Radiosynthesis of [¹¹C]nifedipine and [¹¹C]nicardipine

Abstract

The radiosyntheses of the dihydropyridine (DHP) calcium channel blockers [IlCInifedipine and [I 1Clnicardipine by alkylation of the appropriate DHP 3-monocarboxylic acid anion with [ 11CIiodomethane are described. Isolated radiochemical yields of 30-50% were obtained 25 minutes after the end-of-bombardment, with specific activities of 400-1400 mCi/pmol at the end-of-synthesis. A variety of positron emitting DHPs with different ester side chains in the 3 and 5 positions on the DHP ring may be prepared by this approach using currently available labelled alkylating agents.

Radiosynthesis of dimethyl-2-[18F]-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate for L-type calcium channel imaging

“…the method remains useful for incorporation of 11 C-CH 3 as an ester group [8]. In another study a carbon-11 labeled DHP, [ 11 C]S12968, was used to measure the myocardial dihydropyridine binding site density using positron emission tomography [9][10][11].…”

Synthesis of carbon‐11 labelled calcium channel antagonists

“…Dihydropyridine monocarboxylic acids 12-15 were converted in-situ into their corresponding potassium salts 1611-19a followed by methylation with 11CH31 under phase transfer conditions to yield the products [16][17][18][19] in high purity and good chemical and radiochemical yields, scheme 4…”

The Hantzsch reaction for nitrogen-13 PET: preparation of [13N]nifedipine and derivatives

“…6,7 The Hantzsch dihydropyridine (DHP) synthesis is a multicomponent reaction between an aldehyde, two equivalents of a b-keto ester, and an amine (or ammonia). Clinically, 1,4-dihydropyridines including dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (nifedipine), are used as anti-hypertensive and anti-anginal drugs in cardiovascular disease by acting at voltage-gated calcium channels in peripheral blood vessels and the heart; 8,9 these have been radiolabelled using a range of radionuclides including 3 H, 14 C, 11 C, 125 I, and 18 F in order to probe modes of action, pharmacokinetics and metabolism of this class of compounds, and to study the pathophysiology of calcium channels in cardiovascular diseases. [10][11][12][13][14][15][16][17][18][19][20][21] To expand the arsenal of 13 N-radiolabelling tools, we explored the Hantzsch dihydropyridine synthesis as a strategy to access [ 13 N]1,4dihydropyridines ([ 13 N]1,4-DHPs) using aqueous [ 13 N]ammonia as a synthetic precursor (Fig.…”