Soliman, Beatrice and Wang, Ning and Zagotto, Giuseppe and Pockes, Steffen (2019) Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors. ARCHIV DER PHARMAZIE, 352 (9): e1900107. ISSN 0365-6233, 1521-4184
Full text not available from this repository. (Request a copy)Abstract
Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR-PI376, as highly potent agonists at the human histamine H-4 receptor (hH(4)R). While imidazole-containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six-membered heterocycles (piperidine, morpholine, thiomorpholine, and N-methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C-3-C-5) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand-binding assays exhibited only very weak activity at the hH(1)R and hH(3)R, while nearly all compounds were inactive at the hH(2)R and hH(4)R. In the case of piperidine-containing compounds, moderate affinities at the hH(3)R over the single-digit micromolar range were detected.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | H-4 RECEPTOR; HIGHLY POTENT; SELECTIVITY; ANTAGONISTS; LIGANDS; AGONIST; PHARMACOLOGY; CHEMOTHERAPY; IMPROMIDINE; SUBTYPES; aliphatic heterocycles; bioisosteres; cyanoguanidines; histamine receptors; UR-PI376 |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Apr 2020 09:08 |
| Last Modified: | 02 Apr 2020 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26593 |
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