2,4,6-トリス(1-アジリジニル)-1,3,5-トリアジン

Log P= -0.54

-0.2

MINUTE CRYSTALS FROM CHLOROFORM

WHITE, CRYSTALLINE POWDER

less than 1 mg/mL at 61 °F (NTP, 1992)

WT/WT @ 26 °C: WATER 40%, CHLOROFORM 28.1%, METHYLENE CHLORIDE 19.7%, DIOXANE 9.6%, ETHANOL 7.7%, DIMETHYL CELLOSOLVE 4.8%, ETHYL ACETATE 4.5%, CARBON TETRACHLORIDE 3.6%, ACETONE 10.6%, METHYL ETHYL KETONE 4.7%, METHANOL 12.5%, BENZENE 5.6%

Soluble in oxygenated and chlorinated solvents.

282 °F (decomposes) (NTP, 1992)

@ 160 °C, IT INITIALLY MELTS, THEN RAPIDLY POLYMERIZES TO WHITE SOLID

SYMPTOMS: Symptoms of exposure to this compound may include burning in the throat, vomiting, watery to bloody diarrhea, abdominal pain, oliguria, fall in blood pressure, anuria, cardiovascular collapse, delirium, convulsions, muscular weakness with respiratory failure, and lymphopenia. Other symptoms may include gastrointestinal disturbances and bone marrow depression.

TRIETHYLENEMELAMINE polymerizes readily with heat or moisture. Neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides.

URINE FROM CANCER PT TREATED WITH LABELLED TEM CONTAINED 14 RADIOACTIVE METABOLITES. APPROX 8% OF RADIOACTIVITY EXCRETED IN URINE WAS IN UREA & CREATININE; NO UNCHANGED DRUG DETECTED.

IN MICE INJECTED IP WITH 9 MG/KG BODY WT TEM IN WHICH AZIRIDINE RINGS WERE LABELLED WITH (14)C...16 RADIOACTIVE METABOLITES WERE FOUND; ONLY ONE, CREATININE, WAS IDENTIFIED.

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)

IT IS LESS WELL ABSORBED FROM THE GI TRACT THAN FROM THE PERITONEAL CAVITY. ... BLOOD LEVELS OF TEM FALL RAPIDLY AFTER IV INJECTION IN MAN, THE CONCN BEING ONLY 10% OF THE EXPECTED VALUE 2 MIN AFTER ADMIN. THE IS NO PERSISTENT SELECTIVE UPTAKE BY ANY TISSUE.

FOLLOWING IP ADMIN TO MICE OF TEM LABELLED WITH (14)C IN TRIAZINE RING, MOST OF ACTIVITY WAS EXCRETED IN URINE WITHIN 24 HR... IN MICE INJECTED IP...IN WHICH AZIRIDINE RINGS WERE LABELLED WITH (14)C, ABOUT 70% OF ADMIN RADIOACTIVITY WAS EXCRETED IN URINE WITHIN FIRST 24 HR...

PATIENT WITH ACUTE LYMPHATIC LEUKEMIA WAS GIVEN TEM LABELLED WITH (14)C IN AZIRIDINE RING IV @ DOSE OF 2 MG ... OVER 90% OF RADIOACTIVITY DISAPPEARED FROM BLOOD WITHIN 5 MIN. ... PATIENT WITH METASTASIZING EPIDERMAL CARCINOMA, 3 MG OF DRUG ... ORALLY. IN BOTH CASES 25-30% OF ADMIN ACTIVITY ... EXCRETED IN URINE ... WITHIN FIRST 48 HR ... .

FOLLOWING ITS IV INJECTION IN MICE @...0.8 MG/KG BODY WT OR IN OSBORNE-MENDEL RATS @...0.11 & 0.13 MG/KG BODY WT, TEM DISAPPEARED RAPIDLY FROM BLOOD: WITHIN 10 MIN LEVEL HAD FALLEN TO LESS THAN 10% OF ORIGINAL ACTIVITY.