Qualitative structure-metabolism relationships in the hydrolysis of carbamates.
The aims of this review were 1) to compile a large number of reliable literature data on the metabolic hydrolysis of medicinal carbamates and 2) to extract from such data a qualitative relation between molecular structure and lability to metabolic hydrolysis. The compounds were classified according to the nature of their substituents (R³OCONR¹R²), and a metabolic lability score was calculated for each class. A trend emerged, such that the metabolic lability of carbamates decreased (i.e., their metabolic stability increased), in the following series: Aryl-OCO-NHAlkyl >> Alkyl-OCO-NHAlkyl ~ Alkyl-OCO-N(Alkyl)₂ ≥ Alkyl-OCO-N(endocyclic) ≥ Aryl-OCO-N(Alkyl)₂ ~ Aryl-OCO-N(endocyclic) ≥ Alkyl-OCO-NHAryl ~ Alkyl-OCO-NHAcyl >> Alkyl-OCO-NH₂ > Cyclic carbamates. This trend should prove useful in the design of carbamates as drugs or prodrugs.
Vacondio
Federica
F
Dipartimento Farmaceutico, Università degli Studi di Parma, Parma, Italy. federica.vacondio@unipr.it
Silva
Claudia
C
Mor
Marco
M
Testa
Bernard
B
D000818:Animals; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D002219:Carbamates; D004364:Pharmaceutical Preparations; D011355:Prodrugs