Male rats were given cyclophosphamide (50 mg/kg, i.p.), and the plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard were determined. Apparent plasma half-lives were 30 and 55 min, respectively. Area under the plasma concentration-time curve values were 1.5 and 2.5 HIM-min, respectively. Since the plasma half-life of cyclophos phamide in rats is about 37 min, it may be t...

Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed bet...

The 0-24-h urinary metabolic profile of cyclophosphamide was investigated in a series of 14 patients with various malignancies receiving combination chemotherapy including i.v. cyclophosphamide. This was accomplished using combined thin-layer chromatography-photography-densitometry, which can quantitate cyclophosphamide and its four principal urinary metabolites (4-ketocyclophosphamide, nor-nit...

A highly reactive and acidic chiral Brønsted acid catalyst, chiral N-triflyl phosphoramide, was developed. Highly enantioselective Diels-Alder reaction of alpha,beta-unsaturated ketone with silyloxydiene was demonstrated using this chiral Brønsted acid catalyst.

Acquired drug resistance is one of the most important problems in cancer chemotherapy. One of the proposed mechanisms for these phenomena is the sequestration of alkylating agents by metallothionein in vivo. This research shows that metallothionein can covalently sequester phosphoramide mustard, the active form of cyclophosphamide in vitro. On-line electrospray mass spectrometry reveals that it...

Phosphorus-31 NMR spectroscopy was used to analyze urine samples from patients treated with cyclophosphamide (CP) on 2 consecutive days. CP and all of its known phosphorylated metabolites except the tautomeric pair 4-hydroxycyclophosphamide/aldophosphamide, i.e. carboxycyclophosphamide (CXCP), dechloroethylcyclophosphamide (DCCP), alcophosphamide, ketophosphamide, and phosphoramide mustard (PM)...

An organocatalyzed intramolecular carbonyl-ene reaction was developed to produce carbocyclic and heterocyclic 5- and 6-membered rings from a citronellal-derived trifluoroketone and a variety of aldehydes. A phosphoramide derivative was found to promote the cyclization of the trifluoroketone, whereas a less acidic phosphoric acid proved to be a superior catalyst for the aldehyde substrates.

Male rats were given cyclophosphamide (50 mg/kg, i.p.), and the plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard were determined. Apparent plasma half-lives were 30 and 55 min, respectively. Area under the plasma concentration-time curve values were 1.5 and 2.5 HIM-min, respectively. Since the plasma half-life of cyclophos phamide in rats is about 37 min, it may be t...

Cyclophosphamide (CY)-mediated immunoenhancement has been attributed to the inhibition of suppressor T-cell generation. In order to exert its effects on the immune system, metabolic activation of CY is required. The metabolite of CY responsible for its immunoenhancing properties are not known. Two reactive metabolites of CY which may inhibit suppressor T-cell generation are phosphoramide mustar...