Biological Activity of Adamantane-Containing Mono- and Polycyclic Pyrimidine Derivatives* (A Review)

Abstract

Biological test results for a series of adamantane-containing pyrimidines, purines, and their derivatives that were synthesized and studied in 1999 -2001 are reviewed. Pyrimidine, purine, and similar scaffolds are exceedingly common key building blocks in the design of drugs with the broadest spectra of action comprising antibacterial, antiviral, antitumor, neurotropic, antifungal, immunotropic, and other types of drugs. An adamantane moiety in the molecules often has a substantial effect on the biological properties. Practically all studies included in the first part of the present review [1] explain their goals using just such factors. Therefore, almost every study consisted of two parts, i.e., chemical and biological.The previous studies focused on synthetic pyrimidine derivatives such as monocyclic pyrimidines (pyrimidinone, uracil, cytosine, uridines, etc.), condensed di-and polycyclic compounds (pyrazolopyrimidine, triazolopurine, xanthene, etc.), and adenosines with various substitution patterns and types of substituents. An adamantane moiety could be either bonded directly to the heterocycle or on its periphery. This part of the review focuses on biological tests of the synthesized compounds**. The subsections present research results according to individual type of biological activity. In addition, a subsection called Biological Screening was included. It includes results for instances where the activity of certain rather large groups (types) of compounds was studied for several rather than a single indication. This was most often related to characteristic antimicrobial, fungicidal, and antimalarial activity and the cytotoxicity of the drugs. In most instances, we considered it counterproductive to lump these results into piles in various sections. * Part 1 of the present review [1] contains information regarding the synthesis of adamantane-containing pyrimidine derivatives. ** The following terms [abbreviation and its explanation (if it exists) given in the corresponding publication] are used to present the biological test results:MIC, minimum inhibiting concentration [2, 3, 6]. MIC 50 , minimum inhibiting concentration suppressing development of virus-induced cytopathic activity by 50% [23,51]. MCC 50 , minimum cytotoxic concentration causing 50% inhibition of cell growth (VERO cells) [23,51]. CD 50 , cytotoxic dose causing 50% inhibition of cell growth [28]. CC 50 , cytotoxic concentration of a drug required to inhibit 50% of any subject in vitro [3,22]. EC 50 , 50% effective plasma concentration at which the effectiveness is 50% of the maximum for this drug in vivo [3,7,9,22]. ID, inhibiting dose; IC, inhibiting concentration, IC 50 , [5,6,9,10,41]; ID 80 , [3]; ID 95 , [28]. SI, selectivity index; SI = MCC 50 /MIC 50 [23, 51]; SI = CC 50 /EC 50 [3, 22]; SI = CD 50 /ID 50 [28]. pEC 50 , negative logarithm of EC 50 [46]. K i , equilibrium dissociation constant [42, 44, 45].

Synthesis and Evaluation of the Psychotropic Activity of Framework Derivatives of Alpha-Pyrrolidone

“…Monitoring the reaction progress and checking the individuality of the compounds were carried out using TLC (Merck M60 F254 plates; visualization with iodine vapor, UV irradiation, or dilute sulfuric acid). The 1 H and 13 C NMR, DEPT, HMBC, HMQC, and NOESY spectra were recorded with a JEOL JNM-ECX400 spectrometer (Japan) in CDCl 3 and DMSO-d 6 using the residual signal of solvents as an internal standard. Chemical shifts were measured in the δ ppm scale; coupling constants J, in Hz.…”

“…1 H NMR (δ, ppm): 1.55-1.67 (m, 6H, 2CH 2 and 2CH), 1.82 (pseudo-pentet, 2H, J = 7.5, CH 2 ), 2.00-2.12 (m, 9H, 4CH 2 and CH), 2.27 (t, 2H, 3 J = 8.2, CH 2 ), 3.38 (t, 2H, 3 J = 6.8, CH 2 N). 13 C NMR (δ, ppm): 18.2 (CH 2 ), 29.6 (3CH), 33.6 (2CH 2 ), 39.6 (4CH 2 ), 44.8 (2CH 2 ), 55.1 (C), 175.5 (C=O). 3,8 ]undecane-4-carboxylate (1.00 g, 3.63 mmol) in anhydrous THF (20 mL), then the reaction mixture was kept under ultrasonic irradiation in an argon atmosphere for 40 h; the solvent was evaporated, the residue was diluted with water (20 mL), the resulting solution was washed with petroleum ether (2 × 5 mL), pH was adjusted to 3 with 10 M HCl, the resulting emulsion was extracted with CHCl 3 (5 × 3 mL), the organic layers were combined, dried over Na 2 SO 4 , the solvent was evaporated on a rotary evaporator.…”

“…-1.90 (m, 7Н, 7СН HomoAd ), 1.97-2.02 (m, 1Н, СН HomoAd ), 2.04-2.12 (m, 1Н, СН HomoAd ), 2.57-2.65 (m, 2Н, СН 2 COOH), 2.85-2.88 (m, 1Н, СН HomoAd ), 12.05 (s, 1H, ОН) 13. C NMR (δ, ppm): 26.6 (CH), 26.7 (CH), 30.4 (СH 2 ), 31.0 (CH 2 ), 31.5 (СН), 34.4 (CH 2 ), 35.5 (CH 2 ), 36.4 (CH 2 ), 40.2 (CH 2 ), 48.0 (СН), 53.8 (CH), 174.3 (COOH), 216.5 (C=О) (Table…”

A Zinc-Mediated Deprotective Annulation Approach to New Polycyclic Heterocycles

“…The development of efficient methods for the synthesis of high value added polycyclic heterocyclic derivatives by metal-promoted annulation of acyclic precursors is one of the most important area of research in heterocyclic chemistry [ 1 , 2 , 3 , 4 , 5 ]. Polycyclic heterocyclic systems, in fact, are largely present as fundamental cores in natural products and in biologically active compounds [ 6 , 7 , 8 , 9 , 10 , 11 ], and the possibility to obtain them by a simple cyclization process starting from readily available substrates is particularly attractive [ 1 , 2 , 3 , 4 , 5 ].…”

Nascent pharmacological advancement in adamantane derivatives

“…Adamantane-based compounds are reported to possess a plethora of biological activities including antiviral, [37,38] anticancer, [39] antimalarial, [40] antimicrobial, [41] and inhibitors of various enzymes. [42,43] Therefore, in the present review, we have highlighted multiple articles presenting the biological activities of adamantane-based synthetic compounds and their structure-activity relationship study.…”