Bridged 5,6,7,8‐Tetrahydro‐1,6‐naphthyridines, Analogues of Huperzine A: Synthesis, Modelling Studies and Evaluation as Inhibitors of Acetylcholinesterase

Abstract

Derivatives of 6,8‐bridged 5,6,7,8‐tetrahydro‐1,6‐naphthyridines, designed as analogues of huperzine A, were synthesised and evaluated as inhibitors of acetylcholinesterase. In a first approach, C3‐bridged naphthyridines were constructed by internal nucleophilic aromatic substitution of 2‐chloro‐3‐(1‐piperidinylmethyl)pyridine precursors containing a 3‐CO2Me group on the 1‐piperidinyl ring moiety. Alternatively, ring‐closing metathesis on 6,8‐diallyl‐substituted tetrahydro‐1,6‐naphthyridines was applied to construct an unsaturated C4 bridge. Some of the target compounds showed inhibition of acetylcholinesterase but lower than that of huperzine A. The relative order of inhibition activities could be rationalised by comparative docking simulation studies on the basis of the known crystal structure of the acetylcholinesterase–huperzine A complex.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Domino synthesis of functionalized 1,6-naphthyridines and their in vitro anti-inflammatory and anti-oxidant efficacies

“…2,3 These pyridine structures are the most significant because of their wide spectrum of promising biological activities such as anticonvulsants, 4 anti-inflammatory, 5 antimitotic, 6 agents antioxidant, 7,8 anticancer, 9,10 and antimicrobial activities. 11 Similarly, 1,6-naphthyridines [12][13][14][15][16][17] have established significant attention due to their broad range of bioactivities [18][19][20][21][22][23][24] such as antimicrobial, 25 anti-analgesic, 26 antifungal, 27,28 anticancer, [29][30][31] antioxidant, 31 anti-inflammatory, [27][28][29]32 antiarrhythmic, 33 antitumor 34 , anti HSV-1 35 anti-HIV 36,37 activities and act as inhibitors of acetylcholinesteras. 38 Structures of few previously reported biologically active 1,6-naphyridines (A-G) are shown in Figure 1.…”

Preparation of Pyridine N-oxide Derivatives in Microreactor

“…[19,20] The 2-hydroxypyridines can be further functionalized into different 2-substituted pyridine derivatives. [21][22][23][24][25][26] N-oxidants Different N-oxidants are well known in the literature for heteroatom oxidation. In our studies, the reactions were carried out with m-CPBA in DCM or with aqueous H 2 O 2 in acetic acid, so these compounds were described in detail regarding their safety aspect.…”

Synthesis and Antimicrobial Activities of Iminothioether Linkers on Cyclopenta[a]phenanthrene Derivatives

“…Benzo [1,6]naphthyridine derivatives are class of fused heterocyclic compounds that exhibit broad spectrum of biological activities such as antimalarial [1], inhibitor of HIV-1 integrase [2][3][4][5], HCMV [6,7], FGF receptor-1 tyrosine kinase [8] and the enzyme acetyl cholinesterase [9,10]. The SAR studies of these types of compounds were having quinoline nucleus as carrier of several cytotoxic agents [11,12].…”