Idarubicin

Solid

Solid

Idarubicin is a monosaccharide derivative, an anthracycline antibiotic and a deoxy hexoside. It derives from a hydride of a tetracene.|An orally administered anthracycline antineoplastic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with the potential for reduced cardiac toxicity.|Idarubicin is an Anthracycline Topoisomerase Inhibitor. The mechanism of action of idarubicin is as a Topoisomerase Inhibitor.|Doxorubicin, epirubicin, idarubicin and valrubicin are structurally related cytotoxic antineoplastic antibiotics used in the therapy of several forms of lymphoma, leukemia, sarcoma and solid organ cancers. Doxorubicin is associated with a high rate of transient serum enzyme during therapy and to rare instances of clinically apparent acute liver injury with jaundice that can be severe and even fatal. Epirubicin and idarubicin have similar profiles of activity and adverse events as doxorubicin, but have been less commonly used and their potential for causing liver injury has been less well defined. Valrubicin is instilled directly in the bladder as treatment of refractory urinary bladder cancer, has little systemic distribution, and has not been associated with serum enzyme elevations or clinically apparent liver injury.|Idarubicin is a semisynthetic 4-demethoxy analogue of the antineoplastic anthracycline antibiotic daunorubicin. Idarubicin intercalates into DNA and interferes with the activity of topoisomerase II, thereby inhibiting DNA replication, RNA transcription and protein synthesis. Due to its high lipophilicity, idarubicin penetrates cell membranes more efficiently than other anthracycline antibiotic compounds.|An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA.

Suspend compound ((-)-II) (159mg, 0.29mmo1) and 0.8g4A molecular sieve in a mixture of 12ml dichloromethane and 10ml ether under the protection of -40℃ and argon, add TMSOTf (0.12ml, 0.62mmo1) ). Stir at 0°C for 1 h. Cool to -15°C, add compound (+)-(I) (85mg, 0.23mmol) dissolved in 25ml of dichloromethane, and stir at -15°C for 5h. Under vigorous stirring, the reaction solution was poured into a mixture of 150 ml saturated sodium bicarbonate and 80 ml ethyl acetate. The organic layer was separated, washed with saturated brine (2×50 ml), and dried with anhydrous magnesium sulfate. After filtration, the filtrate was concentrated in vacuo, and the remaining solution was passed through a short silica gel column and eluted with ethyl acetate-benzene (1:4). 170 mg of compound (-)-(Ⅲ) was obtained, and the yield was 99.5%. Compound (-)-(Ⅲ) (189.0 mg, 0.25 mmol) was dissolved in 1.5 ml of dichloromethane, and 2.5 ml of 0.1 mol/L sodium hydroxide solution was added at 0°C under stirring and under argon protection. Stir at 0°C for 30 min. Add glacial acetic acid until the solution becomes bright orange, then add 150ml ethyl acetate and 150ml saturated brine. The organic layer was separated, washed with saturated brine (2×50 ml), and dried with anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with dichloromethane-acetone (9:1). 120 mg of compound (+)-(1V) was obtained, the yield was 83%, the melting point was 151-153°C, [α]D20+190° (C=0.10, dioxane). Compound (+)-(IV) (95.7 mg, 0.17 mmol) was dissolved in 20 ml of 0.1 mol/L sodium hydroxide solution, and stirred at room temperature under argon protection for 20 min. After adjusting to Ph=8 with 5mol/L hydrochloric acid, it was extracted with chloroform until the extract was no longer orange (about 5×70ml). The extracts were combined, washed with 50 ml of water, and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue is dissolved in a small amount of chloroform and methanol (9:1) mixed solution, 0.25mol/L hydrogen chloride methanol solution is added to Ph=3-5, and then 30ml ether is added. 69.7mg of orange powdered idarubicin hydrochloride can be obtained with a yield of 77%.

Inhibit tumor growth and fight breast cancer.

Molecular Weight:497.5
XLogP3:1.9
Hydrogen Bond Donor Count:5
Hydrogen Bond Acceptor Count:10
Rotatable Bond Count:3
Exact Mass:497.16858144
Monoisotopic Mass:497.16858144
Topological Polar Surface Area:177
Heavy Atom Count:36
Complexity:912
Defined Atom Stereocenter Count:6
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes