| Autor: |
Smith PW; Medicinal Chemistry, Neuroscience CEDD GlaxoSmithKline Research & Development, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. Paul.W.Smith@GSK.com, Wyman PA, Lovell P, Goodacre C, Serafinowska HT, Vong A, Harrington F, Flynn S, Bradley DM, Porter R, Coggon S, Murkitt G, Searle K, Thomas DR, Watson JM, Martin W, Wu Z, Dawson LA |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Feb 01; Vol. 19 (3), pp. 837-40. Date of Electronic Publication: 2008 Dec 07. |
| DOI: |
10.1016/j.bmcl.2008.12.005 |
| Abstrakt: |
Lead optimisation starting from the previously reported selective quinoline NK(3) receptor antagonists talnetant 2 (SB-223412) and 3 (SB-222200) led to the identification of 3-aminoquinoline NK(3) 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 NK(3) receptor antagonists which despite having different degrees of CNS penetration produced excellent NK(3) receptor occupancy in an ex vivo binding study in gerbil cortex. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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