Topical delivery of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of theophylline (ThH).
N(7)-(N-Alkyl-N-alkyloxycarbonyl) aminomethyl (NANAOCAM) prodrugs of theophylline (ThH) have been synthesized and characterized by their solubilities in isopropyl myristate (S(IPM)), solubilities in water (S(AQ)), partition coefficients between IPM and pH 4.0 buffer (K(IPM:4.0)) and by their ability to penetrate hairless mouse skin from IPM (J(MIPM)). The most lipid soluble and water soluble member, N-methyl-N-ethyloxy-carbonylaminomethyltheophylline, gave the highest flux through hairless mouse skin from IPM compared to ThH. The flux of NANAOCAM prodrugs of ThH can be accurately predicted by the Roberts-Sloan (RS) equation.
Majumdar
Susruta
S
Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA.
Sloan
K B
KB
D000287:Administration, Topical; D000473:Alkanes / Q000737:chemistry*; D000818:Animals; D002021:Buffers; D002463:Cell Membrane Permeability; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008744:Methylamines / Q000737:chemistry*; D051379:Mice; D008812:Mice, Hairless; D008954:Models, Biological; D009226:Myristates / Q000737:chemistry; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011237:Predictive Value of Tests; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
D000473:Alkanes; D002021:Buffers; D008744:Methylamines; D009226:Myristates; D010726:Phosphodiesterase Inhibitors; D011355:Prodrugs; D012997:Solvents; D014867:Water; C008205:isopropyl myristate; D013806:Theophylline