N-(5-cyclobutyl-1H-pyrazol-3-yl)-2-(4-(5-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yloxy)pentyloxy)phenyl)acetamide

ID: ALA4519788

Cas Number: 2118356-96-8

PubChem CID: 132472236

Product Number: P650019, Order Now?

Max Phase: Preclinical

Molecular Formula: C33H35N5O7

Molecular Weight: 613.67

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  O=C1CCC(N2C(=O)c3cccc(OCCCCCOc4ccc(CC(=O)Nc5cc(C6CCC6)[nH]n5)cc4)c3C2=O)C(=O)N1

Standard InChI:  InChI=1S/C33H35N5O7/c39-28-15-14-25(31(41)35-28)38-32(42)23-8-5-9-26(30(23)33(38)43)45-17-3-1-2-16-44-22-12-10-20(11-13-22)18-29(40)34-27-19-24(36-37-27)21-6-4-7-21/h5,8-13,19,21,25H,1-4,6-7,14-18H2,(H,35,39,41)(H2,34,36,37,40)

Standard InChI Key:  WCEHIDWONYOKOJ-UHFFFAOYSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4519788

   PROTAC CDK9 Degrader-1

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: 613.67

Molecular Weight (Monoisotopic): 613.2536

AlogP: 3.89

#Rotatable Bonds: 13

Polar Surface Area: 159.79

Molecular Species: NEUTRAL

HBA: 8

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.13

CX Basic pKa: 2.00

CX LogP: 3.56

CX LogD: 3.56

Aromatic Rings: 3

Heavy Atoms: 45

QED Weighted: 0.19

Np Likeness Score: -0.75

References

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2. Wu T,Qin Z,Tian Y,Wang J,Xu C,Li Z,Bian J.  (2020)  Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update.,  63  (22): [PMID:32866383] [10.1021/acs.jmedchem.0c00744]

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

4. Marak BN, Dowarah J, Khiangte L, Singh VP..  (2020)  A comprehensive insight on the recent development of Cyclic Dependent Kinase inhibitors as anticancer agents.,  203  [PMID:32707525] [10.1016/j.ejmech.2020.112571]

5. Wang C, Zhang Y, Wu Y, Xing D..  (2021)  Developments of CRBN-based PROTACs as potential therapeutic agents.,  225  [PMID:34411892] [10.1016/j.ejmech.2021.113749]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

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

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

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

17. 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]

18. 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]

19. 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]

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

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

22. 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