Rapid hydrolysis of amides under physiological conditions: Influence of the microenvironment on the stability of the amide bond

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 3, 1998, Pages 285-288

  Glusenkamp, K H ^a   Mengede, C ^a   Drosdziok, W ^a   Jahde E ^a   Rajewsky, M F ^a  

^a UNIVERSITY OF ESSEN MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE;

ARTICLE; CHEMICAL BOND; DRUG HYDROLYSIS; DRUG STABILITY; KINETICS; PROTON TRANSPORT;

AMIDES; HALF-LIFE; HYDROLYSIS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032477769     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00007-9     Document Type: Article

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12. 3 synthesized a maleic acid amide which showed a half-life of about 16 h at pH 6.6, but at pH 1 the lability of this carboxyamide increased to a half-life of a few seconds. Because of the architecture, the bicyclic carboxyamide 9a combines the unusual kinetic properties of the aforementioned different ß-carboxyamides and maleic amide derivatives. In contrast to the saturated compound 9a the corresponding unsaturated compound revealed a very stable amide bond. We assume that the amide formation was accompanied by an intramolecular lactonization step. In this case the kinetically active carboxy group is protected. This compounds appear to be good candidates for liberation of the active caboxy group by an enzymatic reaction. Glüsenkamp, K.-H. and Rajewsky, M.F. unpublished results.
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