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-(8-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)octyl)acetamide

ID: ALA4448920

PubChem CID: 155520334

Max Phase: Preclinical

Molecular Formula: C47H57N11O7

Molecular Weight: 888.04

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CC(=O)NCCCCCCCCNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O

Standard InChI:  InChI=1S/C47H57N11O7/c1-29-34-27-51-47(54-42(34)57(31-12-7-8-13-31)45(64)40(29)30(2)59)52-37-18-16-32(26-50-37)56-24-22-55(23-25-56)28-39(61)49-21-10-6-4-3-5-9-20-48-35-15-11-14-33-41(35)46(65)58(44(33)63)36-17-19-38(60)53-43(36)62/h11,14-16,18,26-27,31,36,48H,3-10,12-13,17,19-25,28H2,1-2H3,(H,49,61)(H,53,60,62)(H,50,51,52,54)

Standard InChI Key:  JWWJOXYINXWNGC-UHFFFAOYSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4448920

   ---

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: 888.04

Molecular Weight (Monoisotopic): 887.4442

AlogP: 4.65

#Rotatable Bonds: 18

Polar Surface Area: 220.93

Molecular Species: NEUTRAL

HBA: 15

HBD: 4

#RO5 Violations: 2

HBA (Lipinski): 18

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.15

CX Basic pKa: 6.22

CX LogP: 4.37

CX LogD: 4.34

Aromatic Rings: 4

Heavy Atoms: 65

QED Weighted: 0.06

Np Likeness Score: -1.01

References

1. Rana S, Bendjennat M, Kour S, King HM, Kizhake S, Zahid M, Natarajan A..  (2019)  Selective degradation of CDK6 by a palbociclib based PROTAC.,  29  (11): [PMID:30935795] [10.1016/j.bmcl.2019.03.035]

2. 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]

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. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. Zhi, Yanle Y and 9 more authors.  2018-07-15  Discovery of the selective and efficacious inhibitors of FLT3 mutations.  [PMID:29894944]

Source

Source(1):

• Scientific Literature