TY - JOUR
T1 - Synthesis, screening and docking of small heterocycles as Glycogen Phosphorylase inhibitors
AU - Schweiker, Stephanie S.
AU - Loughlin, Wendy A.
AU - Lohning, Anna S.
AU - Petersson, Maria J.
AU - Jenkins, Ian D.
PY - 2014/9/12
Y1 - 2014/9/12
N2 - A series of morpholine substituted amino acids (phenylalanine, leucine, lysine and glutamic acid) was synthesized. A fragment-based screening approach was then used to evaluate a series of small heterocycles, including morpholine, oxazoline, dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3-pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H- benzimidazole, as potential inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved potency (IC50 of 25 μM) and had good LE and LELP values, as compared to heterocycles 1, 5, 9-13 and 19 (IC50 values of 1.1 mM-23.9 mM). A docking study using the crystal structure of human liver Glycogen Phosphorylase, provided insight into the interactions of heterocycles 5, 7, 9-13 and 19 with Glycogen Phosphorylase.
AB - A series of morpholine substituted amino acids (phenylalanine, leucine, lysine and glutamic acid) was synthesized. A fragment-based screening approach was then used to evaluate a series of small heterocycles, including morpholine, oxazoline, dihydro-1,3-oxazine, tetrahydro-1,3-oxazepine, thiazoline, tetrahydro-1,3-pyrimidine, tetrahydro-1,3-diazepine and hexahydro-1H- benzimidazole, as potential inhibitors of Glycogen Phosphorylase a. Thiazoline 7 displayed an improved potency (IC50 of 25 μM) and had good LE and LELP values, as compared to heterocycles 1, 5, 9-13 and 19 (IC50 values of 1.1 mM-23.9 mM). A docking study using the crystal structure of human liver Glycogen Phosphorylase, provided insight into the interactions of heterocycles 5, 7, 9-13 and 19 with Glycogen Phosphorylase.
UR - http://www.scopus.com/inward/record.url?scp=84905181692&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2014.07.063
DO - 10.1016/j.ejmech.2014.07.063
M3 - Article
C2 - 25062009
AN - SCOPUS:84905181692
SN - 0223-5234
VL - 84
SP - 584
EP - 594
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -