2-((3,5-difluoro-4-hydroxyphenyl)amino)-8-isopentyl-5,7-dimethyl-7,8-dihydropteridin-6(5H)-one

ID: ALA573107

Cas Number: 501437-28-1

PubChem CID: 25023738

Product Number: B126041, Order Now?

Max Phase: Preclinical

Molecular Formula: C19H23F2N5O2

Molecular Weight: 391.42

Molecule Type: Small molecule

Names and Identifiers

Synonyms: BI-D1870 | BI-D1870|501437-28-1|2-((3,5-difluoro-4-hydroxyphenyl)amino)-8-isopentyl-5,7-dimethyl-7,8-dihydropteridin-6(5H)-one|BI-D 1870|2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-(3-methylbutyl)-7H-pteridin-6-one|2-[(3,5-DIFLUORO-4-HYDROXYPHENYL)AMINO]-7,8-DIHYDRO-5,7-DIMETHYL-8-(3-METHYLBUTYL)-6(5H)-PTERIDINONE|2-((3,5-difluoro-4-hydroxyphenyl)amino)-8-isopentyl-5,7-dimethyl-7,8-dihydropteridin-6(5H)-one.|WLN44M8WHJ|CHEMBL573107|GTPL8038|SCHEMBL13881333|BDBM25017|BID1870|DTXSID40648506|BShow More⌵

Canonical SMILES:  CC(C)CCN1c2nc(Nc3cc(F)c(O)c(F)c3)ncc2N(C)C(=O)C1C

Standard InChI:  InChI=1S/C19H23F2N5O2/c1-10(2)5-6-26-11(3)18(28)25(4)15-9-22-19(24-17(15)26)23-12-7-13(20)16(27)14(21)8-12/h7-11,27H,5-6H2,1-4H3,(H,22,23,24)

Standard InChI Key:  DTEKTGDVSARYDS-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 28 30  0  0  0  0  0  0  0  0999 V2000
    3.7111   -1.1291    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7099   -1.9565    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4247   -2.3694    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.4229   -0.7164    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1383   -1.1255    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1391   -1.9523    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8544   -2.3633    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.5694   -1.9485    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5646   -1.1186    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8487   -0.7113    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.2766   -0.7017    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.8444    0.1136    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2855   -2.3583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8561   -3.1883    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2667   -3.7708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2625   -4.5958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9750   -5.0083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5458   -5.0042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9951   -2.3684    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.2810   -1.9554    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2862   -1.1305    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5729   -0.7175    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8571   -1.1295    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8591   -1.9588    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5730   -2.3680    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5740    0.1075    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    0.1424   -0.7174    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.1458   -2.3732    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  3  6  1  0
  7 14  1  0
  6  7  1  0
 14 15  1  0
  1  2  1  0
 15 16  1  0
  7  8  1  0
 16 17  1  0
  5  4  1  0
 16 18  1  0
  8  9  1  0
  2 19  1  0
  4  1  2  0
 19 20  1  0
  9 10  1  0
 20 21  1  0
 10  5  1  0
 21 22  2  0
 22 23  1  0
  9 11  2  0
 23 24  2  0
  2  3  2  0
 24 25  1  0
 25 20  2  0
 10 12  1  0
 22 26  1  0
  5  6  2  0
 23 27  1  0
  8 13  1  0
 24 28  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA573107

   BI-D1870

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: 391.42

Molecular Weight (Monoisotopic): 391.1820

AlogP: 3.42

#Rotatable Bonds: 5

Polar Surface Area: 81.59

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 8.28

CX Basic pKa: 4.19

CX LogP: 3.84

CX LogD: 3.78

Aromatic Rings: 2

Heavy Atoms: 28

QED Weighted: 0.76

Np Likeness Score: -0.87

References

1. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P..  (2007)  The selectivity of protein kinase inhibitors: a further update.,  408  (3): [PMID:17850214] [10.1042/bj20070797]

2. Yang LL, Li GB, Yan HX, Sun QZ, Ma S, Ji P, Wang ZR, Feng S, Zou J, Yang SY..  (2012)  Discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization.,  56  [PMID:22944772] [10.1016/j.ejmech.2012.08.007]

3. Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute,  [10.6019/CHEMBL1201861]

4. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

5. Serafim RAM, de Souza Gama FH, Dutra LA, Dos Reis CV, Vasconcelos SNS, da Silva Santiago A, Takarada JE, Di Pillo F, Azevedo H, Mascarello A, Elkins JM, Massirer KB, Gileadi O, Guimarães CRW, Couñago RM..  (2019)  Development of Pyridine-based Inhibitors for the Human Vaccinia-related Kinases 1 and 2.,  10  (9): [PMID:31531195] [10.1021/acsmedchemlett.9b00082]

6. Liosi ME, Krimmer SG, Newton AS, Dawson TK, Puleo DE, Cutrona KJ, Suzuki Y, Schlessinger J, Jorgensen WL..  (2020)  Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core.,  63  (10): [PMID:32329617] [10.1021/acs.jmedchem.0c00192]

7. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

8. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

9. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

10. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

11. Casalvieri KA, Matheson CJ, Backos DS, Reigan P..  (2020)  Substituted pteridinones as p90 ribosomal S6 protein kinase (RSK) inhibitors: A structure-activity study.,  28  (5): [PMID:31982240] [10.1016/j.bmc.2019.115303]

12. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

13. Casalvieri KA, Matheson CJ, Warfield BM, Backos DS, Reigan P..  (2021)  N-Substituted pyrrolopyrimidines and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors.,  41  [PMID:34034149] [10.1016/j.bmc.2021.116220]

14. Yuan Y, Xu J, Jiang L, Yu K, Ge Y, Li M, He H, Niu Q, Shi X, Fan L, Chen Z, Zhao Z, Li S, Xu Y, Wang Z, Li H..  (2021)  Discovery, Optimization, and Structure-Activity Relationship Study of Novel and Potent RSK4 Inhibitors as Promising Agents for the Treatment of Esophageal Squamous Cell Carcinoma.,  64  (18.0): [PMID:34496560] [10.1021/acs.jmedchem.1c00969]

15. Carlino L, Rastelli G..  (2016)  Dual Kinase-Bromodomain Inhibitors in Anticancer Drug Discovery: A Structural and Pharmacological Perspective.,  59  (20): [PMID:27559828] [10.1021/acs.jmedchem.6b00438]

Source

Source(4):

• Scientific Literature
• Sanger Institute Genomics of Drug Sensitivity in Cancer
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6