3-(4-Amino-4-methylpiperidin-1-yl)-6-(2,3-dichlorophenyl)-1,2,4-triazin-5-amine

ID: ALA4540461

PubChem CID: 118239663

Max Phase: Preclinical

Molecular Formula: C15H18Cl2N6

Molecular Weight: 353.26

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC1(N)CCN(c2nnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1

Standard InChI:  InChI=1S/C15H18Cl2N6/c1-15(19)5-7-23(8-6-15)14-20-13(18)12(21-22-14)9-3-2-4-10(16)11(9)17/h2-4H,5-8,19H2,1H3,(H2,18,20,22)

Standard InChI Key:  VTTSGEFPLPXNHH-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 23 25  0  0  0  0  0  0  0  0999 V2000
    9.5884   -8.0545    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.2860   -8.4743    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.0021   -8.0813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0165   -7.2643    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3189   -6.8404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6028   -7.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3333   -6.0234    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.9011   -6.8177    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9155   -6.0007    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2179   -5.5767    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5018   -5.9738    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4874   -6.7908    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1850   -7.2107    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2323   -4.7597    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    9.6316   -5.6035    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   11.7038   -8.5012    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.6894   -9.3182    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3870   -9.7421    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.1031   -9.3450    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.1175   -8.5280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4158   -8.1082    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3691  -10.1198    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9094   -9.2184    0.0000 N   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
  1  6  1  0
  5  7  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
  8 13  2  0
 10 14  1  0
  9 15  1  0
  6  8  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 16 21  1  0
 19 22  1  0
 19 23  1  0
  3 16  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4540461

   3-(4-Amino-4-methylpiperidin-1-yl)-6-(2,3-dichlorophenyl)-1,2,4-triazin-5-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: 353.26

Molecular Weight (Monoisotopic): 352.0970

AlogP: 2.75

#Rotatable Bonds: 2

Polar Surface Area: 93.95

Molecular Species: BASE

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 10.27

CX LogP: 2.36

CX LogD: -0.33

Aromatic Rings: 2

Heavy Atoms: 23

QED Weighted: 0.86

Np Likeness Score: -0.92

References

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2. 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]

3. Lawrence, Harshani R and 10 more authors.  2008-08-28  Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds.  [PMID:18680359]

4. Geronikaki, A A and 5 more authors.  2008-09-11  2-Thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones as new agents with SHP-2 inhibitory action.  [PMID:18702480]

5. Dawson, Marcia I MI and 21 more authors.  2008-09-25  Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of SRC homology 2 domain-containing protein tyrosine phosphatase-2 activity.  [PMID:18759424]

6. He, Yantao and 6 more authors.  2013-02-14  Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic acid scaffold.  [PMID:23305444]

7. He, Yantao Y and 11 more authors.  2013-06-27  A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases.  [PMID:23713581]

8. Zeng, Li-Fan LF and 12 more authors.  2014-08-14  Therapeutic potential of targeting the oncogenic SHP2 phosphatase.  [PMID:25003231]

9. Tautz, Lutz L, Senis, Yotis A YA, Oury, Cécile C and Rahmouni, Souad S.  2015-06-15  Perspective: Tyrosine phosphatases as novel targets for antiplatelet therapy.  [PMID:25921264]

10. Sun, Wenlong W and 6 more authors.  2017-08-01  Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.  [PMID:28642102]

11. Xie, Jingjing J and 10 more authors.  2017-12-28  Allosteric Inhibitors of SHP2 with Therapeutic Potential for Cancer Treatment.  [PMID:29155585]

12. Du, Yongli Y, Zhang, Yanhui Y, Ling, Hao H, Li, Qunyi Q and Shen, Jingkang J.  2018-01-20  Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site.  [PMID:29289892]

13. Kim, Bohee and 6 more authors.  2020-01-01  Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene.  [PMID:31784318]

14. Wang, Mingliang; Lu, Jianfeng; Wang, Mi; Yang, Chao-Yie and Wang, Shaomeng.  2020-07-23  Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein.  [PMID:32437146]

15. Yuan, Xinrui; Bu, Hong; Zhou, Jinpei; Yang, Chao-Yie and Zhang, Huibin.  2020-10-22  Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application.  [PMID:32460492]

Source

Source(1):

• Scientific Literature