Discovery of an Orally Active and Long-Acting DPP-IV Inhibitor through Property-Based Optimization with an in Silico Biotransformation Prediction Tool.
ChemMedChem
; 15(16): 1608-1617, 2020 08 19.
Article
en En
| MEDLINE
| ID: mdl-32558296
ABSTRACT
Long-acting dipeptidyl peptidase IV inhibitors have emerged as promising molecules for interventions for type 2 diabetes. Once weekly dosing brings greater patient compliance and more stable glycemic control. Starting from our previous highly potent compound with a thienoprimidine scaffold, which is unfortunately severely hit by hepatic biotransformation, a lead compound was rapidly generated by drawing on the experience of our previously discovered long-acting compounds with pyrrolopyrimidine scaffold. With the aid of an in silico biotransformation prediction tool, (R)-2-((2-(3-aminopiperidin-1-yl)-4-oxo-6-(pyridin-3-yl)thieno[3,2-d]pyrimidin-3(4H)-yl)methyl)-4-fluorobenzonitrile was eventually generated and determined to have high potency, a fine pharmacokinetic profile, and a long-acting inâ
vivo efficacy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Pirroles
/
Dipeptidil Peptidasa 4
/
Diabetes Mellitus Tipo 2
/
Inhibidores de la Dipeptidil-Peptidasa IV
/
Descubrimiento de Drogas
/
Hipoglucemiantes
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2020
Tipo del documento:
Article