Baumeister, Paul and Erdmann, Daniela and Biselli, Sabrina and Kagermeier, Nicole and Elz, Sigurd and Bernhardt, Guenther and Buschauer, Armin (2015) [H-3]UR-DE257: Development of a Tritium-Labeled Squaramide-Type Selective Histamine H-2 Receptor Antagonist. CHEMMEDCHEM, 10 (1). pp. 83-93. ISSN 1860-7179, 1860-7187
Full text not available from this repository. (Request a copy)Abstract
A series of new piperidinomethylphenoxypropylamine-type histamine H-2 receptor (H2R) antagonists with different substituted urea equivalents was synthesized and characterized in functional in vitro assays. Based on these data as selection criteria, radiosynthesis of N-[6-(3,4-dioxo-2-{3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino}cyclobut-1-enylamino)hexyl]-(2,3-H-3(2))propionic amide ([H-3]UR-DE257) was performed. The radioligand (specific activity: 63Cimmol(-1)) had high affinity for human, rat, and guinea pig H2R (hH(2)R, Sf9 cells: K-d, saturation binding: 31nM, kinetic studies: 20nM). UR-DE257 revealed high H2R selectivity on membranes of Sf9 cells, expressing the respective hH(x)R subtype (K-i values: hH(1)R: >10000nM, hH(2)R: 28nM, hH(3)R: 3800nM, hH(4)R: >10000nM). In spite of insurmountable antagonism, probably due to rebinding of [H-3]UR-DE257 to the H2R (extended residence time), the title compound proved to be a valuable pharmacological tool for the determination of H2R affinities in competition binding assays.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GUINEA-PIG; HIGHLY POTENT; HIGH-AFFINITY; PHARMACOLOGICAL CHARACTERIZATION; NONPEPTIDE ANTAGONISTS; BIOISOSTERIC APPROACH; RECEPTOR SUBTYPES; QUADRATIC ACID; RADIOLIGAND; AGONISTS; binding kinetics; histamine H-2 receptors; insurmountable antagonism; radiochemistry; rebinding |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Aug 2019 06:25 |
| Last Modified: | 05 Aug 2019 06:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6367 |
Actions (login required)
 |
View Item |
