851526-82-4

Upstream product

• 848591-68-4 tert-butyl 3-benzyl-3,6-diazabicyclo[3.2.1]octane-6-carboxylate 
• 407-25-0 trifluoroacetic anhydride 
• 100-46-9 benzylamine 
• 188345-71-3 2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]hept-5-ene 

Downstream Products

• 851526-81-3 tert-butyl 3,6-diazabicyclo[3.2.1]octane-3-carboxylate 

Relevant academic research and scientific papers

Structure-activity studies and analgesic efficacy of N-(3-pyridinyl)- bridged bicyclic diamines, exceptionally potent agonists at nicotinic acetylcholine receptors

A series of exceptionally potent agonists at neuronal nicotinic acetylcholine receptors (nAChRs) has been investigated. Several N-(3-pyridinyl) derivatives of bridged bicyclic diamines exhibit double-digit-picomolar binding affinities for the α4β2 subtype, placing them with epibatidine among the most potent nAChR ligands described to date. Structure-activity studies have revealed that substitutions, particularly hydrophilic groups in the pyridine 5-position, differentially modulate the agonist activity at ganglionic vs central nAChR subtypes, so that improved subtype selectivity can be demonstrated in vitro. Analgesic efficacy has been achieved across a broad range of pain states, including rodent models of acute thermal nociception, persistent pain, and neuropathic allodynia. Unfortunately, the hydrophilic pyridine substituents that were shown to enhance agonist selectivity for central nAChRs in vitro tend to limit CNS penetration in vivo, so that analgesic efficacy with an improved therapeutic window was not realized with those compounds.

Substituted diazabicycloalkane derivatives

Compounds of formula (I) [in-line-formulae]Z-Ar1—Ar2??(I) [/in-line-formulae] wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.