6-[4-(5,7-dihydroxy-4-oxo-2-phenyl-chromen-8-yl)oxytriazol-1-yl]-N-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]hexanamide

ID: ALA5273209

Max Phase: Preclinical

Molecular Formula: C36H30N6O10

Molecular Weight: 706.67

Names and Identifiers

Canonical SMILES:  O=C1CCC(N2C(=O)c3cccc(NC(=O)CCCCCn4cc(Oc5c(O)cc(O)c6c(=O)cc(-c7ccccc7)oc56)nn4)c3C2=O)C(=O)N1

Standard InChI:  InChI=1S/C36H30N6O10/c43-23-16-25(45)32(33-31(23)24(44)17-26(51-33)19-8-3-1-4-9-19)52-29-18-41(40-39-29)15-6-2-5-12-27(46)37-21-11-7-10-20-30(21)36(50)42(35(20)49)22-13-14-28(47)38-34(22)48/h1,3-4,7-11,16-18,22,43,45H,2,5-6,12-15H2,(H,37,46)(H,38,47,48)

Standard InChI Key:  SWEBREOPLSSRRO-UHFFFAOYSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA5273209

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 706.67

Molecular Weight (Monoisotopic): 706.2023

AlogP: 3.86

#Rotatable Bonds: 11

Polar Surface Area: 223.26

Molecular Species: ACID

HBA: 13

HBD: 4

#RO5 Violations: 2

HBA (Lipinski): 16

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 5.53

CX Basic pKa: ┄

CX LogP: 4.17

CX LogD: 2.46

Aromatic Rings: 5

Heavy Atoms: 52

QED Weighted: 0.11

Np Likeness Score: -0.14

References

1. Huang Z, Wang T, Wang C, Fan Y..  (2022)  CDK9 inhibitors in cancer research.,  13  (6.0): [PMID:35814933] [10.1039/d2md00040g]

2. Joshi, Kalpana S KS and 7 more authors.  2007-03  In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00.  [PMID:17363486]

3. Squires, Matthew S MS and 7 more authors.  2009-02  Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.  [PMID:19174555]

4. Goh, K C KC and 15 more authors.  2012-02  TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties.  [PMID:21860433]

5. Hole, Alison J and 9 more authors.  2013-02-14  Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity.  [PMID:23252711]

6. Cirstea, D D and 15 more authors.  2013-12  Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs.  [PMID:23807770]

7. Martin, Mathew P MP, Olesen, Sanne H SH, Georg, Gunda I GI and Schönbrunn, Ernst E.  2013-11-15  Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains.  [PMID:24007471]

8. 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]

9. Bisi, John E JE, Sorrentino, Jessica A JA, Roberts, Patrick J PJ, Tavares, Francis X FX and Strum, Jay C JC.  2016-05  Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression.  [PMID:26826116]

10. Sonawane, Yogesh A and 5 more authors.  2016-10-13  Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy.  [PMID:27171036]

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

12. Patel, Hetal H and 15 more authors.  2018-06  ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment.  [PMID:29545334]

13. Wang, Yiting Y and 6 more authors.  2018-07-23  Design, synthesis and biological evaluation of pyrimidine derivatives as novel CDK2 inhibitors that induce apoptosis and cell cycle arrest in breast cancer cells.  [PMID:29853338]

14. 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]

15. Ito, Masahiro M and 18 more authors.  2018-09-13  Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors.  [PMID:30067358]

16. Teng, Yuou and 10 more authors.  2019-12-01  Recent advances in the development of cyclin-dependent kinase 7 inhibitors.  [PMID:31514062]

17. Wu, Tizhi and 6 more authors.  2020-11-25  Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update.  [PMID:32866383]

18. Barlaam, Bernard and 40 more authors.  2020-12-24  Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies.  [PMID:33306391]

Source

Source(1):

• Scientific Literature