202350-68-3

Basic information

• Product Name: PNU-159682
• Synonyms: PNU-159682;PNU-159682 95%;PNU-159682 >95%;(8S,10S)-7,8,9,10-Tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-10-[[(1S,3R,4aS,9S,9aR,10aS)-octahydro-9-methoxy-1-methyl-1H-pyrano[4',3':4,5]oxazolo[2,3-c][1,4]oxazin-3-yl]oxy]-5,12-naphthacenedione
• CAS NO: 202350-68-3
• Molecular Formula: C₃₂H₃₅NO₁₃
• Molecular Weight: 641.6192
• Mol File: 202350-68-3.mol

Chemical Properties

• Boiling Point: 838.5±65.0 °C(Predicted)
• Appearance: /
• Density: 1.58±0.1 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 7.34±0.60(Predicted)
• CAS DataBase Reference: PNU-159682(CAS DataBase Reference)
• NIST Chemistry Reference: PNU-159682(202350-68-3)
• EPA Substance Registry System: PNU-159682(202350-68-3)

Safety Data

• Hazardous Substances Data: 202350-68-3(Hazardous Substances Data)

Usage

Characteristics

PNU-159682, a metabolite of the anthracycline neomycin metabolite, is a DNA topoisomerase I (TopoI) inhibitor with excellent cytotoxicity. It is a more potent and tolerable ADC cytotoxin than doxorubicin in ADC synthesis.

Uses

PNU-159682 can be used in EDV nanocell technology to overcome drug resistance.

Upstream product

• 108943-08-4 3'-deamino-3'-[2''(S)-methoxy-4''-morpholinyl]doxorubicin hydrochloride 
• 179484-51-6 C₃₂H₃₇NO₁₄ 

Downstream Products

• 1204819-81-7 ethyl [(1-{2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4-{[(1S,3R,4aS,9S,9aR,10aS)-9-methoxy-1-methyloctahydro-1H-pyrano[4',3':4,5][1,3]oxazolo[2,3-c][1,4]oxazin-3-yl]oxy}6,11-dioxo-1,2,3,4,6,11-hexahydrotetracene-2-yl]ethoxy}cyclohexyl)oxy]acetate 

Relevant articles and documents

In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: A comparison with human liver microsomes

We recently demonstrated that nemorubicin (MMDX), an investigational antitumor drug, is converted to an active metabolite, PNU-159682, by human liver cytochrome P450 (CYP) 3A4. The objectives of this study were: (1) to investigate MMDX metabolism by liver microsomes from laboratory animals (mice, rats, and dogs of both sexes) to ascertain whether PNU-159682 is also produced in these species, and to identify the CYP form(s) responsible for its formation; (2) to compare the animal metabolism of MMDX with that by human liver microsomes (HLMs), in order to determine which animal species is closest to human beings; (3) to explore whether differences in PNU-159682 formation are responsible for previously reported species- and sex-related differences in MMDX host toxicity. The animal metabolism of MMDX proved to be qualitatively similar to that observed with HLMs since, in all tested species, MMDX was mainly converted to PNU-159682 by a single CYP3A form. However, there were marked quantitative inter- and intra-species differences in kinetic parameters. The mouse and the male rat exhibited Vmax and intrinsic metabolic clearance (CLint) values closest to those of human beings, suggesting that these species are the most suitable animal models to investigate MMDX biotransformation. A close inverse correlation was found between MMDX CLint and previously reported values of MMDX LD50 for animals of the species, sex and strain tested here, indicating that differences in the in vivo toxicity of MMDX are most probably due to sex- and species-related differences in the extent of PNU-159682 formation.

Method for preparing drug toxin PNU-159682of antibody conjugated drug, and intermediate involved in preparation method

The invention provides a method for preparing a drug toxin PNU-159682 (morpholinyl anthracycline derivative) of an antibody conjugated drug, and an intermediate involved in the preparation method. According to the preparation method, by introducing a protective group and using an easily-amplified reagent, the stability, the practicability and the amplifiability of the process are improved; and with the preparation method, the risk and the operation difficulty during large-scale production are reduced, and the preparation production operation is simple and convenient.

PROCESS FOR THE PREPARATION OF MORPHOLINYL ANTHRACYCLINE DERIVATIVES

The present invention provides a process for the preparation of a morpholinyl anthracycline derivative in good yields and purity, including 3'-deamino-3"-4'-anhydro- [2"(S)-methoxy-3"(R)-hydroxy-4"-morpholinyl] doxorubicin (1).