Synthesis and selective vasodilating properties of esters of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydro-pyridine-3,5-di- carboxylic acid.
This study presents the synthesis of new 1,4-dihydropyridine (DHP) derivatives which are phenoxy- and alkoxyalkyl esters of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine-3,5-dica rbo xylic acid and reports on the biological activity of the compounds. It was found that the DHP derivatives showed high affinity to the DHP receptor of rat brain membranes and antagonize potently the potassium depolarization-induced vasospasm in a fashion compatible with the assumption of a calcium entry blockade. The higher vasodilating potency of especially compound III for the cerebral vasculature might represent an improved selectivity profile due to specific substitution patterns of the DHP molecule by increasing lipophilicity. Thus, the new DHP derivatives might be useful as therapeutic agents for hypertension and impaired cerebral microcirculation.
Dubur
G J
GJ
Institute for Organic Synthesis, Riga (USSR), Fed. Rep. of Germany.
Veveris
M M
MM
Weinheimer
G
G
Bisenieks
E A
EA
Makarova
N R
NR
Kimenis
A A
AA
Uldrikis
J R
JR
Lukevics
E J
EJ
Dooley
D
D
Osswald
H
H
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017275:Isradipine; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000138:chemical synthesis*
D004095:Dihydropyridines; D004952:Esters; D011725:Pyridines; D014665:Vasodilator Agents; D011188:Potassium; D002118:Calcium; D017275:Isradipine