Biomaterial Database

Effect of aminomethyl (N-Mannich base) derivatization on the ability of S6-acetyloxymethyl-6-mercaptopurine prodrug to deliver 6-mercaptopurine through hairless mouse skin. 1990

A N Saab, and K B Sloan, and H D Beall, and R Villaneuva

Department of Medicinal Chemistry, University of Florida, Gainesville 32610.

A series of 9-aminomethyl-S6-acetyloxymethyl-6-mercaptopurine (9-AM-6-AOM-6-MP) prodrugs have been synthesized and characterized, and their ability to deliver total 6-mercaptopurine (6-MP) through hairless mouse skin has been measured. The 9-AM-6-AOM-6-MP prodrugs are much more soluble in isopropyl myristate (IPM) than S6-acetyloxymethyl-6-MP (6-AOM-6-MP) itself or the corresponding 7-aminomethyl-6-MP (7-AM-6-MP) prodrugs. The 9-AM-6-AOM-6-MP prodrugs were all more effective (1.8-4 times) than 6-AOM-6-MP at delivering total 6-MP, except for the piperidylmethyl derivative which only gave a comparable rate of delivery. The 9-AM-6-AOM-6-MP prodrugs were also more effective (7-27 times) than the corresponding 7-AM-6-MP prodrugs at delivering 6-MP, except for the diethylaminomethyl derivative which only gave a comparable rate of delivery. In contrast to the 9-aminomethyl-S6-pivaloyloxymethyl-6-MP (9-AM-6-POM-6-MP) derivatives which generally delivered as much or more intact S6-pivaloyloxymethyl-6-MP (6-POM-6-MP) as 6-MP, the 9-AM-6-AOM-6-MP derivatives delivered mainly (80-95%) 6-MP from IPM. There was a direct correlation between log experimental permeability coefficients for delivery of total 6-MP (P sigma) and the calculated solubility parameter values for the 9-AM-6-AOM-6-MP prodrugs(delta j), with the P sigma generally decreasing as the value of delta j approached that of the vehicle, IPM.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008812	Mice, Hairless	Mutant strains of mice that produce little or no hair.	Hairless Mice,Mice, Inbred HRS,Mice, hr,Hairless Mouse,Mice, HRS,Mouse, HRS,Mouse, Inbred HRS,HRS Mice,HRS Mice, Inbred,HRS Mouse,HRS Mouse, Inbred,Inbred HRS Mice,Inbred HRS Mouse,Mouse, Hairless
D011355	Prodrugs	A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.	Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012869	Skin Absorption	Uptake of substances through the SKIN.	Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions
D015122	Mercaptopurine	An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.	6-Mercaptopurine,1,7-Dihydro-6H-purine-6-thione,6-Mercaptopurine Monohydrate,6-Thiohypoxanthine,6-Thiopurine,6H-Purine-6-thione, 1,7-dihydro-,BW 57-323H,Leupurin,Mecaptopurine Anhydrous,Mercaptopurina Wellcome,Puri-Nethol,Purimethol,Purinethol,6 Mercaptopurine,6 Mercaptopurine Monohydrate,6 Thiohypoxanthine,6 Thiopurine,BW 57 323H,BW 57323H
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus