Use of adamantanecarboxylic acid for the modification of drugs and biologically active compounds (review)

Kovtun, V. Yu.; Plakhotnik, V. M.

doi:10.1007/bf00759430

Cited by 18 publications

(6 citation statements)

References 52 publications

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“…26 Even more popular pharmaceuticals tested with adamantane “add-on” building blocks were Penicillin to give 30 (“Adamantocilin”) and Dopamine to furnish 31 (or “Dopamintine”). 97 More recent examples for the “add-on” strategy of modifications of a primary pharmacophor with the adamantane “lipophilic bullet” acting as a functional subunit, sometimes more suitably described as a “secondary pharmacophor”, include glycolipids. Amongst other lipophilic residues, the 2-(1-adamantyl)ethyl group in the 1-thio-β- L -fucopyranosyllipid 32 was utilized to modify the potency of these compounds that can be used as immunologic adjuvants.…”

Section: “Add-on” To Known Pharmaceuticalsmentioning

confidence: 99%

The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

Wanka¹,

Iqbal²,

Schreiner³

2013

Chem. Rev.

580

475

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Section: “Add-on” To Known Pharmaceuticalsmentioning

confidence: 99%

The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

Wanka¹,

Iqbal²,

Schreiner³

2013

Chem. Rev.

580

475

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“…In spite of that, adamantane is considered in medicinal chemistry a “lipophilic bullet,” and as such it has been used according to an “add-on” strategy to known pharmaceuticals or as a replacement for other lipophilic groups (Wanka et al, 2013 ). This group has been added, among the others, to antidiabetic drugs (Gerzon et al, 1963 ), anabolic steroids (Rapala et al, 1965 ), antimalarials (Gerzon and Kau, 1967 ), and also penicillins (Kovtun and Plakhotnik, 1987 ). None of these experimental derivatives has reached the clinic, however in many cases a considerable improvement of the activity was obtained.…”

Section: Medicinal Chemistry For Antituberculosis Drugs: Mind the Fatmentioning

confidence: 99%

Challenging the Drug-Likeness Dogma for New Drug Discovery in Tuberculosis

et al. 2018

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The emergence of multi- and extensively drug resistant tuberculosis worldwide poses a great threat to human health and highlight the need to discover and develop new, effective and inexpensive antituberculosis agents. High-throughput screening assays against well-validated drug targets and structure based drug design have been employed to discover new lead compounds. However, the great majority fail to demonstrate any antimycobacterial activity when tested against Mycobacterium tuberculosis in whole-cell screening assays. This is mainly due to some of the intrinsic properties of the bacilli, such as the extremely low permeability of its cell wall, slow growth, drug resistance, drug tolerance, and persistence. In this sense, understanding the pathways involved in M. tuberculosis drug tolerance, persistence, and pathogenesis, may reveal new approaches for drug development. Moreover, the need for compounds presenting a novel mode of action is of utmost importance due to the emergence of resistance not only to the currently used antituberculosis agents, but also to those in the pipeline. Cheminformatics studies have shown that drugs endowed with antituberculosis activity have the peculiarity of being more lipophilic than many other antibacterials, likely because this leads to improved cell penetration through the extremely waxy mycobacterial cell wall. Moreover, the interaction of the lipophilic moiety with the membrane alters its stability and functional integrity due to the disruption of the proton motive force, resulting in cell death. When a ligand-based medicinal chemistry campaign is ongoing, it is always difficult to predict whether a chemical modification or a functional group would be suitable for improving the activity. Nevertheless, in the “instruction manual” of medicinal chemists, certain functional groups or certain physicochemical characteristics (i.e., high lipophilicity) are considered red flags to look out for in order to safeguard drug-likeness and avoid attritions in the drug discovery process. In this review, we describe how antituberculosis compounds challenge established rules such as the Lipinski's “rule of five” and how medicinal chemistry for antituberculosis compounds must be thought beyond such dogmatic schemes.

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“…The latter can also be formed, along with adamantane 1, due to the intermolecular transfer of the hydride ion from 2-hydroxyadamantane (6) to the cation 3. The reaction of 1-methyladamantane (8) with 96% sulfuric acid at 80 o C leads to a complex mixture of products in which 5-methyladamantan-2-one (9) is the major component. 19 In systems containing a strong mineral acid (H 2 SO 4 , HNO 3 ) and trifluoroacetic anhydride, the role of the hydride ion acceptor is probably played by the cations HSO 3 or NO 2 , which are generated in situ from the corresponding acids and weakly nucleophilic trifluoroacetic anhydride.…”

Section: Substitution Reactions In the Adamantane Series In Electroph...mentioning

confidence: 99%

“…7,8 It was found that introduction of an adamantyl fragment into medical compounds enhances their biological activities owing to the higher fatsolubility. 6,9 Some adamantane derivatives exhibit antiviral activities, e.g., 1-aminoadamantane and 1-ethylaminoadamantane hydrochlorides, which are the active principles of antiviral Mydantan and Remantadinum manufactured by the pharmaceutical plant in Olaine, Latvia.…”

Section: Introductionmentioning

confidence: 99%