- Construction of NH-Unprotected Spiropyrrolidines and Spiroisoindolines by [4+1] Cyclizations of γ-Azidoboronic Acids with Cyclic N-Sulfonylhydrazones
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The reactions of N-sulfonylhydrazones derived from cyclic ketones with γ-azidopropylboronic acid and 2-(azidomethyl)phenylboronic acid give rise to spirocyclic pyrrolidines and spiroisoindolines, respectively. The reactions proceed without the need of any transition-metal catalyst through a domino process that comprises the formation of a Csp3-C and a Csp3-N bond of the former hydrazonic carbon. The scope of the reaction has been explored by the preparation of over 50 examples of NH-unprotected spirocyclic derivatives. Importantly, this methodology could be applied for the preparation of alkaloid steroids from steroid N-tosylhydrazones.
- Cabal, María-Paz,López, Lucía,Valdés, Carlos
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supporting information
(2021/12/09)
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- Discovery of a novel bicyclic compound, DS54360155, as an orally potent analgesic without mu-opioid receptor agonist activity
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We synthesized derivatives of a natural alkaloid, conolidine, and evaluated these derivatives in the acetic acid-induced writhing test and formalin test in ddY mice after oral administration. As a result, we identified (5S)-6-methyl-1,3,4,5,6,8-hexahydro-7H-2,5-methano[1,5]diazonino[7,8-b]indol-7-one sulfate salt, 15a (DS54360155), with a unique and original bicyclic skeleton, as an analgesic more potent than conolidine. Moreover, 15a did not exhibit mu-opioid receptor agonist activity.
- Arita, Tsuyoshi,Asano, Masayoshi,Kubota, Kazufumi,Domon, Yuki,Machinaga, Nobuo,Shimada, Kousei
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supporting information
(2019/11/11)
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- THE USE OF N-ARYL DIAZASPIRACYCLIC COMPOUNDS IN THE TREATMENT OF ADDICTION
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Compounds, compositions and methods for treating drug addiction, nicotine addiction, and/or obesity are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteraryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds are effective at inhibiting dopamine production and/or secretion, and accordingly are effective at inhibiting the physiological "reward" process that is associated with ingestion of nicotine and/or illicit drugs. The compounds and compositions can be administered in effective amounts to inhibit dopamine release, wihout resulting in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).
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Page/Page column 58
(2010/10/20)
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