N-((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)-7-methoxy-2-methyl-6-((S)-tetrahydrofuran-3-yloxy)quinazolin-4-amine

ID: ALA4519023

PubChem CID: 138911318

Product Number: B422682, Order Now?

Max Phase: Preclinical

Molecular Formula: C23H25F3N4O3

Molecular Weight: 462.47

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  COc1cc2nc(C)nc(N[C@H](C)c3cc(N)cc(C(F)(F)F)c3)c2cc1O[C@H]1CCOC1

Standard InChI:  InChI=1S/C23H25F3N4O3/c1-12(14-6-15(23(24,25)26)8-16(27)7-14)28-22-18-9-21(33-17-4-5-32-11-17)20(31-3)10-19(18)29-13(2)30-22/h6-10,12,17H,4-5,11,27H2,1-3H3,(H,28,29,30)/t12-,17+/m1/s1

Standard InChI Key:  XVFDNRYZXDHTHT-PXAZEXFGSA-N

Molfile:  

 
     RDKit          2D

 33 36  0  0  0  0  0  0  0  0999 V2000
    7.9518   -3.4049    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9506   -4.2245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6587   -4.6334    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3683   -4.2240    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3655   -3.4013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6569   -2.9961    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6585   -5.4506    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9506   -5.8590    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3661   -5.8594    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.3659   -6.6766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6576   -7.0807    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.6571   -7.8971    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3652   -8.3067    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.9491   -8.3052    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0724   -7.0788    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0720   -7.8936    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7763   -8.2995    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4814   -7.8919    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.4779   -7.0740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.7731   -6.6717    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1837   -6.6621    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.1799   -5.8449    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1901   -8.2987    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.8378   -5.3612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5817   -4.5851    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.7644   -4.5889    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5157   -5.3673    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2439   -2.9965    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2437   -2.1793    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    6.5363   -3.4053    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    6.5334   -2.5878    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.0716   -2.9901    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.1921   -9.1159    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  1  0
  3  7  1  0
  7  8  1  6
  7  9  1  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 16  1  0
 15 10  1  0
 12 14  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 15  2  0
 19 21  1  0
 22 21  1  1
 18 23  1  0
 22 24  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 22  1  0
  1 28  1  0
 28 29  1  0
 28 30  1  0
 28 31  1  0
  5 32  1  0
 23 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4519023

   BI-3406

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: Yes

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 462.47

Molecular Weight (Monoisotopic): 462.1879

AlogP: 4.89

#Rotatable Bonds: 6

Polar Surface Area: 91.52

Molecular Species: NEUTRAL

HBA: 7

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 6.40

CX LogP: 3.81

CX LogD: 3.77

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.50

Np Likeness Score: -0.77

References

1.  (2018)  Novel benzylamino substituted quinazolines and derivatives as sos1 inhibitors, 

2. Ramharter J, Kessler D, Ettmayer P, Hofmann MH, Gerstberger T, Gmachl M, Wunberg T, Kofink C, Sanderson M, Arnhof H, Bader G, Rumpel K, Zöphel A, Schnitzer R, Böttcher J, O'Connell JC, Mendes RL, Richard D, Pototschnig N, Weiner I, Hela W, Hauer K, Haering D, Lamarre L, Wolkerstorfer B, Salamon C, Werni P, Munico-Martinez S, Meyer R, Kennedy MD, Kraut N, McConnell DB..  (2021)  One Atom Makes All the Difference: Getting a Foot in the Door between SOS1 and KRAS.,  64  (10.0): [PMID:33719426] [10.1021/acs.jmedchem.0c01949]

3. Liu M, Zhou G, Su W, Gu Y, Gao M, Wang K, Huo R, Li Y, Zhou Z, Chen K, Zheng M, Zhang S, Xu T..  (2023)  Design, Synthesis, and Bioevaluation of Pyrido[2,3-d]pyrimidin-7-ones as Potent SOS1 Inhibitors.,  14  (2.0): [PMID:36793426] [10.1021/acsmedchemlett.2c00490]

4. Zhang S, Zhang Y, Chen X, Xu J, Fang H, Li Y, Liu Y, He H..  (2022)  Design and Structural Optimization of Orally Bioavailable SOS1 Inhibitors for the Treatment of KRAS-Driven Carcinoma.,  65  (23.0): [PMID:36384290] [10.1021/acs.jmedchem.2c01517]

5. 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]

6. Fan G, Lou L, Song Z, Zhang X, Xiong XF..  (2021)  Targeting mutated GTPase KRAS in tumor therapies.,  226  [PMID:34520956] [10.1016/j.ejmech.2021.113816]

7. Zhou Z, Zhou G, Zhou C, Fan Z, Cui R, Li Y, Li R, Gu Y, Li H, Ge Z, Cai X, Jiang B, Wang D, Zheng M, Xu T, Zhang S..  (2023)  Discovery of a Potent, Cooperative, and Selective SOS1 PROTAC ZZ151 with In Vivo Antitumor Efficacy in KRAS-Mutant Cancers.,  66  (6): [PMID:36897932] [10.1021/acs.jmedchem.3c00075]

8. Jiang H, Fan Y, Wang X, Wang J, Yang H, Fan W, Tang C..  (2023)  Design, synthesis and biological evaluation of quinazoline SOS1 inhibitors.,  88  [PMID:37011767] [10.1016/j.bmcl.2023.129265]

9. EUbOPEN.  (2023)  EUbOPEN Chemogenomics Library - IncuCyte,  [10.6019/CHEMBL5303304]

10. EUbOPEN.  (2023)  Tm Shift (DSF) assay results for EUbOPEN Chemogenomics Library,  [10.6019/CHEMBL5308504]

Source

Source(3):

• Scientific Literature
• Patent Bioactivity Data
• EUbOPEN Chemogenomic Library