Kinetic and mechanistic insight into the thermodynamic degradation of saxagliptin.
J Org Chem
; 76(24): 10332-7, 2011 Dec 16.
Article
em En
| MEDLINE
| ID: mdl-22054301
ABSTRACT
The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of this key byproduct. Important findings of this work are the identification of a profound solvent effect and the determination of an autocatalytic pathway. Both of these phenomena result from transition structures involving proton transfer.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Prótons
/
Adamantano
/
Dipeptídeos
/
Dicetopiperazinas
/
Inibidores da Dipeptidil Peptidase IV
/
Amidinas
/
Hipoglicemiantes
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos