6-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-4-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

ID: ALA2348862

Cas Number: 1228012-18-7

PubChem CID: 58298312

Max Phase: Preclinical

Molecular Formula: C20H25N5O3

Molecular Weight: 383.45

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)(O)c1ccc(-c2cnc3c(n2)N(CC2CCOCC2)CC(=O)N3)cn1

Standard InChI:  InChI=1S/C20H25N5O3/c1-20(2,27)16-4-3-14(9-21-16)15-10-22-18-19(23-15)25(12-17(26)24-18)11-13-5-7-28-8-6-13/h3-4,9-10,13,27H,5-8,11-12H2,1-2H3,(H,22,24,26)

Standard InChI Key:  UWUPKVZQISLSSA-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 28 31  0  0  0  0  0  0  0  0999 V2000
   14.0185  -18.9194    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0176  -19.7387    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.7257  -20.1477    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4353  -19.7382    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4325  -18.9156    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7239  -18.5103    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1402  -20.1450    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1401  -20.9633    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8476  -21.3707    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.8437  -19.7358    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.3391  -18.4654    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6062  -18.8268    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.7395  -17.7553    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9224  -17.7553    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5487  -20.1365    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5582  -20.9585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.2708  -21.3590    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.9785  -20.9420    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.9690  -20.1200    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.2518  -19.7150    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.6904  -21.3433    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.2412  -18.8979    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5282  -18.4986    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5239  -17.6808    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8150  -17.2814    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1102  -17.6957    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.1189  -18.5138    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8324  -18.9176    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
  7  8  2  0
  8  9  1  0
  9 16  2  0
 15 10  2  0
 10  7  1  0
  4  7  1  0
  1 11  1  0
 11 12  1  0
 11 13  1  0
 11 14  1  0
 15 16  1  0
 15 20  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 18 21  2  0
 20 22  1  0
 22 23  1  0
 23 24  1  0
 23 28  1  0
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA2348862

   6-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-4-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 383.45

Molecular Weight (Monoisotopic): 383.1957

AlogP: 1.95

#Rotatable Bonds: 4

Polar Surface Area: 100.47

Molecular Species: NEUTRAL

HBA: 7

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.04

CX Basic pKa: 3.58

CX LogP: 1.33

CX LogD: 1.33

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.83

Np Likeness Score: -0.72

References

1. Mortensen DS, Sapienza J, Lee BG, Perrin-Ninkovic SM, Harris R, Shevlin G, Parnes JS, Whitefield B, Hickman M, Khambatta G, Bisonette RR, Peng S, Gamez JC, Leisten J, Narla RK, Fultz KE, Sankar S..  (2013)  Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase.,  23  (6): [PMID:23414803] [10.1016/j.bmcl.2013.01.110]

2. Mortensen DS, Perrin-Ninkovic SM, Shevlin G, Zhao J, Packard G, Bahmanyar S, Correa M, Elsner J, Harris R, Lee BG, Papa P, Parnes JS, Riggs JR, Sapienza J, Tehrani L, Whitefield B, Apuy J, Bisonette RR, Gamez JC, Hickman M, Khambatta G, Leisten J, Peng SX, Richardson SJ, Cathers BE, Canan SS, Moghaddam MF, Raymon HK, Worland P, Narla RK, Fultz KE, Sankar S..  (2015)  Discovery of mammalian target of rapamycin (mTOR) kinase inhibitor CC-223.,  58  (13): [PMID:26083478] [10.1021/acs.jmedchem.5b00626]

3. Oleksak P, Nepovimova E, Chrienova Z, Musilek K, Patocka J, Kuca K..  (2022)  Contemporary mTOR inhibitor scaffolds to diseases breakdown: A patent review (2015-2021).,  238  [PMID:35688004] [10.1016/j.ejmech.2022.114498]

4. Goodman, Krista B KB and 26 more authors.  2007-01-11  Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.  [PMID:17201405]

5. Okuzumi, Tatsuya and 6 more authors.  2009-07  Inhibitor hijacking of Akt activation.  [PMID:19465931]

6. Tolcher, Anthony A and 16 more authors.  2014-03  A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours.  [PMID:24440085]

7. Yoon, Hojong H and 5 more authors.  2016-01-14  A Pyrazolo[3,4-d]pyrimidin-4-amine Derivative Containing an Isoxazole Moiety Is a Selective and Potent Inhibitor of RET Gatekeeper Mutants.  [PMID:26652860]

8. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

9. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]

10. Chen, Ying and 9 more authors.  2020-09-24  p62/SQSTM1, a Central but Unexploited Target: Advances in Its Physiological/Pathogenic Functions and Small Molecular Modulators.  [PMID:32324396]

Source

Source(1):

• Scientific Literature