Combination of chemotherapy with dual antagonists and radiotherapy in the treatment of neoplastic disease

Abstract

The theoretical justification for combination chemotherapy and for the combination of radiation and chemotherapy in the treatment of neoplastic diseases is discussed. Literature on the synthesis and biological activity of the 'dual antagonist' group of drugs is reviewed, Studies on the radiation-potentiating effect of certain members of this group of drugs are reviewed, and prospects for therapeutic applications are discussed.

Enantioselective synthesis of aziridines using asymmetric transfer hydrogenation as a precursor for chiral derivatives used as bonding agent for rocket solid propellants

“…The combined organic layers were dried over magnesium sulphate, filtered, and the solvent removed in vacuo. Purification by flash chromatography on silica with ethyl acetate-petroleum ether 40:60, gave the compound as colourless liquid of high viscosity (4 (±) N-(tBoc)-1-aminopropan-2-one (12) (±)-1-Aminopropan-2-ol (11) (1.0 g, 5.71 mmol) was added to an ice cold solution of pyridinium dichromate (6.44 g, 17.13 mmol) in anhydrous N,N-dimethylformamide (20 mL). The reaction mixture was stirred overnight, then worked up with brine (30 mL).…”

“…Among the agents of interest of cancer chemotherapy are the phosphorus aziridines derivatives such as compounds (1), (2) 2 , (3) and (4) 3 . Phosphoaziridines (3) and (4) have been shown in experimental and clinical studies to be potent antitumor agents as well as radiation sensitizers 4 . Some aziridine derivatives are also known as bonding agents for solid propellants which have a high potential to improve the mechanical properties of the propellant grains composed of the fuelbinder, hydroxyl terminated polybutadiene (HTPB) and the solid fillers, ammonium perchlorate (AP) and aluminium powder 5 .…”

Reactions of 2,2-dimethylaziridine-type Alkylating Agents in Biological Systems I: Colorimetric Estimation and Stability in Physiological Media

“…In man, relatively small doses of X-rays produced short-term remissions of solid tumors when administered with Compound I (1417). Furthermore, a recently concluded study of the treatment of bronchogenic carcinoma with this compound in combination with radiotherapy showed some encouraging long-term therapeutic effects (18,19). These results suggest continuing interest in the clinical study of this agent.…”

“…It appears that this drug potentiates the antitumor effects of X-rays clinically (14)(15)(16)(17)(18)(19) as well as in animal experiments (20). In man, relatively small doses of X-rays produced short-term remissions of solid tumors when administered with Compound I (1417).…”

Synthesis of 5'-thymidinyl bis(1-aziridinyl)phosphinates as antineoplastic agents

“…The syntheses of compounds 6-9 were accomplished as outlined in Scheme I. S'-Acetylthymidine (4)10 was converted to the phosphorodichloridate 5; complete removal of the excess phosphorus oxychloride reagent and of the hydrogen chloride byproduct, under high vacuum, was found to be a critical step in the procedure. Compound 5 was then immediately reacted with the appropriate aziridine in the presence of triethylamine to give the 3'-acetyl-blocked title compounds 6 and 7 which were isolated and purified as described under Experimental Section.…”