ethyl 3-(2-(tert-butylamino)-1-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-ynamido)-N-(3,4,5-trifluorobenzyl)benzamido)-2-oxoethyl)-6-chloro-1H-indole-2-carboxylate

ID: ALA4848268

PubChem CID: 164617730

Max Phase: Preclinical

Molecular Formula: C49H44ClF3N6O8

Molecular Weight: 937.37

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: CCOC(=O)c1[nH]c2cc(Cl)ccc2c1C(C(=O)NC(C)(C)C)N(Cc1cc(F)c(F)c(F)c1)C(=O)c1cccc(NC(=O)CCC#Cc2cccc3c2CN(C2CCC(=O)NC2=O)C3=O)c1

Standard InChI: InChI=1S/C49H44ClF3N6O8/c1-5-67-48(66)42-40(32-17-16-29(50)23-36(32)55-42)43(45(63)57-49(2,3)4)59(24-26-20-34(51)41(53)35(52)21-26)46(64)28-12-8-13-30(22-28)54-38(60)15-7-6-10-27-11-9-14-31-33(27)25-58(47(31)65)37-18-19-39(61)56-44(37)62/h8-9,11-14,16-17,20-23,37,43,55H,5,7,15,18-19,24-25H2,1-4H3,(H,54,60)(H,57,63)(H,56,61,62)

Standard InChI Key: RMRIXTBTKDKNDV-UHFFFAOYSA-N

Molfile:

 
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M  END

Associated Targets(Human)

MDM2 Tchem Protein cereblon/E3 ubiquitin-protein ligase Mdm2 (233 Activities)

Discover Target: MDM2

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

CRBN Tclin Cereblon/GSPT1 (159 Activities)

Discover Target: CRBN

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: Unknown	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: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 937.37	Molecular Weight (Monoisotopic): 936.2861	AlogP: 7.25	#Rotatable Bonds: 12
Polar Surface Area: 187.08	Molecular Species: NEUTRAL	HBA: 8	HBD: 4
#RO5 Violations: 2	HBA (Lipinski): 14	HBD (Lipinski): 4	#RO5 Violations (Lipinski): 3
CX Acidic pKa: 10.31	CX Basic pKa: ┄	CX LogP: 6.43	CX LogD: 6.43
Aromatic Rings: 5	Heavy Atoms: 67	QED Weighted: 0.04	Np Likeness Score: -1.08

References

1. Wang B, Liu J, Tandon I, Wu S, Teng P, Liao J, Tang W.. (2021) Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries., 219 [PMID:33862513] [10.1016/j.ejmech.2021.113425]
2. Raboisson, Pierre P and 12 more authors. 2005-04-01 Structure-based design, synthesis, and biological evaluation of novel 1,4-diazepines as HDM2 antagonists. [PMID:15780621]
3. Schneekloth, Ashley R AR, Pucheault, Mathieu M, Tae, Hyun Seop HS and Crews, Craig M CM. 2008-11-15 Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics. [PMID:18752944]
4. Hayashi, Ryo R and 5 more authors. 2009-12-01 N-acylpolyamine inhibitors of HDM2 and HDMX binding to p53. [PMID:19880322]
5. Madden, Michael M and 5 more authors. 2011-03-01 Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition. [PMID:21277201]
6. Ghosh, Pradip P, Zhang, Jiawei J, Shi, Zheng-Zheng ZZ and Li, King K. 2013-04-15 Synthesis and evaluation of an imidazole derivative-fluorescein conjugate. [PMID:23477941]
7. Zhao, Yujun Y and 12 more authors. 2013-07-11 A potent small-molecule inhibitor of the MDM2-p53 interaction (MI-888) achieved complete and durable tumor regression in mice. [PMID:23786219]
8. Blackburn, Tim J and 14 more authors. 2013-09-21 Diaryl- and triaryl-pyrrole derivatives: inhibitors of the MDM2-p53 and MDMX-p53 protein-protein interactions†Electronic supplementary information (ESI) available: Experimental details for compound synthesis, analytical data for all compounds and intermediates. Details for the biological evaluation. Further details for the modeling. Table of combustion analysis data. See DOI: 10.1039/c3md00161jClick here for additional data file. [PMID:24078862]
9. Li, Jin J and 14 more authors. 2014-06-15 Discovery of 1-arylpyrrolidone derivatives as potent p53-MDM2 inhibitors based on molecule fusing strategy. [PMID:24813735]
10. Zheng, Guang-hui GH and 7 more authors. 2014-06-23 Design, synthesis and in vitro and in vivo antitumour activity of 3-benzylideneindolin-2-one derivatives, a novel class of small-molecule inhibitors of the MDM2-p53 interaction. [PMID:24852275]
11. Rew, Yosup Y and 34 more authors. 2014-12-26 Discovery of AM-7209, a potent and selective 4-amidobenzoic acid inhibitor of the MDM2-p53 interaction. [PMID:25384157]
12. Zhao, Yujun Y, Aguilar, Angelo A, Bernard, Denzil D and Wang, Shaomeng S. 2015-02-12 Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment. [PMID:25396320]
13. Aguilar, Angelo and 7 more authors. 2014-12-26 Design of chemically stable, potent, and efficacious MDM2 inhibitors that exploit the retro-mannich ring-opening-cyclization reaction mechanism in spiro-oxindoles. [PMID:25496041]
14. Neochoritis, Constantinos G and 8 more authors. 2015-12-15 2,30-Bis(10H-indole) heterocycles: New p53/MDM2/MDMX antagonists. [PMID:26584879]
15. Daniele, Simona S and 12 more authors. 2016-05-26 Lead Optimization of 2-Phenylindolylglyoxylyldipeptide Murine Double Minute (MDM)2/Translocator Protein (TSPO) Dual Inhibitors for the Treatment of Gliomas. [PMID:27050782]
16. Aguilar, Angelo and 17 more authors. 2017-04-13 Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development. [PMID:28339198]
17. Giustiniano, Mariateresa M and 18 more authors. 2017-10-12 Computer-Aided Identification and Lead Optimization of Dual Murine Double Minute 2 and 4 Binders: Structure-Activity Relationship Studies and Pharmacological Activity. [PMID:28921985]
18. Merlino, Francesco F and 20 more authors. 2018-06-14 Simultaneous Targeting of RGD-Integrins and Dual Murine Double Minute Proteins in Glioblastoma Multiforme. [PMID:29775303]
19. Niazi, Sarfaraj S, Purohit, Madhusudan M and Niazi, Javed H JH. 2018-10-05 Role of p53 circuitry in tumorigenesis: A brief review. [PMID:30199707]
20. Wang, Bo B and 5 more authors. 2019-08-15 Development of selective small molecule MDM2 degraders based on nutlin. [PMID:31128449]
21. Sang, Peng and 10 more authors. 2020-02-13 α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53-MDM2/MDMX Protein-Protein Interactions. [PMID:31971801]

ethyl 3-(2-(tert-butylamino)-1-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)but-3-ynamido)-N-(3,4,5-trifluorobenzyl)benzamido)-2-oxoethyl)-6-chloro-1H-indole-2-carboxylate

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source