6-Amino-2-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-methyl-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrimidin-4(3H)-one

ID: ALA4476848

Cas Number: 2055757-40-7

PubChem CID: 124150499

Product Number: S646238, Order Now?

Max Phase: Preclinical

Molecular Formula: C20H25F3N6O2S

Molecular Weight: 470.52

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  C[C@@H]1OCC2(CCN(c3nc(N)c(Sc4cccnc4C(F)(F)F)c(=O)n3C)CC2)[C@@H]1N

Standard InChI:  InChI=1S/C20H25F3N6O2S/c1-11-14(24)19(10-31-11)5-8-29(9-6-19)18-27-16(25)13(17(30)28(18)2)32-12-4-3-7-26-15(12)20(21,22)23/h3-4,7,11,14H,5-6,8-10,24-25H2,1-2H3/t11-,14+/m0/s1

Standard InChI Key:  QZHZIDHAIVAHMD-SMDDNHRTSA-N

Molfile:  

 
     RDKit          2D

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    1.9249   -4.9715    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6329   -5.3805    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3426   -4.9710    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    2.6311   -3.7431    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    4.7551   -4.1430    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7556   -4.9574    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4608   -5.3633    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.1694   -4.9555    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    7.5775   -6.5876    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2896   -5.3644    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5815   -4.9514    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3223   -5.1585    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3601   -6.6020    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4608   -6.1805    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4545   -2.9098    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6287   -2.9259    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3352   -2.5152    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.9197   -2.5194    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.6208   -2.1049    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    4.0483   -5.3667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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  1 22  1  0
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  5 24  1  6
  4 25  1  6
 15 26  1  0
 18 27  1  0
 11 28  1  0
 28 29  1  0
 28 30  1  0
 28 31  1  0
 14 32  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4476848

   SHP394

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 470.52

Molecular Weight (Monoisotopic): 470.1712

AlogP: 2.26

#Rotatable Bonds: 3

Polar Surface Area: 112.29

Molecular Species: BASE

HBA: 9

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 9.18

CX LogP: 1.27

CX LogD: -0.49

Aromatic Rings: 2

Heavy Atoms: 32

QED Weighted: 0.70

Np Likeness Score: -0.60

References

1. Sarver P, Acker M, Bagdanoff JT, Chen Z, Chen YN, Chan H, Firestone B, Fodor M, Fortanet J, Hao H, Hentemann M, Kato M, Koenig R, LaBonte LR, Liu G, Liu S, Liu C, McNeill E, Mohseni M, Sendzik M, Stams T, Spence S, Tamez V, Tichkule R, Towler C, Wang H, Wang P, Williams SL, Yu B, LaMarche MJ..  (2019)  6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors.,  62  (4): [PMID:30688459] [10.1021/acs.jmedchem.8b01726]

2. Tang K, Zhao M, Wu YH, Wu Q, Wang S, Dong Y, Yu B, Song Y, Liu HM..  (2022)  Structure-based design, synthesis and biological evaluation of aminopyrazines as highly potent, selective, and cellularly active allosteric SHP2 inhibitors.,  230  [PMID:35063735] [10.1016/j.ejmech.2022.114106]

Source

Source(1):

• Scientific Literature