Serotonergic ergoline derivatives

Mantegani, Sergio; Brambilla, Enzo; Caccia, C.; Damiani, Gabriele; Fornaretto, M. G.; McArthur, Robert A.; Varasi, Mario

doi:10.1016/s0960-894x(98)00166-8

Cited by 7 publications

(7 citation statements)

References 7 publications

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“…6 One particularly interesting example that illustrates the potential of A ring derivatives is the difference in 5-hydroxytryptamine (5-HT, serotonin) receptor selectivities for compounds 8 and 9. 7 Compounds of type 8, which contain a tert-butyl group on C(13), exhibit a selectivity for the 5-HT IA receptor. Molecules of type 9, on the other hand, which possess a tert-butyl group on C(14), show selectivity for the 5-HT 2 family of receptors.…”

Section: Introductionmentioning

confidence: 99%

“…For example, the synthesis of 8 and 9 was accomplished by electrophilic alkylation of the aryl ring by exposing a synthetic intermediate to tert-butyl cation, followed by separation of the regioisomers (Scheme 1). 7 When the methyl lysergate derivative 10, which contains a thiomethyl residue to protect the more electrophilic 2-position of the indole, was exposed to a mixture of tert-butyl acetate and trifluoroacetic acid, it gave rise to 11 (65%) and 12 (15%). A strategy in which the indole is constructed with the appropriate substitution would offer an advantage in the synthesis of compounds containing substituents on C(12)-C(14).…”

Section: Introductionmentioning

confidence: 99%

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Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

2005

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Through a novel sequence of aminodiene Diels-Alder reactions, several substituted amidofurans were readily converted to tricyclic ketones in good yield. The formation of the tricyclic ketone system is the result of a ring opening and dehydration of a transient oxabicyclic adduct formed by an intramolecular Diels-Alder cycloaddition of an amidofuran with a cyclohexenone moiety tethered such that it participates in the cycloaddition as the 2pi component. A convenient way to construct the cyclohexenone is to make use of some aminodiene chemistry developed by Rawal. An angular carbomethoxy group is required in order to activate the olefin toward cycloaddition with Rawal's diene. The presence of this activating group not only prevents the isomerization of the advanced ergoline intermediate to a naphthalene but can also be leveraged for an oxidation to provide Uhle's ketone (13). The easily formed Kornfeld ketone analogue 25 was readily transformed into the corresponding triflate 41 by the action of triflic anhydride and a base. Oxidative addition of vinyl triflate 41 to Pd(0) and the ability of the resulting vinyl palladium species to undergo cross-coupling with terminal alkynes prompted us to devise an expeditious route to lysergic acid. Unfortunately, our inability to carry out a regioselective Heck reaction using vinyl triflate 41 and the methylene amino acrylate ester 48 thwarted the completion of the synthesis of lysergic acid.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

2005

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“…In a previous report, we delineated the synthesis of lysergine ( 3 ) via a radical cyclization/fragmentation strategy, also starting from an indole fragment . In order to prepare ergot alkaloid analogues with substituents on the phenyl ring to optimize their affinity and selectivity at 5-HT receptor subtypes, we investigated the potential of forging the indole ring at a late stage in the synthesis. An intramolecular dearomatizing [3 + 2] annulation reaction to furnish 3,4-fused indole skeletons developed by Murakami and co-workers attracted our attention, which has been used for the synthesis of racemic Uhle’s ketone, a precursor for ergot alkaloids .…”

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confidence: 99%

Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity

2017

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“…The structural correlation between LSD and apomorphine and the involvement of dopamine and serotonin in the pharmacology of hallucinogens has been reviewed by Nichols in 1976 [56]. Newer serotonergic ergoline derivatives have been prepared [57] and evaluated [58].…”

Section: Ergot Alkaloidsmentioning

confidence: 99%

Dopamine Agonists in the Treatment of Parkinsons Disease-Past, Present and Future

Sit

2000

CPD

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An attempt is made by the author to highlight the important events that laid the foundation of dopamine agonists as a treatment strategy for Parkinson s disease. This debilitating neurodegenerative disorder is long recognized as a result of progressive cell loss in the substantia nigra of the midbrain. The destruction of dopaminergic neurons with projections to the striatum results in the diminishing striatal dopamine levels. Anticholinergic drugs were once widely used to counteract the relative overactivity of cholinergic output from the basal ganglia and the strategy was only met with limited success. The discovery of dopamine depletion and the use of levodopa - a dopamine metabolic precursor, led the way to dopamine replacement therapy . The initial success with levodopa was soon overshadowed by the long-term side effects associated with levodopa. Many new drugs were developed with the hope to replace or strengthen the usefulness of levodopa. Apomorphine and ergot alkaloids have been around for some time; they are recently joined by newer dopamine agonists such as ropinirole and pramipexole. Each of these has its own characteristics and has occupied a place in the pharmacotherapy of Parkinson s disease. In this review older aporphines and ergot alkaloids are discussed first. More emphasis is directed to the side-effect profiles, metabolism and pharmacokinetics in terms of their unique chemical structures. The most recent agonists will be briefly discussed before we move on to the future - the future of emerging novel classes of promising dopaminergic agonists.

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Serotonergic ergoline derivatives

Cited by 7 publications

References 7 publications

Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity

Dopamine Agonists in the Treatment of Parkinsons Disease-Past, Present and Future

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