AI Article Synopsis
- A series of modified dihydropyridines were studied for their effectiveness as calcium antagonists, highlighting their unique basic side chains.
- Amlodipine (compound 17) was noted for its similar potency to nifedipine, with a long elimination half-life of 30 hours in dogs and nearly complete oral bioavailability.
- Research revealed that most of the drug's activity was linked to its (-) enantiomer, and X-ray studies suggested a weak hydrogen bond that may influence its stability or function.
Article Abstract
A series of dihydropyridines substituted at the 2-position by basic side chains are described and their potencies as calcium antagonists listed. One compound, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5- methoxycarbonyl-6-methyl-1,4-dihydropyridine (17, amlodipine) was found to be comparable in potency to nifedipine and to have an elimination half-life of 30 h in dogs. Oral bioavailability approached 100%, and hemodynamic responses were gradual in onset and long-lasting in effect. The two enantiomers have been prepared, and the bulk of the activity was found to reside with the (-) isomer, 18. X-ray crystallographic studies, carried out on a close analogue of 17, suggest the existence of a weak hydrogen bond between the side-chain oxygen and the proton on the ring nitrogen.
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| http://dx.doi.org/10.1021/jm00159a022 | DOI Listing |
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