[3H]UR‐DE257: Development of a Tritium‐Labeled Squaramide‐Type Selective Histamine H2 Receptor Antagonist. Issue 1 (15th October 2014)

• Record Type: Journal Article
• Authors: Baumeister, Paul; Erdmann, Daniela; Biselli, Sabrina; Kagermeier, Nicole; Elz, Sigurd; Bernhardt, Günther; Buschauer, Armin
• Is Part Of: ChemMedChem. Volume 10:Issue 1(2015:Jan.)
• Page Start: 83
• Page End: 93
• Publication Date: 2014-10-15
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402344
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A series of new piperidinomethylphenoxypropylamine‐type histamine H₂ 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 <italic>N</italic>‐[6‐(3, 4‐dioxo‐2‐{3‐[3‐(piperidin‐1‐ylmethyl)phenoxy]propylamino}cyclobut‐1‐enylamino)hexyl]‐(2, 3‐³H₂)propionic amide ([³H]UR‐DE257) was performed. The radioligand (specific activity: 63 Ci mmol⁻¹) had high affinity for human, rat, and guinea pig H₂R (hH₂R, Sf9 cells: <italic>K</italic>_d, saturation binding: 31 n<sc>M</sc>, kinetic studies: 20 n<sc>M</sc>). UR‐DE257 revealed high H₂R selectivity on membranes of Sf9 cells, expressing the respective hH_{<italic>x</italic>}R subtype (<italic>K</italic>_i values: hH₁R: &gt;10 000 n<sc>M</sc>, hH₂R: 28 n<sc>M</sc>, hH₃R: 3800 n<sc>M</sc>, hH₄R: &gt;10 000 n<sc>M</sc>). In spite of insurmountable antagonism, probably due to rebinding of [³H]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.</p> </abstract>