Substituted (Pyrroloamino)pyridines:  Potential Agents for the Treatment of Alzheimer's Disease

Abstract

A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure-activity relationships for this series is presented, along with the biological profiles of selected compounds.

Transient Amino‐Hydrazino‐Carbenes: A Radical Pathway for Intramolecular 1,2‐Migration Reactions

“…Dry, oxygen-free solvents were employed. 1 [24] NЈ-isopropyl-N,N-diphenylhydrazine, [25] N-phenylpyrazolidine, [26] chloro-N,N-diisopropylformamidinium chloride [27] were prepared according to literature procedures.…”

2,6-Dichloro-3-nitropyridine

“…For the role of the nitropyridine nucleus in the development of medicinal agents and in the field of agrochemicals, see: Davis et al (1996). For the properties and use of pyridine derivatives, see: Vacher et al (1998); Olah et al (1980); Bare et al (1989).…”

“…Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009). (Davis et al, 1996). It is seen from the current literature that pyridine derivatives have been developed and used as insecticidal agents (Vacher et al, 1998).…”

Functionalization of pyridines. 3. Reactions forming a carbon-heteroatom bond with group IV, V, and VI elements

“…An example of the substitution by hydrazine of a halogen atom in the 2-position that is not activated by any additional substituents has been reported [ 121 ]. The reaction of 4-chloropyridine hydrochloride with N-aminopyrrole in N-methylpyrrolidone gives a low yield of 4-(pyrrolylamino)pyridine, one member of a class of potential drugs for curing Alzheimer's disease [122].…”