Design and synthesis of bioactive adamantane spiro heterocycles

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].

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“…The IC 50 (mM) value at drug concentration 5 mg/mL was~20 [10]. Compound 12 had higher detected inhibitory activity than its analogs 13a-c.…”

Section: Antiparasite Activitymentioning

confidence: 95%

“…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].…”

mentioning

confidence: 99%

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

Shokova

Ковалев

2016

Pharm Chem J

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“…The in vivo antiviral activity of 3-piperidine derivative A against Japanese influenza A 2 was found to be approximately the same as that of 1-adamantanamine. 7 4-Piperidine derivative B proved to display significant anti-influenza A (H3N2) and trypanocidal activity, 8 while piperazine C likewise inhibited H3N2 influenza A virus replication. 9 The (S)-enantiomer of acethydroxamic acid D was the most effective in a study of the trypanidical activities of hydroxamic acid-based derivatives.…”

Section: Introductionmentioning

confidence: 99%

Alternative conditions for the synthesis of novel spiro[1,3-N,N-heterocyclic-adamantanes]

Miklós¹,

Petrisor²,

Fülöp³

2015

Arkivoc

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A series of new spiro[N-heterocyclic-adamantanes] was synthesized through the reaction of 2-adamantanone with β-amino carboxamides. Depending on the chemical and physical characteristics of the starting compounds, the cyclocondensations proceeded under simple and mild (aqueous, solvent-free, ball-milling or/and microwave-assisted) conditions with no necessity for chromatographic purification of the products. The reaction was extended to leucinamide and salicylamide.

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“…Moreover, among various substituents, adamantyl derivatives are gaining importance in well known drugs like Rimantadine, Memantine, Adapalene, Adatanserine and others in clinical trials [7,8]. The adamantyl derivatives are also recognized for their activity against influenza [9] and HI viruses [10]. Some other adamantyl derivatives have been used as anti-inflammatory [11,12], antimicrobial [13,14], antimalarial [15], and antidepressant agents [16] as well as inhibitors of 11β -hydroxysteroid dehydrogenase type 1 (11β -HSD1) [17].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Structure and Antiproliferative Activity of 6-Adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

Khan

Akhtar

Yasin

et al. 2010

Zeitschrift Für Naturforschung B

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A series of 3,6-disubstituted [1,2,4]triazolo [3,4-b][1,3,4]thiadiazoles 5a -l bearing an adamantyl moiety were synthesized by condensation of 4-amino-5-aryl-2H-1,2,4-triazole-3(4H)-thiones 4a -l with adamantyl-1-carboxylic acid in the presence of POCl 3 . The structures of the newly synthesized compounds were established using spectroanalytical techniques and verified further by the crystal structure determination of compounds 5a and 5j. The compounds were screened for their antiproliferative activity against a large panel of human cell lines.

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Design and synthesis of bioactive adamantane spiro heterocycles

Cited by 91 publications

References 28 publications

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

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

Alternative conditions for the synthesis of novel spiro[1,3-N,N-heterocyclic-adamantanes]

Synthesis, Crystal Structure and Antiproliferative Activity of 6-Adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

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