2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(3-(2-(2-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)ethoxy)ethoxy)propyl)acetamide

ID: ALA4547473

PubChem CID: 155553699

Max Phase: Preclinical

Molecular Formula: C49H61N11O10

Molecular Weight: 964.09

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCCOCCOCCOCCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Standard InChI:  InChI=1S/C49H61N11O10/c1-31-36-29-53-49(56-44(36)59(33-8-3-4-9-33)47(66)42(31)32(2)61)54-39-14-12-34(28-52-39)58-20-18-57(19-21-58)30-41(63)51-17-7-23-69-25-27-70-26-24-68-22-6-16-50-37-11-5-10-35-43(37)48(67)60(46(35)65)38-13-15-40(62)55-45(38)64/h5,10-12,14,28-29,33,38,50H,3-4,6-9,13,15-27,30H2,1-2H3,(H,51,63)(H,55,62,64)(H,52,53,54,56)

Standard InChI Key:  NAENXYHPJLZWFB-UHFFFAOYSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4547473

   ---

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: 964.09

Molecular Weight (Monoisotopic): 963.4603

AlogP: 3.14

#Rotatable Bonds: 23

Polar Surface Area: 248.62

Molecular Species: NEUTRAL

HBA: 18

HBD: 4

#RO5 Violations: 2

HBA (Lipinski): 21

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.15

CX Basic pKa: 6.22

CX LogP: 1.99

CX LogD: 1.97

Aromatic Rings: 4

Heavy Atoms: 70

QED Weighted: 0.05

Np Likeness Score: -1.02

References

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2. Gray, N S NS and 12 more authors.  1998-07-24  Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.  [PMID:9677190]

3. Kubo, A A and 9 more authors.  1999-12  The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4.  [PMID:10632371]

4. Soni, R R and 7 more authors.  2000-09-07  Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product.  [PMID:10973815]

5. Lane, M E ME and 9 more authors.  2001-08-15  A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells.  [PMID:11507069]

6. Tavares, Francis X FX and 7 more authors.  2004-09-09  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy.  [PMID:15341487]

7. Fry, David W DW and 10 more authors.  2004-11  Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts.  [PMID:15542782]

8. Pennati, Marzia M and 12 more authors.  2005-09  Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation.  [PMID:16170024]

9. Sridhar, Jayalakshmi J, Akula, Nagaraju N and Pattabiraman, Nagarajan N.  2006-03-24  Selectivity and potency of cyclin-dependent kinase inhibitors.  [PMID:16584130]

10. DePinto, Wanda W and 19 more authors.  2006-11  In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials.  [PMID:17121911]

11. 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]

12. 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]

13. 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]

14. Gelbert, Lawrence M LM and 16 more authors.  2014-10  Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine.  [PMID:24919854]

15. 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]

16. 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]

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

18. Wang, Yan Y and 10 more authors.  2018-03-01  Design and synthesis of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships.  [PMID:29429832]

19. Tear, Westley F and 16 more authors.  2020-01-23  Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis.  [PMID:31846577]

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

Source

Source(1):

• Scientific Literature