65026-79-1Relevant articles and documents
Adriamycin Analogues. Rationale, Synthesis, and Preliminary Antitumor Evaluation of Highly Active DNA-Nonbinding N-(Trifluoroacetyl)adriamycin 14-O-Hemiester Derivatives
Israel, Mervyn,Potti, P. Gopalakrishnan,Seshadri, Ramakrishnan
, p. 1223 - 1228 (1985)
N-(Trifluoroacetyl)adriamycin 14-valerate (AD 32), a novel DNA nonbinding analogue of adriamycin with superior experimental antitumor activity, has undergone extensive clinical trial, with documentation of antitumor activity and low toxicity in human subjects.However, poor water solubility necessitates that the drug be administered to patients by continuous intravenous infusion at high dilution in a surfactant-containing formulation, with steroid prophylaxis to protect against a chest pain syndrome associated with the vehicle.On the basis of pharmacologic considerations, the title compounds have been prepared as second-generation analogues of N-(trifluoroacetyl)adriamycin 14-valerate with improved aqueous solubility; use is made of the available carboxylic acid function to solubilize the products in dilute aqueous alkaline medium.Target compounds were made by treating N-(trifluoroacetyl)-14-halodaunorubicin (bromo or iodo) with monosodium salts of dibasic acids (malonic, succinic, glutaric, adipic, pimelic, azelaic, sebacic) in aqueous acetone.All of the products showed significant in vivo antitumor activity against the murine P388 leukemia (ip tumor, ip treatment once daily on days 1, 2, 3, and 4); most compounds were superior to the +181percent increase in life span afforded by adriamycin (optimal dose 3.0 mg/kg per day), one of two drugs used as positive controls for the assays.Several of the test compounds showed highly curative activity in this system, similar to N-(trifluoroacetyl)adriamycin 14-valerate, the other positive control agent.The hemiadipate product exhibited the most desirable properties of high antitumor efficacy (86percent cure rate of all P388 tumor-bearing animals through four levels of a 40-70 mg/kg dose-response range), aqueous solubility (60 mg/mL in pH 7.4 phosphate buffer), and solution stability (no decomposition at 4 deg C, 0.5percent hydrolysis at 27 deg C, over 24 h at pH 7.4).
Synthetic method for valrubicin
-
, (2018/09/21)
The invention discloses a synthetic method for valrubicin. The synthetic method comprises the following steps: subjecting daunorubicin hydrochloride to a bromination reaction, with the carbonyl groupof the daunorubicin hydrochloride being under the protection of triethyl orthoformate, subjecting an obtained reaction solution to concentration treatment, then directly subjecting a concentrated solution to a deprotection reaction, carrying out salt-induced precipitation after completion of the deprotection reaction so as to crystallize a bromide intermediate, allowing the crystallized bromide intermediate to react with potassium n-pentanoate, and carrying out a reaction with trifluoroacetic anhydride to form an amide so as to prepare valrubicin. The synthetic method provided by the inventionhas the advantages of mild reaction conditions, short reaction time, easiness in operation and control, and applicability to large-scale industrial production.
PRODRUGS ACTIVATED BY CASPASE
-
Paragraph 0120, (2016/06/13)
Described are prodrug conjugates that release a chemotherapeutic agent upon activation by caspase, and methods using such prodrug conjugates to induce apoptosis, amplify apoptosis, and treat cancer.
