Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1988-10-27
1990-11-27
Springer, David B.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D20508
Patent
active
049737082
ABSTRACT:
The novel compound, 3-hydroxy-N-methylpyrrolidone, is effective as a transdermal enhancer for the absorption of drugs through the skin of humans and animals. The 3-hydroxy-N-methylpyrrolidone is prepared from delta-butyrolactone which is converted to methyl 2,4-dibromobutyrate, this intermediate is reacted with methylamine to form N-methyl-2,4-dibromobutyramide, this intermediate is converted to 3-bromo-N-methyl-2-pyrrolidone by ring closure, and the 3-bromo-N-methyl-2-pyrrolidone is reacted with an alkaline earth metal carbonate or alkaline metal carbonate to form 3-hydroxy-N-methyl-2-pyrrolidone.
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GAF Corp.: "M-Pyrol (N-methyl-2-pyrrolidone) Handbook," GAF Corp., New York, 1972.
Wells, D. A. et al: Disposition and Metabolism of Double-Labeled [.sup.3 H and .sup.14 C] N-methyl-2-pyrrolidone in the Rat. Drug Met. Disps., 16, 243-249 (1988).
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Akhter et al, Absorption through Human Skin of Ibuprofen and Flurbiprofen; Effect of Dose Variation, Deposited Drug Films, Occlusion and the Penetration Enhancer N-methyl-2-Pyrrolidone, J. Pharm. Pharmacol., 37, 27-37 (1985).
Monkhouse et al, Transdermal Drug Delivery--Problems and Promises, Drug Development and Industrial Pharmacy, 14 (2 and 3), 183-209 (1988).
Digenis George A.
Doll Walter J.
Hawi Amale
Springer David B.
University of Kentucky Research Foundation
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