Pyrazine CH- and NH-acids. Antithrombotic activity and chromatographic behaviour.
1. A series of newly synthesized pyrazine CH- and NH-acids was subjected to analytical and pharmacological studies. 2. The compounds were chromatographed in HPLC systems employing three reversed-phase columns and methanol-buffer solvents of various composition at acidic, neutral and alkaline pH. 3. Chemometrical analysis by the principal component method allowed for ordering of the compounds on a plane determined by the first two principal component axes. 4. Pharmacological tests were done for representatives of the series of compounds. 5. An in vivo antithrombotic assay on mice proved diversified bioactivity within the group of agents. 6. Attempts were undertaken to relate chromatographic behaviour to antithrombotic activity. 7. Based on the results obtained, an approach was proposed to reduce the number of pharmacological tests in selecting the most promising agents.
Petrusewicz
J
J
Department of Biopharmaceutics and Pharmacodynamics, Medical Academy of Gdansk, Poland.
Gami-Yilinkou
R
R
Kaliszan
R
R
Pilarski
B
B
Foks
H
H
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000577:Amides / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D009570:Nitriles / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D011719:Pyrazines / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D012044:Regression Analysis
D000577:Amides; D005343:Fibrinolytic Agents; D009570:Nitriles; D011719:Pyrazines; D000244:Adenosine Diphosphate; D003094:Collagen