Amrubicin

Base Information

• Chemical Name: Amrubicin
• CAS No.: 110267-81-7
• Molecular Formula: C₂₅H₂₅NO₉
• Molecular Weight: 483.475
• UNII: 93N13LB4Z2
• Nikkaji Number: J361.794G
• Wikipedia: Amrubicin
• Wikidata: Q4748723
• NCI Thesaurus Code: C80089
• Metabolomics Workbench ID: 149712
• ChEMBL ID: CHEMBL1186894
• Mol file: 110267-81-7.mol

Synonyms:(+)-(7S,9S)-9-acetyl-9-amino-7-((2-deoxy-beta-d-erythro-pentopyranosyl)oxy)-6,11-dihydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione hydrochloride;(7S,9S)-9-acetyl-9-amino-7-((2-deoxy-beta-D-erythro-pentopyranosyl)oxy)-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-naphthacenedione hydrochloride;amrubicin;amrubicin hydrochloride;SM 5887;SM-5887

Chemical Property of Amrubicin

Chemical Property:

• Vapor Pressure: 1.26E-21mmHg at 25°C
• Melting Point: 172-174 °C
• Refractive Index: 1.72
• Boiling Point: 717.8 °C at 760 mmHg
• PKA: 7.83±0.60(Predicted)
• Flash Point: 387.9 °C
• PSA: 176.61000
• Density: 1.6 g/cm³
• LogP: 1.33210
• XLogP3: 0.9
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 3
• Exact Mass: 483.15293138
• Heavy Atom Count: 35
• Complexity: 881

Purity/Quality:

99% ^*data from raw suppliers

Amrubicin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(=O)C1(CC(C2=C(C1)C(=C3C(=C2O)C(=O)C4=CC=CC=C4C3=O)O)OC5CC(C(CO5)O)O)N
• Isomeric SMILES: CC(=O)[C@]1(C[C@@H](C2=C(C1)C(=C3C(=C2O)C(=O)C4=CC=CC=C4C3=O)O)O[C@H]5C[C@@H]([C@@H](CO5)O)O)N
• Recent ClinicalTrials: Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer
• Recent EU Clinical Trials: A Randomized, Open-Label, Multinational Phase 3 Trial Comparing Amrubicin Versus Topotecan in Patients With Extensive or Limited and Sensitive or Refractory Small Cell Lung Cancer After Failure of First-Line Chemotherapy
• Recent NIPH Clinical Trials: A phase III study of ONO-4538/BMS-936558(CA209331/ONO-4538-26)
• Description: Amrubicin is an active agent for the treatment of small-cell lung cancer (SCLC). It is a type of anthracycline analog. Anthracycline derivatives such as doxorubicin (DXR), daunorubicin (DNR) and epirubicin have been widely used for a variety of carcinomas in the clinical context. Amrubicin is structurally distinguishable from other anthracyclines by the amino group at the 9-position and its unique sugar moiety. In April 2002, Amrubicin was approved in Japan for the treatment of non-small cell lung cancer and small cell lung cancer.
• Uses: Synthetic anthracycline antibiotic; inhibits DNA topoisomerase II. Antineoplastic. Amrubicin is used to treat small-cell lung cancer (SCLC).

Technology Process of Amrubicin

There total 26 articles about Amrubicin 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: 90.0%

(+)-9-amino-4-demethoxy-9-deoxy-7-O-(2-deoxy-3,4-di-O-acetyl-β-D-erythro-pentopyranosyl)daunomycinone (110267-80-6) → Amrubicin (110267-81-7)

Guidance literature:

With potassium carbonate; In methanol; dichloromethane; at -5 ℃; for 18h;

DOI:10.1021/jo00229a010

Reference yield:

(R)-(-)-9-acetyl-9-acetamido-6,11-dihydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione (104319-02-0) → Amrubicin (110267-81-7)

Guidance literature:

Multi-step reaction with 5 steps

1: 88 percent / p-toluenesulfonic acid / toluene / 4 h / Heating

2: 88.5 percent / 1,3-dibromo-5,5-dimethylhydantoin / benzene / 0.25 h / Heating; Irradiation

3: 81.8 percent / 3 N aq. H₂SO₄ / 30 h / 80 °C

4: 86 percent / tetramethylurea, silver trifluoromethanesulfonate / CH₂Cl₂; diethyl ether / 0.5 h / 0 - 5 °C

5: 90 percent / potassium carbonate / methanol; CH₂Cl₂ / 18 h / -5 °C

With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; sulfuric acid; silver trifluoromethanesulfonate; potassium carbonate; toluene-4-sulfonic acid; tetramethylurea; In methanol; diethyl ether; dichloromethane; toluene; benzene;

DOI:10.1021/jo00229a010

Reference yield:

5,8-dimethoxy-2-tetralone (37464-90-7) → Amrubicin (110267-81-7)

Guidance literature:

Multi-step reaction with 13 steps

1: 98.7 percent / ammonium carbonate / ethanol; H₂O / 1 h / Heating

2: 92 percent / barium hydroxide octahydrate / H₂O / 36 h / Heating

3: 94.9 percent / HCl (g) / 24 h / 25 °C

5: 1.) sodium hydride / 1.) THF, 65 deg C, 1.5 h, 2.) THF, 5 deg C - 10 deg C, 1 h

6: aq. sodium hydroxide, zinc / toluene / 2 h / 65 °C

7: pyridine / 1.) 20 deg C, 1 h, 2.) 70 deg C, 30 min

8: 90 percent / sodium chloride, aluminum chloride / 0.07 h / 170 °C

9: 88 percent / p-toluenesulfonic acid / toluene / 4 h / Heating

10: 88.5 percent / 1,3-dibromo-5,5-dimethylhydantoin / benzene / 0.25 h / Heating; Irradiation

11: 81.8 percent / 3 N aq. H₂SO₄ / 30 h / 80 °C

12: 86 percent / tetramethylurea, silver trifluoromethanesulfonate / CH₂Cl₂; diethyl ether / 0.5 h / 0 - 5 °C

13: 90 percent / potassium carbonate / methanol; CH₂Cl₂ / 18 h / -5 °C

With pyridine; ammonium carbonate; hydrogenchloride; sodium hydroxide; aluminium trichloride; barium hydroxide octahydrate; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; sulfuric acid; silver trifluoromethanesulfonate; sodium hydride; potassium carbonate; toluene-4-sulfonic acid; tetramethylurea; sodium chloride; zinc; In methanol; diethyl ether; ethanol; dichloromethane; water; toluene; benzene;

DOI:10.1021/jo00229a010

upstream raw materials:

(+)-9-amino-4-demethoxy-9-deoxy-7-O-(2-deoxy-3,4-di-O-acetyl-β-D-erythro-pentopyranosyl)daunomycinone

5,8-dimethoxy-2-tetralone

Acetic acid (3R,4S)-4-acetoxy-6-bromo-tetrahydro-pyran-3-yl ester

2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid

Refernces

• 1、 Ishizumi, Kikuo,Ohashi, Naohito,Tanno, Norihiko. "Stereospecific Total Synthesis of 9-Aminoanthracyclines: (+)-9-Amino-9-deoxydaunomycin and Related Compounds". . p. 4477 - 4485. Retrieved 2007/10/02.