Govoni, M. and Bakker, R. A. and van de Wetering, I.. and Smit, M. J. and Menge, W. M. B. P. and Timmerman, H and Elz, Sigurd and Schunack, W. and Leurs, R. (2003) Synthesis and pharmacological identification of neutral histamine H-1-receptor antagonists. JOURNAL OF MEDICINAL CHEMISTRY, 46 (26). pp. 5812-5824. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
In the present study we searched for neutral antagonists for the human histamine H-1-receptor (H,R) by screening newly synthesized ligands that are structurally related to H1R agonists for their affinity using radioligand displacement studies and by assessing their functional activity via performing a NF-kappaB driven reporter-gene assay that allows for the detection of both agonistic and inverse agonistic responses. Starting from the endogenous agonist for the H1R, histamine, we synthesized and tested various analogues and ultimately identified several compounds with partial inverse agonistic properties and two neutral Hi-receptor antagonists, namely 2-[2-(4,4diphenylbutyl)-1H-imidazol-4-yl]ethylamine (histabudifen, 18d) (pK(i) = 5.8, alpha = 0.02) and 2-[2-(5,5-diphenylpentyl)-1H-imidazol-4-yl]ethylamine (histapendifen, 18e) (pK(i) = 5.9, alpha = -0.09).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONSTITUTIVELY ACTIVATING MUTATION; PROTEIN-COUPLED RECEPTORS; IN-VITRO PHARMACOLOGY; H-1 RECEPTOR; INVERSE AGONISM; MOLECULAR-CLONING; BINDING-SITE; INTRINSIC ACTIVITY; MESSENGER-RNA; UP-REGULATION; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Aug 2021 11:50 |
| Last Modified: | 10 Aug 2021 11:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38306 |
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