6-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(3-chloro-2-(cyclopropylamino)pyridin-4-yl)-5-methyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one

ID: ALA4439006

Cas Number: 2235394-90-6

PubChem CID: 124147932

Product Number: S650586, Order Now?

Max Phase: Preclinical

Molecular Formula: C23H29ClN8O2

Molecular Weight: 484.99

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  C[C@@H]1OCC2(CCN(c3nc4[nH]nc(-c5ccnc(NC6CC6)c5Cl)c4c(=O)n3C)CC2)[C@@H]1N

Standard InChI:  InChI=1S/C23H29ClN8O2/c1-12-18(25)23(11-34-12)6-9-32(10-7-23)22-28-19-15(21(33)31(22)2)17(29-30-19)14-5-8-26-20(16(14)24)27-13-3-4-13/h5,8,12-13,18H,3-4,6-7,9-11,25H2,1-2H3,(H,26,27)(H,29,30)/t12-,18+/m0/s1

Standard InChI Key:  URUPFUYPXLMTMT-KPZWWZAWSA-N

Molfile:  

 
     RDKit          2D

 34 39  0  0  0  0  0  0  0  0999 V2000
   29.7408  -27.6858    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.7366  -28.5030    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.5126  -28.7595    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   30.9963  -28.1008    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.5192  -27.4373    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.1690  -24.9835    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.9885  -24.9847    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.3996  -24.2761    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.9881  -23.5658    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.1654  -23.5687    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7622  -24.2778    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.2240  -24.2731    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.4858  -23.8647    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.7045  -23.6080    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   27.4856  -24.6861    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.7057  -24.9368    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.5358  -25.7337    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.1429  -26.2856    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   27.9229  -26.0309    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0957  -25.2283    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.5324  -26.5788    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   28.3541  -27.3823    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.9601  -27.9339    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9179  -26.8797    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.3084  -26.3269    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.7537  -25.9838    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   26.9706  -27.0886    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.3997  -22.8575    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   23.7533  -22.8630    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   22.9361  -22.8671    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.2261  -22.4648    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.2302  -23.2820    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.7757  -26.6614    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.8135  -28.1049    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  1  0
  4  5  1  0
  5  1  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
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 15 13  1  0
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  8 12  1  0
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 15 20  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  2  0
 21 22  1  0
 21 25  1  0
 22 23  1  0
 23  1  1  0
  1 24  1  0
 24 25  1  0
 19 21  1  0
 17 26  2  0
 18 27  1  0
  9 28  1  0
 10 29  1  0
 29 30  1  0
 31 30  1  0
 32 31  1  0
 30 32  1  0
  5 33  1  6
  4 34  1  6
M  END

Alternative Forms

1. Parent:

   

   ALA4439006

   SHP389

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: 484.99

Molecular Weight (Monoisotopic): 484.2102

AlogP: 2.28

#Rotatable Bonds: 4

Polar Surface Area: 126.98

Molecular Species: BASE

HBA: 9

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.13

CX Basic pKa: 9.13

CX LogP: 1.01

CX LogD: -0.44

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.51

Np Likeness Score: -0.62

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. Bagdanoff JT, Chen Z, Acker M, Chen YN, Chan H, Dore M, Firestone B, Fodor M, Fortanet J, Hentemann M, Kato M, Koenig R, LaBonte LR, Liu S, Mohseni M, Ntaganda R, Sarver P, Smith T, Sendzik M, Stams T, Spence S, Towler C, Wang H, Wang P, Williams SL, LaMarche MJ..  (2019)  Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors.,  62  (4): [PMID:30688462] [10.1021/acs.jmedchem.8b01725]

3. 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