ChemInform Abstract: Synthesis, Pharmacological Activities and Physico‐Chemical Properties of 4‐(Substituted amino/N4‐arylpiperazinyl/aminocarbonyl)‐2,3‐polymethylenequinolines.

Abstract

212ChemInform Abstract A large number of title compounds as well as some N-substituted aminoacridines are synthesized according to known procedures in moderate to good yields and tested for their pharmacological activity. Among them, the compounds (I) (local anesthetics), (IIa) (antihistaminic activity) and (IIb) (analeptic activity) are found to be the most active ones. The results for all products are tabulated. Witha view to determining relationship between the physico-chemical properties and the biological activities, pKa, lipophilicity and DNA binding of some compounds of each type are studied.

Novel Tacrine Analogues for Potential Use against Alzheimer's Disease: Potent and Selective Acetylcholinesterase Inhibitors and 5-HT Uptake Inhibitors

“…Anthranilonitrile ( 8 ) (5.0 g, 42.3 mmol), cyclooctanone ( 9c ) (6.1 mL, 46.7 mmol), and boron trifluoride diethyl etherate (1 M, 5.6 mL, 46.7 mmol) gave the title compound ( 10c ) (7.4 g, 78% crude). Recrystallized: mp 198−200 °C (EtOH) (lit . mp 198−200 °C); 1 H NMR (CDCl 3 ) δ 1.20−1.55 (4H, m, 2C H 2 ), 1.60−1.95 (4H, m, 2C H 2 ), 2.87 (2H, m, C H 2 ), 3.10 (2H, m, C H 2 ), 4.70 (2H, br s, exchanges with D 2 O, N H 2 ), 7.39 (1H, td, J = 6.8, 1.3, aryl- H ), 7.57 (1H, td, J = 8.3, 1.4, aryl- H ), 7.70 (1H, dd, J = 8.3, 0.7, aryl- H ), 7.95 (1H, dd, J = 8.4, 0.6, aryl- H ).…”

Synthesis of Tacrine Analogues and Their Structure-Activity Relationships

“…41) became more popular [38][39][40]. Many workers have chosen this route [37,[41][42][43][44][45]. Activation of most substances (26) is usually brought about by POCl 3 [25,38,40,41] to give 39 (X=Cl) [50,51], although some workers favour a mixture of POCl 3 with PCl 5 [23,27].…”

“…Several other early studies involved different analogues of tacrine, but these were not tested for activity on acetylcholinesterase. Examples include Plotnikoff et al [67], Patnaik et al [43], Lee [68], and Bindra et al [44]. The synthesis of some of these analogues has been described earlier in this review.…”

“…39, X=Cl, Br) either in traditional solvents (e.g. benzene [37] or phenol [42,44,49]). A catalytic amount of an acidic catalyst has been found advantageous.…”

“…Many substances of general formula 42 (R 2 =Alkyl NH, aryl NH or alkyl 2 N) ( Fig. 11) have been reported [44,[47][48][49]. Most of these contributions were not undertaken in connection with Alzheimers' disease.…”