122956-69-8

Upstream product

• 63604-59-1 2-methyl-1H-imidazo[4,5-c]pyridine 
• 873-74-5 4-Aminobenzonitrile 
• 89-98-5 2-chloro-benzaldehyde 
• 110262-80-1 (E)-3-Amino-but-2-enoic acid tert-butylamide 
• 122957-08-8 ethyl 4'-(2-methylimidazo[4,5-c]pyridin-1-yl)benzoylacetate 
• 122957-33-9 4-[N-(4-cyanophenyl)amino]-3-nitropyridine 
• 122957-32-8 4-(2-methylimidazo[4,5-c]pyrid-1-yl)benzonitrile 
• 122957-34-0 3-amino-4-[N-(4-cyanophenyl)amino]pyridine 
• 142161-57-7 2-methylimidazo<4,5-c>pyridine 5-oxide 
• 13091-23-1 4-chloro-3-nitropyridine 
• 54-96-6 3,4-diaminopyridine 

Relevant academic research and scientific papers

1,4-Dihydropyridines as Antagonists of Platelet Activating Factor. 1. Synthesis and Structure-Activity Relationships of 2-(4-Heterocyclyl)phenyl Derivatives

A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or 3-aminocrotonate esters.Structure-activity relationships were evaluated where PAF antagonist activity was measured in vitro by determining the concentration of compound (IC50) required to inhibit the PAF-induced aggregation of rabbit washed platelets,and in vivo by determining the oral dose (ED50) which protected mice from a lethal injection of PAF.The nature of the substituent at the dihydropyridine 2-position was found to be important for both in vitro and in vivo activity, whereas there was greater flexibility for structural variation at the 4- and 5-positions.The most potent compound was 4-(2-chlorophenyl)-1,4-dihydro-3-(ethoxycarbonyl)-6-methyl-2-pyrid-1-yl)phenyl>-5-pyridine (17, UK-74,505), IC50 = 4.3 nM, ED50 = 0.26 mg/kg po, which was found to be approximately 33 times more potent in vitro (rabbit platelet aggregation) and about 8 times more potent in vivo (murine lethality) than WEB2086.Compound 17 also exhibited a long duration of action in the dog (inhibition of PAF-induced whole blood aggregation ex vivo was maintained for > 24 h following a single oral dose of 75 μg/kg) and was highly selective as a PAF antagonist, showing only weak affinity (IC50 = 6600 nM) for the nitrendipine binding site.As a result of its high oral potency, selectivity, and duration of action, UK-74,505 has been selected for clinical evaluation.