Synthesis and transdermal permeation-enhancing activity of ketone, amide, and alkane analogs of Transkarbam 12.
Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium-5-(dodecyloxycarbonyl)pentylcarbamate, T12) is a highly active transdermal permeation enhancer. In this study, ketone, amide, and alkane analogs of T12 have been synthesized and evaluated for their permeation-enhancing activity using porcine skin and theophylline as a model drug. Replacement of ester by methylene and ketone, respectively, led to a significant decrease of activity. Amide analogs displayed lower activity in 60% propylene glycol and were comparable to T12 in isopropyl myristate. An intramolecular H-bond between ester and ammonium-carbamate group was suggested to be important for the permeation-enhancing activity of T12.
Holas
Tomás
T
Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
Vávrová
Katerina
K
Klimentová
Jana
J
Hrabálek
Alexandr
A
D000277:Adjuvants, Pharmaceutic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000473:Alkanes / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D012869:Skin Absorption / Q000187:drug effects; D013329:Structure-Activity Relationship; D013552:Swine; D013806:Theophylline / Q000494:pharmacology
D000277:Adjuvants, Pharmaceutic; D000473:Alkanes; D000577:Amides; D002219:Carbamates; D007659:Ketones; C492029:transkarbam 12; D013806:Theophylline