(S)-2-(1-Hydroxy-but-2-ylamino)-6-[3-(5-pyrimidinyl)phenylamino]-9-iso-propylpurine

ID: ALA2295944

PubChem CID: 76313101

Max Phase: Preclinical

Molecular Formula: C22H26N8O

Molecular Weight: 418.51

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CCC[C@H](O)Nc1nc(Nc2cccc(-c3cncnc3)c2)c2ncn(C(C)C)c2n1

Standard InChI:  InChI=1S/C22H26N8O/c1-4-6-18(31)27-22-28-20(19-21(29-22)30(13-25-19)14(2)3)26-17-8-5-7-15(9-17)16-10-23-12-24-11-16/h5,7-14,18,31H,4,6H2,1-3H3,(H2,26,27,28,29)/t18-/m0/s1

Standard InChI Key:  CFVOEIRDSYTLGT-SFHVURJKSA-N

Molfile:  

     RDKit          2D

 31 34  0  0  0  0  0  0  0  0999 V2000
   31.8690   -2.9881    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.8679   -3.8076    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.5759   -4.2166    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   32.5742   -2.5792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.1599   -4.2156    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   33.2828   -2.9845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.2830   -3.8031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.0617   -4.0559    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   34.5427   -3.3934    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.0613   -2.7313    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   34.3144   -4.8330    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.7678   -5.4404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.1138   -5.0027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.5717   -1.7620    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   33.2782   -1.3513    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.9850   -1.7602    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.6910   -1.3502    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.6890   -0.5321    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.9751   -0.1258    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.2720   -0.5381    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.3978   -1.7540    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.3985   -2.5723    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.1064   -2.9791    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.8141   -2.5687    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.8094   -1.7473    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.1009   -1.3442    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.4525   -3.8065    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.7444   -4.2145    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.0371   -3.8054    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.3290   -4.2134    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.4531   -2.9893    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  7  2  0
  6  4  2  0
  4  1  1  0
  2  5  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  2  0
 10  6  1  0
  8 11  1  0
 11 12  1  0
 11 13  1  0
  4 14  1  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 15  1  0
 21 22  2  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  2  0
 26 21  1  0
 17 21  1  0
  5 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 27 31  1  6
M  END

Alternative Forms

1. Parent:

   

   ALA2295944

   (1S)-1-[[9-propan-2-yl-6-(3-pyrimidin-5-ylanilino)purin-2-yl]amino]butan-1-ol

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: 418.51

Molecular Weight (Monoisotopic): 418.2230

AlogP: 4.14

#Rotatable Bonds: 8

Polar Surface Area: 113.67

Molecular Species: NEUTRAL

HBA: 9

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.51

CX Basic pKa: 3.67

CX LogP: 3.34

CX LogD: 3.34

Aromatic Rings: 4

Heavy Atoms: 31

QED Weighted: 0.37

Np Likeness Score: -0.95

References

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2. 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]

3. Göckler, Nora N and 5 more authors.  2009-11  Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation.  [PMID:19796173]

4. Mott, Bryan T and 11 more authors.  2009-12-01  Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk).  [PMID:19837585]

5. Rosenthal, Andrew S and 9 more authors.  2011-05-15  Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk).  [PMID:21450467]

6. Debdab, Mansour M and 16 more authors.  2011-06-23  Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing.  [PMID:21615147]

7. Tahtouh, Tania T and 15 more authors.  2012-11-08  Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.  [PMID:22998443]

8. Burgy, Guillaume G and 7 more authors.  2013-04  Chemical synthesis and biological validation of immobilized protein kinase inhibitory Leucettines.  [PMID:23454515]

9. Coombs, Thomas C and 8 more authors.  2013-06-15  Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315.  [PMID:23642479]

10. and Rosse, Gerard G.  2013-06-13  Tricyclic Pyrimidines As Inhibitors of DYRK1A/DYRK1B As Potential Treatment for Down's Syndrome or Alzheimer's Disease.  [PMID:24900699]

11. Falke, Hannes H and 12 more authors.  2015-04-09  10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A.  [PMID:25730262]

12. Mariano, Marica M, Hartmann, Rolf W RW and Engel, Matthias M.  2016-04-13  Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2.  [PMID:26896709]

13. Labrière, Christophe C, Lozach, Olivier O, Blairvacq, Mélina M, Meijer, Laurent L and Guillou, Catherine C.  2016-11-29  Further investigation of Paprotrain: Towards the conception of selective and multi-targeted CNS kinase inhibitors.  [PMID:27676471]

14. Murár, Miroslav M and 5 more authors.  2017-01-27  Novel CLK1 inhibitors based on N-aryloxazol-2-amine skeleton - A possible way to dual VEGFR2 TK/CLK ligands.  [PMID:27940419]

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

16. Jarhad, Dnyandev B DB, Mashelkar, Karishma K KK, Kim, Hong-Rae HR, Noh, Minsoo M and Jeong, Lak Shin LS.  2018-11-21  Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Inhibitors as Potential Therapeutics.  [PMID:29985601]

17. Kumar, Kunal K and 5 more authors.  2018-09-13  Development of Kinase-Selective, Harmine-Based DYRK1A Inhibitors that Induce Pancreatic Human β-Cell Proliferation.  [PMID:30059217]

18. Darwish, Sarah S SS and 5 more authors.  2018-09-05  Development of novel 2,4-bispyridyl thiophene-based compounds as highly potent and selective Dyrk1A inhibitors. Part I: Benzamide and benzylamide derivatives.  [PMID:30193214]

19. Darwish, Sarah S SS and 6 more authors.  2018-10-05  Development of novel amide-derivatized 2,4-bispyridyl thiophenes as highly potent and selective Dyrk1A inhibitors. Part II: Identification of the cyclopropylamide moiety as a key modification.  [PMID:30223116]

20. 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]

21. Vanda, David D, Zajdel, Paweł P and Soural, Miroslav M.  2019-07-31  Imidazopyridine-based selective and multifunctional ligands of biological targets associated with psychiatric and neurodegenerative diseases.  [PMID:31404862]

22. Allegretti, Paul A and 8 more authors.  2020-01-01  Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization.  [PMID:31757680]

23. Kumar, Kunal and 12 more authors.  2020-03-26  Synthesis and Biological Validation of a Harmine-Based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor.  [PMID:32003560]

24. Liu, Yahu A and 40 more authors.  2020-03-26  Selective DYRK1A Inhibitor for the Treatment of Type 1 Diabetes: Discovery of 6-Azaindole Derivative GNF2133.  [PMID:32077280]

25. Jiang, Xueyang and 11 more authors.  2020-12-01  Rational design and biological evaluation of a new class of thiazolopyridyl tetrahydroacridines as cholinesterase and GSK-3 dual inhibitors for Alzheimer's disease.  [PMID:32950908]

26. and Kargbo, Robert B.  2020-10-08  Selective DYRK1A Inhibitor for the Treatment of Neurodegenerative Diseases: Alzheimer, Parkinson, Huntington, and Down Syndrome.  [PMID:33062155]

Source

Source(1):

• Scientific Literature