کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1375666 | 981942 | 2009 | 4 صفحه PDF | دانلود رایگان |

Lead optimisation starting from the previously reported selective quinoline NK3 receptor antagonists talnetant 2 (SB-223412) and 3 (SB-222200) led to the identification of 3-aminoquinoline NK3 antagonist 10 (GSK172981) with excellent CNS penetration. Investigation of a structurally related series of sulfonamides with reduced lipophilicity led to the discovery of 20 (GSK256471). Both 10 and 20 are high affinity, potent NK3 receptor antagonists which despite having different degrees of CNS penetration produced excellent NK3 receptor occupancy in an ex vivo binding study in gerbil cortex.
SAR investigation in the quinoline series of NK3 antagonists led to identification of 3-amino quinoline 10 (GSK172981) and sulfonamide 20 (GSK256471). Both compounds are high affinity, potent NK3 receptor antagonists which produce excellent NK3 receptor occupancy in an ex vivo binding study in gerbil cortex.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 3, 1 February 2009, Pages 837–840