Qualitative structure-metabolism relationships in the hydrolysis of carbamates

被引：61

作者：

Vacondio, Federica ^{[1
]}

Silva, Claudia ^{[1
]}

Mor, Marco ^{[1
]}

Testa, Bernard ^{[2
]}

机构：

[1] Univ Parma, Dipartimento Farmaceut, I-43100 Parma, Italy

[2] Univ Hosp Ctr CHUV, Dept Pharm, Lausanne, Switzerland

来源：

DRUG METABOLISM REVIEWS | 2010年 / 42卷 / 04期

关键词：

Carbamates; structure-property relationships (SPR); hydrolysis; metabolic stability; drug metabolism; IN-VITRO METABOLISM; HIV-1 PROTEASE INHIBITOR; HUMAN-LIVER-MICROSOMES; C-14 N-ETHOXYCARBONYL-3-MORPHOLINOSYDNONIMINE MOLSIDOMINE; LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; REVERSE-TRANSCRIPTASE INHIBITOR; ORAL FLUOROPYRIMIDINE CARBAMATE; MECHANISM-BASED INACTIVATION; HUMAN MORICIZINE METABOLISM; NUCLEAR-MAGNETIC-RESONANCE;

D O I：

10.3109/03602531003745960

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 ((ROCONRR2)-O-3-R-1), 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 similar to Alkyl-OCO-N(Alkyl)(2) >= Alkyl-OCO-N(endocyclic) >= Aryl-OCO-N(Alkyl)(2) similar to Aryl-OCO-N(endocyclic) >= Alkyl-OCO-NHAryl similar to Alkyl-OCO-NHAcyl >> Alkyl-OCO-NH2 > Cyclic carbamates. This trend should prove useful in the design of carbamates as drugs or prodrugs.

引用

页码：551 / 589

页数：39

共 262 条

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