N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-7,8,9,10-tetrahydro-6H-benzo[4,5]imidazo[1,2-a]azepin-2-yl)pyrimidin-2-aminee

ID: ALA4204961

PubChem CID: 129102610

Max Phase: Preclinical

Molecular Formula: C28H32F2N8

Molecular Weight: 518.62

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)CCCCC6)n3)nc2)CC1

Standard InChI: InChI=1S/C28H32F2N8/c1-2-36-10-12-37(13-11-36)18-19-7-8-24(31-16-19)33-28-32-17-22(30)26(35-28)20-14-21(29)27-23(15-20)38-9-5-3-4-6-25(38)34-27/h7-8,14-17H,2-6,9-13,18H2,1H3,(H,31,32,33,35)

Standard InChI Key: FLXBKICISVDLQT-UHFFFAOYSA-N

Molfile:

     RDKit          2D

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   15.8158  -12.2512    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.5303  -12.6637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.5303  -13.4887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8158  -13.9013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1014  -13.4888    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.3869  -12.2512    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.4583  -12.5062    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.9433  -11.8387    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7674  -11.8017    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.3102  -12.4230    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.1569  -13.2240    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.4424  -13.6365    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.6778  -13.3015    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4583  -11.1713    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
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   17.9592  -10.1887    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   17.2448  -13.9013    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.6724  -12.6637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6724  -13.4887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9579  -13.9012    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2435  -13.4887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2435  -12.6637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9579  -12.2512    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.5290  -13.9012    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8145  -13.4887    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
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    9.3856  -13.4887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3856  -12.6637    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.1001  -12.2512    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    8.6711  -12.2512    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9566  -12.6637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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  7 24  1  0
M  END

Associated Targets(Human)

CDK4 Tclin Cyclin-dependent kinase 4 (2749 Activities)

Discover Target: CDK4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CDK1 Tchem Cyclin-dependent kinase 1/ G1/S-specific cyclin-D3 (24 Activities)

Discover Target: CDK1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CDK6 Tclin Cyclin-dependent kinase 6 (1724 Activities)

Discover Target: CDK6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

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

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: 518.62	Molecular Weight (Monoisotopic): 518.2718	AlogP: 4.77	#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: 7.94	CX LogP: 4.76	CX LogD: 4.10
Aromatic Rings: 4	Heavy Atoms: 38	QED Weighted: 0.39	Np Likeness Score: -1.47

References

1. Wang Y, Liu WJ, Yin L, Li H, Chen ZH, Zhu DX, Song XQ, Cheng ZZ, Song P, Wang Z, Li ZG.. (2018) 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., 28 (5): [PMID:29429832] [10.1016/j.bmcl.2017.12.068]
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]

N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-7,8,9,10-tetrahydro-6H-benzo[4,5]imidazo[1,2-a]azepin-2-yl)pyrimidin-2-aminee

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source