| Autor: |
Lim HD; Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands., Istyastono EP, van de Stolpe A, Romeo G, Gobbi S, Schepers M, Lahaye R, Menge WM, Zuiderveld OP, Jongejan A, Smits RA, Bakker RA, Haaksma EE, Leurs R, de Esch IJ |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2009 Jun 01; Vol. 17 (11), pp. 3987-94. Date of Electronic Publication: 2009 Apr 11. |
| DOI: |
10.1016/j.bmc.2009.04.007 |
| Abstrakt: |
Previous studies have demonstrated that clobenpropit (N-(4-chlorobenzyl)-S-[3-(4(5)-imidazolyl)propyl]isothiourea) binds to both the human histamine H(3) receptor (H(3)R) and H(4) receptor (H(4)R). In this paper, we describe the synthesis and pharmacological characterization of a series of clobenpropit analogs, which vary in the functional group adjacent to the isothiourea moiety in order to study structural requirements for H(3)R and H(4)R ligands. The compounds show moderate to high affinity for both the human H(3)R and H(4)R. Furthermore, the changes in the functional group attached to the isothiourea moiety modulate the intrinsic activity of the ligands at the H(4)R, ranging from neutral antagonism to full agonism. QSAR models have been generated in order to explain the H(3)R and H(4)R affinities. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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