(Z)-3-(2-(2,3-dichlorophenyl)-2-oxoethylidene)-3,4-dihydroquinoxalin-2(1H)-one

ID: ALA4782076

PubChem CID: 162665009

Max Phase: Preclinical

Molecular Formula: C16H10Cl2N2O2

Molecular Weight: 333.17

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  O=C1Nc2ccccc2N/C1=C\C(=O)c1cccc(Cl)c1Cl

Standard InChI:  InChI=1S/C16H10Cl2N2O2/c17-10-5-3-4-9(15(10)18)14(21)8-13-16(22)20-12-7-2-1-6-11(12)19-13/h1-8,19H,(H,20,22)/b13-8-

Standard InChI Key:  SVNHGWNBISNBMG-JYRVWZFOSA-N

Molfile:  

 
     RDKit          2D

 22 24  0  0  0  0  0  0  0  0999 V2000
   23.4082  -22.7162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.4082  -23.5358    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.1151  -23.9447    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.8220  -23.5378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.8220  -22.7126    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.1133  -22.3074    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.5332  -22.2988    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.2467  -22.7147    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.2467  -23.5399    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.5309  -23.9492    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.9509  -23.9505    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.9509  -24.7676    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6575  -25.1782    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6575  -25.9943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3572  -26.4048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.0640  -25.9956    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.0640  -25.1766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3604  -24.7700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3572  -27.2220    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   26.9416  -26.3992    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   26.2421  -25.1742    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   26.9566  -22.3078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  5  4  1  0
  5  6  2  0
  6  1  1  0
  5  7  1  0
  8  7  1  0
  9  8  1  0
 10  9  1  0
  4 10  1  0
  9 11  2  0
 11 12  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 17 16  1  0
 18 17  2  0
 18 13  1  0
 15 19  1  0
 14 20  1  0
 12 21  2  0
  8 22  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4782076

   ---

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: 333.17

Molecular Weight (Monoisotopic): 332.0119

AlogP: 4.12

#Rotatable Bonds: 2

Polar Surface Area: 58.20

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.90

CX Basic pKa: ┄

CX LogP: 3.30

CX LogD: 3.30

Aromatic Rings: 2

Heavy Atoms: 22

QED Weighted: 0.64

Np Likeness Score: -0.73

References

1. Dou X,Huang H,Jiang L,Zhu G,Jin H,Jiao N,Zhang L,Liu Z,Zhang L.  (2020)  Rational modification, synthesis and biological evaluation of 3,4-dihydroquinoxalin-2(1H)-one derivatives as potent and selective c-Jun N-terminal kinase 3 (JNK3) inhibitors.,  201  [PMID:32603981] [10.1016/j.ejmech.2020.112445]

2. Bennett, B L BL and 12 more authors.  2001-11-20  SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.  [PMID:11717429]

3. Szczepankiewicz, Bruce G BG and 25 more authors.  2006-06-15  Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.  [PMID:16759099]

4. Zhao, Hongyu H and 19 more authors.  2006-07-27  Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.  [PMID:16854050]

5. Zarrinkar, Patrick P PP and 15 more authors.  2009-10-01  AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).  [PMID:19654408]

6. Kamenecka, Ted and 13 more authors.  2010-01-14  Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.  [PMID:19947601]

7. Goldstein, David M and 37 more authors.  2011-04-14  Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase.  [PMID:21375264]

8. Stebbins, John L and 9 more authors.  2011-09-22  Design and characterization of a potent and selective dual ATP- and substrate-competitive subnanomolar bidentate c-Jun N-terminal kinase (JNK) inhibitor.  [PMID:21815634]

9. Zhang, Tinghu and 17 more authors.  2012-01-27  Discovery of potent and selective covalent inhibitors of JNK.  [PMID:22284361]

10. Gong, Leyi L and 19 more authors.  2012-12-15  Discovery of a novel series of 4-quinolone JNK inhibitors.  [PMID:23142618]

11. Kusakabe, Ken-ichi K and 26 more authors.  2013-06-13  Indazole-based potent and cell-active Mps1 kinase inhibitors: rational design from pan-kinase inhibitor anthrapyrazolone (SP600125).  [PMID:23634759]

12. Li, Bei B and 14 more authors.  2013-09-15  Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors.  [PMID:23916259]

13. He, Yuanjun and 9 more authors.  2014-01-01  Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.  [PMID:24332487]

14. Patel, Snahel S and 26 more authors.  2015-01-08  Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models.  [PMID:25341110]

15. Koch, Pierre P, Gehringer, Matthias M and Laufer, Stefan A SA.  2015-01-08  Inhibitors of c-Jun N-terminal kinases: an update.  [PMID:25415535]

16. Patel, Snahel S and 19 more authors.  2015-10-22  Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).  [PMID:26431428]

17. Simon-Szabó, Laura L and 14 more authors.  2016-01-15  Novel compounds reducing IRS-1 serine phosphorylation for treatment of diabetes.  [PMID:26704265]

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

19. Schepetkin, Igor A and 11 more authors.  2019-01-01  Synthesis, biological evaluation, and molecular modeling of 11H-indeno[1,2-b]quinoxalin-11-one derivatives and tryptanthrin-6-oxime as c-Jun N-terminal kinase inhibitors.  [PMID:30347329]

20. Riggs, Jennifer R JR and 18 more authors.  2019-05-09  Design and Optimization Leading to an Orally Active TTK Protein Kinase Inhibitor with Robust Single Agent Efficacy.  [PMID:30998356]

21. Hatcher, John M and 8 more authors.  2020-11-12  Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma.  [PMID:33214835]

Source

Source(1):

• Scientific Literature