Cyclopropanecarboxylic acid [6-(3-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-amide

ID: ALA408019

PubChem CID: 6539569

Max Phase: Preclinical

Molecular Formula: C16H14N4O2

Molecular Weight: 294.31

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Nc1n[nH]c2nc(-c3cccc(O)c3)ccc12)C1CC1

Standard InChI:  InChI=1S/C16H14N4O2/c21-11-3-1-2-10(8-11)13-7-6-12-14(17-13)19-20-15(12)18-16(22)9-4-5-9/h1-3,6-9,21H,4-5H2,(H2,17,18,19,20,22)

Standard InChI Key:  AXWDQRXGOKDXJT-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 22 25  0  0  0  0  0  0  0  0999 V2000
   13.3939  -23.7343    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3927  -24.5618    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1055  -24.9747    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.1036  -23.3216    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8217  -23.7303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8222  -24.5618    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6132  -24.8183    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.1016  -24.1452    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6124  -23.4729    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8667  -22.6882    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.6735  -22.5162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9278  -21.7315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2259  -23.1288    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.6804  -24.9714    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9664  -24.5562    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2518  -24.9669    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2502  -25.7927    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9690  -26.2060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6805  -25.7929    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5349  -21.1782    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7502  -20.9239    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9708  -27.0309    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  5  6  1  0
 10 11  1  0
 11 12  1  0
  2  3  1  0
 11 13  2  0
  3  6  2  0
  1  2  2  0
 14 15  2  0
  5  4  2  0
 15 16  1  0
  6  7  1  0
 16 17  2  0
  7  8  1  0
 17 18  1  0
  8  9  2  0
 18 19  2  0
 19 14  1  0
  2 14  1  0
 20 12  1  0
 21 20  1  0
 12 21  1  0
  9  5  1  0
  4  1  1  0
  9 10  1  0
 18 22  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA408019

   N-[6-(3-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]cyclopropanecarboxamide

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: 294.31

Molecular Weight (Monoisotopic): 294.1117

AlogP: 2.68

#Rotatable Bonds: 3

Polar Surface Area: 90.90

Molecular Species: NEUTRAL

HBA: 4

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 9.56

CX Basic pKa: 0.92

CX LogP: 2.79

CX LogD: 2.78

Aromatic Rings: 3

Heavy Atoms: 22

QED Weighted: 0.69

Np Likeness Score: -1.20

References

1. Witherington J, Bordas V, Gaiba A, Garton NS, Naylor A, Rawlings AD, Slingsby BP, Smith DG, Takle AK, Ward RW..  (2003)  6-aryl-pyrazolo[3,4-b]pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3).,  13  (18): [PMID:12941332] [10.1016/s0960-894x(03)00645-0]

2. Witherington J, Bordas V, Gaiba A, Naylor A, Rawlings AD, Slingsby BP, Smith DG, Takle AK, Ward RW..  (2003)  6-heteroaryl-pyrazolo[3,4-b]pyridines: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3).,  13  (18): [PMID:12941333] [10.1016/s0960-894x(03)00646-2]

3. Taha MO, Bustanji Y, Al-Ghussein MA, Mohammad M, Zalloum H, Al-Masri IM, Atallah N..  (2008)  Pharmacophore modeling, quantitative structure-activity relationship analysis, and in silico screening reveal potent glycogen synthase kinase-3beta inhibitory activities for cimetidine, hydroxychloroquine, and gemifloxacin.,  51  (7): [PMID:18324764] [10.1021/jm7009765]

4. Patel DS, Bharatam PV..  (2008)  Selectivity criterion for pyrazolo[3,4-b]pyrid[az]ine derivatives as GSK-3 inhibitors: CoMFA and molecular docking studies.,  43  (5): [PMID:17707953] [10.1016/j.ejmech.2007.06.016]

5. Bamborough P, Drewry D, Harper G, Smith GK, Schneider K..  (2008)  Assessment of chemical coverage of kinome space and its implications for kinase drug discovery.,  51  (24): [PMID:19035792] [10.1021/jm8011036]

6. Simon Townson and Suzanne Gokool. GlaxoSmithKline Published Kinase Inhibitor Set 2 Onchocerca lienalis Screening Data,  [10.6019/CHEMBL3988181]

7. Coghlan, M P MP and 17 more authors.  2000-10  Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription.  [PMID:11033082]

8. Mettey, Yvette Y and 9 more authors.  2003-01-16  Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects.  [PMID:12519061]

9. Ring, David B DB and 12 more authors.  2003-03  Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo.  [PMID:12606497]

10. Meijer, Laurent L, Flajolet, Marc M and Greengard, Paul P.  2004-09  Pharmacological inhibitors of glycogen synthase kinase 3.  [PMID:15559249]

11. Lo Monte, Fabio and 14 more authors.  2012-05-10  Identification of glycogen synthase kinase-3 inhibitors with a selective sting for glycogen synthase kinase-3α.  [PMID:22533818]

12. Göring, Stefan S, Taymans, Jean-Marc JM, Baekelandt, Veerle V and Schmidt, Boris B.  2014-10-01  Indolinone based LRRK2 kinase inhibitors with a key hydrogen bond.  [PMID:25219901]

13. Paiva, Cody C and 8 more authors.  2015  Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.  [PMID:26606677]

14. Wagman, Allan S AS and 21 more authors.  2017-10-26  Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3.  [PMID:29016121]

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

16. 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]

17. Wang, Yanxing Y and 6 more authors.  2019-06-01  Discovery of novel glycogen synthase kinase-3α inhibitors: Structure-based virtual screening, preliminary SAR and biological evaluation for treatment of acute myeloid leukemia.  [PMID:30925338]

18. Yu, Mingfeng and 15 more authors.  2021-02-03  Potent and orally bioavailable CDK8 inhibitors: Design, synthesis, structure-activity relationship analysis and biological evaluation.  [PMID:33571827]

Source

Source(2):

• Scientific Literature
• Published Kinase Inhibitor Set 2