Structure-activity relationships of strychnine analogues at glycine receptors

TY - JOUR

T1 - Structure-activity relationships of strychnine analogues at glycine receptors

AU - Mohsen, A.M.Y.

AU - Heller, Eberhard

AU - Holzgrabe, Ulrike

AU - Jensen, Anders A.

AU - Zlotos, Darius P.

PY - 2014/8

Y1 - 2014/8

N2 - Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC 50 value of 1.6μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21) C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors

AB - Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC 50 value of 1.6μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21) C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors

U2 - 10.1002/cbdv.201400110

DO - 10.1002/cbdv.201400110

M3 - Journal article

C2 - 25146769

SN - 1612-1872

VL - 11

SP - 1256

EP - 1262

JO - Chemistry and Biodiversity

JF - Chemistry and Biodiversity

IS - 8

ER -