4-(1-ethyl-5-fluoro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)-5-fluoro-N-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-yl)pyrimidin-2-amine

ID: ALA4217694

PubChem CID: 129102600

Max Phase: Preclinical

Molecular Formula: C27H30F2N8

Molecular Weight: 504.59

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CCC1CCc2nc3c(F)cc(-c4nc(Nc5ccc(CN6CCN(C)CC6)cn5)ncc4F)cc3n21

Standard InChI:  InChI=1S/C27H30F2N8/c1-3-19-5-7-24-33-26-20(28)12-18(13-22(26)37(19)24)25-21(29)15-31-27(34-25)32-23-6-4-17(14-30-23)16-36-10-8-35(2)9-11-36/h4,6,12-15,19H,3,5,7-11,16H2,1-2H3,(H,30,31,32,34)

Standard InChI Key:  YASYFVUJCWYQTN-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 37 42  0  0  0  0  0  0  0  0999 V2000
   18.2217  -15.7768    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.6073  -17.5664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7494  -17.5664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6086  -16.3289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1797  -16.3289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3205  -17.5664    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.3432  -13.8037    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6060  -17.1539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.9232  -14.1842    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4639  -18.8039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6086  -17.1539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6073  -18.3914    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8929  -17.1539    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.0350  -18.8039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4652  -18.3914    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3231  -17.5664    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   17.0657  -15.1094    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.8942  -15.9164    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7507  -17.1539    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.8929  -18.8039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7494  -18.3914    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.1797  -17.1539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8862  -15.0232    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7301  -14.3557    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1797  -18.8039    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   15.4652  -17.5664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7507  -18.8039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8942  -17.5664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6682  -13.3996    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0363  -18.3914    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.1784  -17.5664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1784  -18.3914    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.0577  -14.2162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0363  -17.5664    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3205  -18.3914    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0350  -17.1539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3218  -17.1539    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  2 13  2  0
 26 15  1  0
 33  7  1  0
 21  3  1  0
 10 21  1  0
 26 22  1  0
 11 16  1  0
  4 11  2  0
 23  1  2  0
 22 28  2  0
 31 13  1  0
 15 27  2  0
 19 26  2  0
 35  6  1  0
  2 12  1  0
  4 18  1  0
 14 35  1  0
 21 14  1  0
 28 11  1  0
 32 31  2  0
  9 29  1  0
  5 22  1  0
 18 17  1  0
 23 33  1  0
 32 10  1  0
 12 20  2  0
  1  4  1  0
 34 37  1  0
 24  9  1  0
 27 30  1  0
 18  5  2  0
  6 36  1  0
 23 17  1  0
  6  8  1  0
 37  2  1  0
 15 25  1  0
 34 30  2  0
 34 19  1  0
 17 24  1  0
 20 32  1  0
  7 24  1  0
 36  3  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4217694

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 504.59

Molecular Weight (Monoisotopic): 504.2561

AlogP: 4.55

#Rotatable Bonds: 6

Polar Surface Area: 75.00

Molecular Species: NEUTRAL

HBA: 8

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 10.27

CX Basic pKa: 7.70

CX LogP: 4.45

CX LogD: 3.97

Aromatic Rings: 4

Heavy Atoms: 37

QED Weighted: 0.41

Np Likeness Score: -1.34

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. Leost, M M and 14 more authors.  2000-10  Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25.  [PMID:10998059]

4. 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]

5. Bramson, H N HN and 20 more authors.  2001-12-06  Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.  [PMID:11728181]

6. Mettey, Yvette Y and 9 more authors.  2003-01-16  Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects.  [PMID:12519061]

7. Ring, David B DB and 12 more authors.  2003-03  Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo.  [PMID:12606497]

8. Sayle, Kerry L KL and 16 more authors.  2003-09-15  Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2.  [PMID:12941338]

9. Kuo, Gee-Hong GH and 13 more authors.  2005-03-24  Synthesis and discovery of pyrazine-pyridine biheteroaryl as a novel series of potent vascular endothelial growth factor receptor-2 inhibitors.  [PMID:15771433]

10. Lin, Ronghui R and 11 more authors.  2005-06-30  1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.  [PMID:15974571]

11. 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]

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

13. 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]

14. 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]

15. Jones, Clifford D CD and 18 more authors.  2008-12-15  The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing.  [PMID:18996007]

16. 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]

17. 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]

18. 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]

19. 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]

20. 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]

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

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

23. 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]

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Source

Source(1):

• Scientific Literature