(3R,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine

ID: ALA4743002

PubChem CID: 118247772

Max Phase: Preclinical

Molecular Formula: C18H24ClN7OS

Molecular Weight: 421.96

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  C[C@H]1OCC2(CCN(c3cnc(Sc4ccnc(N)c4Cl)c(N)n3)CC2)[C@@H]1N

Standard InChI:  InChI=1S/C18H24ClN7OS/c1-10-14(20)18(9-27-10)3-6-26(7-4-18)12-8-24-17(16(22)25-12)28-11-2-5-23-15(21)13(11)19/h2,5,8,10,14H,3-4,6-7,9,20H2,1H3,(H2,21,23)(H2,22,25)/t10-,14-/m1/s1

Standard InChI Key:  UCJZOKGUEJUNIO-QMTHXVAHSA-N

Molfile:  

 
     RDKit          2D

 28 31  0  0  0  0  0  0  0  0999 V2000
   16.9340  -15.9397    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9298  -16.7569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7058  -17.0134    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.1895  -16.3547    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7124  -15.6912    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1030  -13.4860    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3979  -13.8943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8120  -13.8948    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.3977  -14.7115    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.1067  -15.1203    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8118  -14.7120    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5207  -15.1208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.5205  -15.9380    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2294  -16.3468    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9348  -15.1212    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2299  -14.7124    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6900  -13.4861    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   11.9825  -13.8951    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2781  -13.4844    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5711  -13.8927    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5711  -14.7107    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.2840  -15.1188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9881  -14.7081    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8634  -13.4841    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.2798  -12.6672    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   17.9689  -14.9153    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.1022  -12.6688    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.0067  -16.3588    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  1  0
  6  8  2  0
  7  9  2  0
  9 10  1  0
 10 11  2  0
  8 11  1  0
 12 13  1  0
 13 14  1  0
 14  1  1  0
  1 15  1  0
 15 16  1  0
 12 16  1  0
 11 12  1  0
  7 17  1  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 18  1  0
 20 24  1  0
 19 25  1  0
  5 26  1  6
  6 27  1  0
  4 28  1  1
M  END

Alternative Forms

1. Parent:

   

   ALA4743002

   (3R,4S)-8-[6-amino-5-(2-amino-3-chloropyridin-4-yl)sulfanylpyrazin-2-yl]-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine

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: 421.96

Molecular Weight (Monoisotopic): 421.1452

AlogP: 2.17

#Rotatable Bonds: 3

Polar Surface Area: 129.20

Molecular Species: BASE

HBA: 9

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 9.48

CX LogP: 1.66

CX LogD: -0.38

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.68

Np Likeness Score: -0.49

References

1. LaMarche MJ,Acker M,Argintaru A,Bauer D,Boisclair J,Chan H,Chen CH,Chen YN,Chen Z,Deng Z,Dore M,Dunstan D,Fan J,Fekkes P,Firestone B,Fodor M,Garcia-Fortanet J,Fortin PD,Fridrich C,Giraldes J,Glick M,Grunenfelder D,Hao HX,Hentemann M,Ho S,Jouk A,Kang ZB,Karki R,Kato M,Keen N,Koenig R,LaBonte LR,Larrow J,Liu G,Liu S,Majumdar D,Mathieu S,Meyer MJ,Mohseni M,Ntaganda R,Palermo M,Perez L,Pu M,Ramsey T,Reilly J,Sarver P,Sellers WR,Sendzik M,Shultz MD,Slisz J,Slocum K,Smith T,Spence S,Stams T,Straub C,Tamez V,Toure BB,Towler C,Wang P,Wang H,Williams SL,Yang F,Yu B,Zhang JH,Zhu S.  (2020)  Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer.,  63  (22): [PMID:32910655] [10.1021/acs.jmedchem.0c01170]

Source

Source(1):

• Scientific Literature