Synthesis of carboxy-nifedipine and its use in the preparation of an affinity resin for the 1,4-dihydropyridine receptor.
Affinity chromatography represents a potentially valuable approach to study the calcium antagonist receptor in many tissues. Methods have been developed to synthesize carboxy-analogues of the 1,4-dihydropyridine calcium antagonists. Carboxy-nifedipine ([+/-]1,4-dihydro-2,6 dimethyl-4-[3-nitrophenyl] pyridine-3-carboxylic acid-5-carboxylic methyl ester) was prepared with a yield of 50% and its structure has been thoroughly characterized. Carboxy-nifedipine has been coupled to a hexamine-agarose resin through an acid chloride intermediate producing an affinity resin (1.6 mumol of drug/ml). Experiments have shown that this affinity resin is capable of binding the [3H]nitrendipine receptor solubilized from transverse tubule membranes.
D000818:Animals; D015220:Calcium Channels; D002846:Chromatography, Affinity / Q000379:methods; D005260:Female; D008566:Membranes / Q000378:metabolism; D009124:Muscle Proteins / Q000302:isolation & purification; D009132:Muscles / Q000032:analysis / Q000648:ultrastructure; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000302:isolation & purification*
D015220:Calcium Channels; D009124:Muscle Proteins; D011978:Receptors, Nicotinic; C047931:1,4-dihydro-2,6-dimethyl-4--(3-nitrophenyl)pyridine-3-carboxylic acid-5-carboxylic methyl ester; D009543:Nifedipine