2-(2,6-dioxopiperidin-3-yl)-4-(2-(2-(4-((4-((6-(5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-ylamino)pyridin-3-yl)methyl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethylamino)isoindoline-1,3-dione

ID: ALA4590483

PubChem CID: 155567647

Max Phase: Preclinical

Molecular Formula: C45H48F2N14O5

Molecular Weight: 902.97

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1nc2c(F)cc(-c3nc(Nc4ccc(CN5CCN(Cc6cn(CCOCCNc7cccc8c7C(=O)N(C7CCC(=O)NC7=O)C8=O)nn6)CC5)cn4)ncc3F)cc2n1C(C)C

Standard InChI:  InChI=1S/C45H48F2N14O5/c1-26(2)60-27(3)51-41-32(46)19-29(20-36(41)60)40-33(47)22-50-45(54-40)52-37-9-7-28(21-49-37)23-57-12-14-58(15-13-57)24-30-25-59(56-55-30)16-18-66-17-11-48-34-6-4-5-31-39(34)44(65)61(43(31)64)35-8-10-38(62)53-42(35)63/h4-7,9,19-22,25-26,35,48H,8,10-18,23-24H2,1-3H3,(H,53,62,63)(H,49,50,52,54)

Standard InChI Key:  HYZNVNZFNOPQLO-UHFFFAOYSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4590483

   ---

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: 902.97

Molecular Weight (Monoisotopic): 902.3900

AlogP: 4.24

#Rotatable Bonds: 16

Polar Surface Area: 210.52

Molecular Species: NEUTRAL

HBA: 17

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 19

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 10.25

CX Basic pKa: 6.43

CX LogP: 3.83

CX LogD: 3.78

Aromatic Rings: 6

Heavy Atoms: 66

QED Weighted: 0.09

Np Likeness Score: -1.40

References

1. Su S, Yang Z, Gao H, Yang H, Zhu S, An Z, Wang J, Li Q, Chandarlapaty S, Deng H, Wu W, Rao Y..  (2019)  Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders.,  62  (16): [PMID:31330105] [10.1021/acs.jmedchem.9b00871]

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