Synthesis and evaluation of biological activity of two novel tritium‐labeled derivatives of riodipine

Abstract

2, 6‐Dimethyl‐3‐methoxycarbonyl‐5–([2, 3‐3H2] ‐n‐propoxy‐carbonyl)‐4‐(2′ ‐difluoromethoxyphenyl)‐1, 4‐dihydropyridine and 2, 6‐dimethyl‐3, 5‐di([2, 3‐3H2] ‐n‐propoxycarbonyl)‐4‐(2′‐difluoromethoxyphenyl)‐1, 4‐dihydropyridine were prepared by catalytic tritiation of the respective 3‐allyloxy‐carbonyl and 3,5‐di (allyloxycarbonyl) derivatives of riodipine. The two novel radioactively labeled 1,4‐dihydropy‐ridine derivatives obtained were shown to be suitable molecular tools for the identification of membrane‐bound and solubilized dihydropyridine receptors associated with calcium channels in rabbit skeletal muscle.

Cav1.2, Cell Proliferation, and New Target in Atherosclerosis

“…DHPs bind to Ca v 1.2 with high affinity in equimolar ratio and are excellent probes for the expression of total (functional and dormant) Ca v 1.2 in the plasma membrane. The test system was based on the measurement of specific binding of 2,6-dimethyl-3-methoxycarbonyl-5-([2,3- 3 H 2 ]-n-propoxycarbonyl)-4-(2′-difluoromethoxyphenyl)-1,4-dihydropyridine ([ 3 H]PMD, NCBI PubChem CID 14267917) [ 15 ] to human embryonic diploid fibroblasts grown in Eagle's medium supplemented with 10% serum. Under standard conditions of incubation (1 h at room temperature in Tris-buffered saline) [ 3 H]PMD interacted with K d ≈ 3.9 nM with a single class of DHP receptors that were present at the maximum density ( B max ) of ≈ 1.2 pmol/10 6 cells in a sparse culture of fibroblasts ( ≈ 3–5 × 1,000/cm 2 ) [ 16 ].…”