Idasanutlin

Base Information

• Chemical Name: Idasanutlin
• CAS No.: 1229705-06-9
• Molecular Formula: C31H29Cl2F2N3O4
• Molecular Weight: 616.492
• European Community (EC) Number: 833-504-1
• UNII: QSQ883V35U
• DSSTox Substance ID: DTXSID001025954
• Nikkaji Number: J3.248.700I
• Wikidata: Q27287480
• NCI Thesaurus Code: C99131
• Pharos Ligand ID: XSJ1QJNXZ9TS
• Metabolomics Workbench ID: 153335
• ChEMBL ID: CHEMBL2402737
• Mol file: 1229705-06-9.mol

Synonyms:idasanutlin;RG7388

Chemical Property of Idasanutlin

Chemical Property:

• Boiling Point: 737.3±60.0 °C(Predicted)
• PKA: 4.11±0.10(Predicted)
• PSA: 114.94000
• Density: 1.40±0.1 g/cm3(Predicted)
• LogP: 7.91718
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 8
• Exact Mass: 615.1503181
• Heavy Atom Count: 42
• Complexity: 1040

Purity/Quality:

99% ^*data from raw suppliers

Idasanutlin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(C)CC1C(C(C(N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F
• Isomeric SMILES: CC(C)(C)C[C@H]1[C@]([C@H]([C@@H](N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F
• Recent ClinicalTrials: Trial of Idasanutlin and Selinexor Therapy for Children With Progressive/Relapsed AT/RT or Extra-CNS Malignant Rhabdoid Tumors
• Recent EU Clinical Trials: A PHASE Ib/II, OPEN-LABEL, MULTICENTER, RANDOMIZED UMBRELLA STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE IMMUNOTHERAPY-BASED TREATMENT COMBINATIONS IN PATIENTS WITH METASTATIC COLORECTAL CANCER (MORPHEUS-CRC)
• Description: Potent MDM2 inhibitor with an IC50 = 6 nM in binding assay and 30 nM in cancer cell proliferation assay. Induces p53 stabilisation, cell cycle arrest and apoptosis in cancer cells expression wildtype p53. Displays inhibition of tumor growth in the SJSA1 tumor xenograft model. Also inhibits MDR-1 at high concentrations.
• Uses: Idasanutlin is an MDM2 inihibtor, blocking the p53 protein-protein interaction and may be used in anti-cancer treatments.

Technology Process of Idasanutlin

There total 22 articles about Idasanutlin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 80.5%

4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino}-3-methoxybenzoic acid methyl ester (1229705-05-8) → 4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid (1229705-06-9)

Guidance literature:

With sodium hydroxide; In tetrahydrofuran; water; at 40 ℃; for 18h;

DOI:10.1021/jm400487c

Reference yield: 45.0%

4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluorophenyl)-3-(3-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)-pyrrolidine-2-carbonyl]amino}-3-methoxybenzoic acid ethyl ester → 4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid (1229705-06-9)

Guidance literature:

With water; lithium hydroxide; In isopropyl alcohol; at 63 - 67 ℃; for 6h; Large scale;

DOI:10.1021/acs.oprd.6b00319

Reference yield: 21.0%

(Z)-3-(3-chloro-2-fluorophenyl)-2-(4-chloro-2-fluorophenyl)prop-2-enenitrile (1219086-87-9) + 4-{2-[3,3-dimethyl-but-(E)-ylideneamino]acetylamino}-3-methoxybenzoic acid methyl ester (1345866-83-2) → 4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid (1229705-06-9)

Guidance literature:

(Z)-3-(3-chloro-2-fluorophenyl)-2-(4-chloro-2-fluorophenyl)prop-2-enenitrile; 4-{2-[3,3-dimethyl-but-(E)-ylideneamino]acetylamino}-3-methoxybenzoic acid methyl ester; With copper diacetate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; triethylamine; In 2-methyltetrahydrofuran; at 20 ℃; for 5h; Inert atmosphere;

With water; sodium hydroxide; In tetrahydrofuran; ethanol; at 20 ℃; for 18h; Inert atmosphere;

upstream raw materials:

(Z)-3-(3-chloro-2-fluorophenyl)-2-(4-chloro-2-fluorophenyl)prop-2-enenitrile

2-[(E)-(3,3-dimethylbutylidene)amino]acetic acid tert-butyl ester

2-(4-chloro-2-fluoro-phenyl)acetonitrile

2-fluoro-3-chlorobenzaldehyde

Downstream raw materials:

2-((1-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)ethoxy)carbonylamino)acetic acid

1-(cyclohexyloxycarbonyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate

Refernces

• 1、 Hansen, Mickel J.,Feringa, Femke M.,Kobauri, Piermichele,Szymanski, Wiktor,Medema, René H.,Feringa, Ben L.. "Photoactivation of MDM2 Inhibitors: Controlling Protein-Protein Interaction with Light". . p. 13136 - 13141. Retrieved 2018/10/20.
• 2、 -. "ASYMMETRIC SYNTHESIS OF A SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDE". Page/Page column 14; 15; 27. . Retrieved 2014/09/03.