Synthesis of amphiphilic diacyl derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one

Veremeeva, Polina N.; Bovina, Evgenia M.; Grishina, I. A.; Лаптева, В. Л.; Palyulin, Vladimir A.; Зефиров, Н. С.

doi:10.1016/j.mencom.2018.01.006

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…N,N′-Diacyl bispidines have found various different applications in: medicinal chemistry [26] (a review), [27,28]; crystal engineering [29]; macroheterocycle synthesis [13,[18][19][20]23,[29][30][31]; secondary structure nucleators in peptides [22,32]; conformational switching [12,13]; lipid bilayer modifiers [15,33].…”

Section: Anti-syn-mentioning

confidence: 99%

Bispidine Platform as a Tool for Studying Amide Configuration Stability

et al. 2022

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In this work, the solution conformations of seventeen 3,7-diacyl bispidines were studied by means of NMR spectroscopy including VT NMR experiments. The acyl groups included alkyl, alkenyl, aryl, hetaryl, and ferrocene moieties. The presence of syn/anti-isomers and their ratios were estimated, and some reasons explaining experimental facts were formulated. In particular, all aliphatic and heterocyclic units in the acylic R(CO) fragments led to an increased content of the syn-form in DMSO-d6 solutions. In contrast, only the anti-form was detected in DMSO-d6 and CDCl3 in the case when R = Ph, ferrocenyl, (R)-myrtenyl. In the case of a chiral compound derived from the natural terpene myrtene, a new dynamic process was found in addition to the expected inversion around the amide N-C(O) bond. Here, rotation around the CO-C=C bond in the acylic R fragment was detected, and its energy was estimated. For this compound, ΔG for amide N-C(O) inversion was found to be equal to 15.0 ± 0.2 kcal/mol, and for the rotation around the N(CO)–C2′ bond, it was equal to 15.6 ± 0.3 kcal/mol. NMR analysis of the chiral bispidine-based bis-amide was conducted for the first time. Two X-ray structures are reported. For the first time, the unique syn-form was found in the crystal of an acyclic bispidine-based bis-amide. Quantum chemical calculations revealed the unexpected mechanism for amide bond inversion. It was found that the reaction does not proceed as direct N-C(O) bond inversion in the double-chair (CC) conformation but rather requires the conformational transformation into the chair–boat (CB) form first. The amide bond inversion in the latter requires less energy than in the CC form.

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Section: Anti-syn-mentioning

confidence: 99%

Bispidine Platform as a Tool for Studying Amide Configuration Stability

et al. 2022

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“…Эта структура была открыта в середине 60-х годов прошлого века при изучении роли фосфолипидов в свертывании крови [18]. Липосомы являются одним из наиболее распространенных типов наноносителей, используемых в системах для адресной доставки лекарственных средств [19][20][21]. Кроме того, разрабатываются так называемые «флипосомы» -липосомы со встроенными в липидный бислой веществами -молекулярными переключателями, реагирующими, к примеру, на изменение pH среды или температурных условий в заданной области.…”

Section: виды наноразмерных лекарственных средств и их носителейunclassified

“…Кроме того, разрабатываются так называемые «флипосомы» -липосомы со встроенными в липидный бислой веществами -молекулярными переключателями, реагирующими, к примеру, на изменение pH среды или температурных условий в заданной области. В результате изменения внешних условий (pH или температуры) происходит конформационный переход молекулярного переключателя, что приводит к разрыву липидного бислоя и высвобождению инкапсулированного вещества [21]. В настоящее время проводятся клинические испытания термочувствительных липосом с доксорубицином (ThermoDox ® ), высвобождающих активную субстанцию при локальном нагреве тканей сверхвысокочастотным излучением [20].…”

Section: виды наноразмерных лекарственных средств и их носителейunclassified

Nanoscale Therapeutic System: Safety Assessment Features

Bovina¹,

Романов²,

Казаков

et al. 2019

Bezopasnost' i risk farmakoterapii

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Nanoscale drugs differ in special physicochemical, biological, pharmacokinetic parameters. These properties can be used to provide targeted delivery, prolong the action of drugs, as well as reduce their side effects. An important problem that needs attention is the study of the potential risks arising from the treatment of such drugs. The aim of the study: analysis of the requirements of domestic and foreign regulators for the safety of nanoscale drugs. The paper presents the classification of the most promising nanosystems containing drugs, and an analysis of the existing principles for assessing their safety in Russia and abroad has been carried out. It was shown that when assessing the safety of nano-sized drugs, along with the properties of the active substance, it is necessary to take into account the properties of the nanosystem (polymer coating, carrier, etc.), related to its size, distribution pattern, charge of nanoparticles, and ability to induce oxidative stress. Domestic and foreign regulatory documents governing the procedure for assessing the safety of pharmacological substances derived from nanotechnology was analyzed. Conclusions: Despite the availability of recommendations from regulatory authorities, further improvement of the requirements for registration and safety assessment of nanoscale drugs is necessary. Further development of the regulatory framework governing the development, quality, efficiency and safety of nanomaterials in medicine is necessary, taking into account the structural issues of the active substance and nano-carriers.

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“…The variation of amino groups allows a broad tuning of the conformational equilibrium, and the basicity of amino functions could be adjusted for a conformational response within a selected range of pH . Other cyclic and noncyclic scaffolds and more complex molecular devices were also suggested recently as pH‐sensitive conformational switches for similar applications …”

Section: Introductionmentioning

confidence: 99%

Exploration of trans‐2‐(azaarylsulfanyl)‐cyclohexanols as potential pH‐triggered conformational switches

Ruyonga

Mendoza

Browne

et al. 2020

J of Physical Organic Chem

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A series of trans‐2‐(azaarylsulfanyl)‐cyclohexanols, structurally similar to previously studied trans‐2‐aminocylohexanols, have been synthesized and explored as conformational pH triggers. 1H NMR spectroscopy was used to estimate the position of the chair‐chair conformational equilibrium and its acid‐induced shift towards the conformer with the azaarylsulfanyl and hydroxy groups in equatorial positions due to an intramolecular hydrogen bond and electrostatic interactions. Such acid‐induced transition may be used to control the geometry‐dependent molecular properties. The 1H NMR titration curves were used for estimation of the pKa values of protonated compounds that varied from 2.8 to 4.3 (in d4‐methanol) depending on the structure of the azaarylsulfanyl group.

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Synthesis of amphiphilic diacyl derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one

Cited by 5 publications

References 15 publications

Bispidine Platform as a Tool for Studying Amide Configuration Stability

Bispidine Platform as a Tool for Studying Amide Configuration Stability

Nanoscale Therapeutic System: Safety Assessment Features

Exploration of trans‐2‐(azaarylsulfanyl)‐cyclohexanols as potential pH‐triggered conformational switches

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