4-Alkyl-1,4-dihydropyridine derivatives as specific PAF-acether antagonists

Abstract

A new series of 4-alkyl-1,4-dihydropyridines (1,4-DHP) were synthesized and evaluated for their ability to inhibit washed rabbit platelet aggregation induced by PAF-acether (1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) and to reverse PAF-induced hypotension in anesthetized rats. Additionally, compounds were evaluated for their ability to inhibit the binding of radiolabeled PAF to its receptor on rabbit platelets. Among these compounds, 6I and 6L were the most potent and specific antagonists. At concentrations up to 100 microM, neither compound 6I nor compound 6L caused platelet aggregation nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Compound 6L did not show in vitro calcium channel blocker activity measured on vascular smooth muscle preparations of rabbit aorta and on [3H]nitrendipine binding assays. The compound did not show any cardiovascular effects in anesthetized rat at iv doses up to 1000 micrograms/kg, and the Ki value was 568.62 nmol. These results indicate that compound 6L is a potent and specific PAF antagonist with 1,4-dihydropyridine structure but devoid of a significant cardiovascular activity related to calcium-antagonist properties.

Solvent‐free neat synthetic route to tetrahydroacridinones

“…The chemical modifications carried out on the DHP ring [7] such as the presence of different substituents [8] or heteroatoms [9] have allowed expansion of the structure activity relationship and afforded some insights into the molecular interactions at the receptor level. 1,4-DHPs are well known because of their pharmacological profiles [10,11]. Furthermore, hexahydroquinolines play an important role in medicinal chemistry as anxiolytic [12] and memory enhancers [13] and show marked positive inotropic effect [14].…”

Zn[(L)-proline] as a Recyclable and Green Catalyst for Efficient and One-pot Three-Component Synthesis of 1,4-Dihydro- pyridines Under Solvent-Free and Microwave Irradiation Conditions

“…a wide rang of pharmacological and biological activities such as anti-hypertensive, anti-anginal [4][5][6] ,antitumor 7 , anti-inflammatory activity [8][9] , antitubercular activity 10 , analgesic activity 11 , antithrombotic 12,13 . Other activities like anti-convulsant 14 , stress protective effect 15 , cardio depressant activity 16 .…”

Catalyst free, one-pot, facile synthesis of novel pyrazolo-1,4-dihydropyridine derivative form pyranopyrazoles

“…1,4-DHPs are an important class of Ca 2+ channel blockers and are also known to be effective cardiovascular agents for the treatment of hypertension. Apart from these activities, DHPs are found to be as platelet-activity factor antagonists [8], calcium antagonists [9], antihypertensives [10], cerebral antischemic activity in the treatment of Alzheimer's disease and chemosensitizer acting in tumor therapy. Although the synthesis of pyrazolo-1,4-dihydropyridines using expensive starting material like 3-methyl-4,5-dihydro-1H-pyrazol-5-amine or 3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-amine, has considerably contributed to the development of new pyrazolo-1,4-DHPs [11][12][13][14][15], yet, the achieved molecule remains beyond the reach of most manufacturers, as it involves the usage of expensive starting material.…”