724   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2868   -3.0915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8579   -3.0915    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1434   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1434   -1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4289   -1.4427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7145   -1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7145   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -3.0915    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4289   -3.0915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8579   -3.0915    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.5724   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2868   -3.0915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0015   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0015   -1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2868   -1.4427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5724   -1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9678   -1.3052    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1709   -1.4976    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2976   -0.5632    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.1220   -0.6457    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6716   -0.0411    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8854    0.1510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0609    0.1510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6488    0.8655    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0609    1.5801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8854    1.5801    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.2976    0.8655    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1220    0.8655    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.6488    2.2946    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4289   -3.0915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.4427    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -1.8548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  2  7  2  0
  7  6  1  0
  6  8  1  0
  8  9  1  0
  8 10  1  0
  8 11  1  0
  4 12  1  0
 12 13  1  6
 12 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 17 19  1  0
 20 19  2  0
 15 21  2  0
 21 20  1  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  2  0
 32 33  1  0
 33 34  2  0
 30 35  2  0
 35 34  1  0
 35 36  1  0
 36 37  2  0
 36 38  1  0
 34 39  1  0
 39 38  1  0
 39 40  2  0
 38 41  1  0
 41 42  1  0
 42 43  1  0
 43 44  1  0
 45 44  1  0
 41 46  1  0
 46 45  1  0
 46 47  2  0
 44 48  2  0
 20 49  1  0
 24 49  2  0
 23 50  1  0
 50 51  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5277122

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 705.69

Molecular Weight (Monoisotopic): 705.2523

AlogP: 5.00

#Rotatable Bonds: 11

Polar Surface Area: 177.87

Molecular Species: NEUTRAL

HBA: 11

HBD: 4

#RO5 Violations: 3

HBA (Lipinski): 13

HBD (Lipinski): 5

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 11.59

CX Basic pKa: 6.83

CX LogP: 3.92

CX LogD: 3.88

Aromatic Rings: 4

Heavy Atoms: 51

QED Weighted: 0.09

Np Likeness Score: -0.90

References

1. Bian Y, Alem D, Beato F, Hogenson TL, Yang X, Jiang K, Cai J, Ma WW, Fernandez-Zapico M, Tan AC, Lawrence NJ, Fleming JB, Yuan Y, Xie H..  (2022)  Development of SOS1 Inhibitor-Based Degraders to Target KRAS-Mutant Colorectal Cancer.,  65  (24.0): [PMID:36459180] [10.1021/acs.jmedchem.2c01300]

Source

Source(1):

• Scientific Literature