Synthesis and Structure-Activity Relationships of Some Aminopyridines, Imidazopyridines, and Triazolopyridines

Abstract

Devised Manuscript Deceived January It), />'/.! 2-and 4-w-substituted alkylamiiio-3-aminupyridines and the corresponding ñ-nitro, bromo, amino, alkoxycarbonyl, and carboxamide derivatives and 3-substituted amino-4-aminopyridines have been synthesized and cyclized to the corresponding imidazoand triazolo[4,5-6]-and -[4,5-c]pyridines. These compounds showdiverse types of pharmacological activity. Their structure-activity relationship has been discussed.Certain aminoand diaminopyridines prepared as intermediates in the synthesis of potential purine an-tagonists2 were found to possess analeptic and pressor activities which were particularly marked in 2,3-and 3.4-diaminopyridines.3 A survey of the literature4 showed that a number of 2,3-and 3,4-diaminopyridines with substituents in the ring and also on the amino groups have been reported and cyclized to the corre-70, 591 (1951).

3,4-Diaminopyridine safety in clinical practice: an observational, retrospective cohort study

“…Toxicological, pharmacological and long-term safety data on the clinical use of 3,4-DAP are still insufficient [21,33,38,39]. Despite its widespread use, the efficacy and safety of 3,4-DAP as symptomatic therapy for fatigue in MS patients have not yet been evaluated with welldesigned prospective studies [35].…”

2‐Aminopyridin [MAK Value Documentation in German language, 2000]

“…Bei Mäusen wurde eine orale LD 50 von 50 mg/kg KG (Trochimowicz et al 1994), eine intraperitoneale von 35 mg/kg KG (Vohra et al 1965) und eine intravenöse von 23 mg/kg KG (Trochimowicz et al 1994) angegeben. Die dermale LD 50 betrug bei Meerschweinchen 500 mg/kg KG (Trochimowicz et al 1994 …”

4‐Aminopyridine: Use in Multiple Sclerosis

“…4-Aminopyridine crosses the blood-brain barrier readily and has three clearly demonstrated effects on the central nervous system: analeptic activity, stimulation of respiration, and convulsant activity. 4-Aminopyridine has been demonstrated to arouse dogs under morphine narcosis (83), antagonize barbiturate-induced coma in mice (103), and reduce recovery time in monkeys (53) and humans (2) treated with ketamine-diazepam anesthesia. The mechanism of analeptic activity has not been examined in detail, but increases in central release of acetylcholine were proposed (2,7 1).…”