Medicinal Chemistry of Present and Future MAO-B Inhibitors

Gaál, J.; Hermecz, I.

doi:10.1007/978-3-0348-6348-3_4

Cited by 3 publications

(4 citation statements)

References 98 publications

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“…The Meisenheimer rearrangement of N -oxides is additionally of biological importance. In vivo degradation of the excellent irreversible monoamine oxidase (MAO) inhibitors , (e.g., MAO-A: Clorgyline, Abbott-21.855; MAO-B: Selegiline, Pargyline), essentially tertiary amines with N -propargyl and N -methyl substituents (for individual structures, see Scheme S1 in the Supporting Information), starts with a Meisenheimer rearrangement of the corresponding N -oxides that Selegiline- N -oxide is a very strong neuroprotective agent.…”

Section: Introductionmentioning

confidence: 99%

“…The question arises of how many solvent molecules should be taken into account. If we focus only on the first solvation shell around the N -oxygen of 1 , are one or two or three solvent molecules able to interact with the three nonbonded electron pairs of the negative acceptor oxygen atom? − We carried out computations on models containing zero or one or two solvent molecules of type 2; for one solvent (MeOH), we also computed the model involving three solvent molecules.…”

Section: Introductionmentioning

confidence: 99%

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Modeling Rate-Controlling Solvent Effects. The Pericyclic Meisenheimer Rearrangement of N-Propargylmorpholine N-Oxide

et al. 2005

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The activation parameters of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of N-propargylmorpholine N-oxide were determined by experimental and computational methods. A number of aprotic and protic solvents of different polarities and hydrogen bond-forming abilities and the roles of electron-pair acceptor additives were investigated. The reaction kinetics were followed by means of NMR. In protic solvents, isotope-labeling experiments revealed a novel inverse secondary kinetic isotope effect (k(H)/k(D) about 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) --> C(sp(2)) change in hybridization at the reaction center. In molecular computations at the B3LYP/6-31++G(d,p) level of theory, implicit, explicit, and joint explicit-implicit solvent models were used. The explicit-implicit model and molecular dynamic simulations gave the most accurate results. The components of the rate-controlling solvent effect are discussed, and general equations are proposed for accurate prediction of the solvent-dependent activation parameters.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modeling Rate-Controlling Solvent Effects. The Pericyclic Meisenheimer Rearrangement of N-Propargylmorpholine N-Oxide

et al. 2005

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“…The role of isoenzymes has not been revealed completely yet. though it is known that they influence the regulation of circulation and proper using of biogenic amines (12,13). MAO-A form catabolizes dopamine, sérotonine and norepinephrine.…”

Section: The History Of Amine Oxidase (Mao) Discoverymentioning

confidence: 99%

“…MAO-B is located mostly in striatum and grey matter (mostly in serotonergic neurons). There is more MAO-13 form than MAO-A in the brain (13,15). MAO-A form is present in trophoblast and MAO-B is present in blood platelets and lymphocytes (16).…”

Section: The History Of Amine Oxidase (Mao) Discoverymentioning

confidence: 99%

Historia odkryć enzymów inaktywujących katecholaminy

Tylec¹,

Jarząb²,

Stryjecka-Zimmer³

et al. 2008

Annales UMCS, Medicina

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Propargylamine: an Important Moiety in Drug Discovery

et al. 2023

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Propargylamine is a chemical moiety whose properties have made it a widely distributed group within the fields of medicinal chemistry and chemical biology. Its particular reactivity has traditionally popularized the preparation of propargylamine derivatives using a large variety of synthetic strategies, which have facilitated the access to these compounds for the study of their biomedical potential. This review comprehensively covers and analyzes the applications that propargylamine-based derivatives have achieved in the drug discovery field, both from a medicinal chemistry perspective and from a chemical biology-oriented approach. The principal therapeutic fields where propargylamine-based compounds have made an impact are identified, and a discussion of their influence and growing potential is included.

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Medicinal Chemistry of Present and Future MAO-B Inhibitors

Cited by 3 publications

References 98 publications

Modeling Rate-Controlling Solvent Effects. The Pericyclic Meisenheimer Rearrangement of N-Propargylmorpholine N-Oxide

Modeling Rate-Controlling Solvent Effects. The Pericyclic Meisenheimer Rearrangement of N-Propargylmorpholine N-Oxide

Historia odkryć enzymów inaktywujących katecholaminy

Propargylamine: an Important Moiety in Drug Discovery

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