- Binding of β-carbolines at 5-HT2 serotonin receptors
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A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4-tetrahydro-β-carbolines was examined at 5-HT2A and 5-HT2C serotonin receptors. Whereas most of the methoxy-substituted derivatives typically displayed affinities similar to their unsubstituted parents, certain (particularly 8-substituted) bromo derivatives displayed enhanced affinity. A binding profile was obtained for selected β-carbolines.
- Grella, Brian,Teitler, Milt,Smith, Carol,Herrick-Davis, Katharine,Glennon
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Read Online
- TAU-PROTEIN TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of tan protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tan protein, such that tan protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tan. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tan protein. Diseases or disorders that result from aggregation or accumulation of tan protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 2274; 2275
(2021/02/12)
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- Tetrahydrocarboline analogs as MCH-1 antagonists
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A new series of tetrahydrocarbolines with potent MCH-1 antagonist activity were synthesized, using a conformationally constrained design approach towards optimizing pharmacokinetic properties. Two compounds from this series were progressed to a 5-day diet-induced obesity mouse screening model to evaluate their potential as weight loss agents. Both compounds produced a highly significant reduction in weight, which was attributed to their improved pharmacokinetic profile.
- Henderson, Alan J.,Deering, Dustin,Grabowski, James F.,Hadden, Mark,Jiang, Xiaowu,Khmelnitsky, Yuri,Luche, Michele,Surman, Matthew D.,Cheetham, Sharon,Vickers, Steven,Viggers, Jean,Guzzo, Peter R.
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scheme or table
p. 7024 - 7028
(2011/01/05)
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- Synthesis of didemnolines A-D, N9-substituted β-carboline alkaloids from the marine ascidian Didemnum sp.
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Didemnolines A-D (1-4) were synthesized and their structures were confirmed through comparisons of data for the synthetic material with those obtained for natural 1-4. The synthesis of didemnolines A (1) and C (3) involved the coupling of 1-[(benzyloxy)methyl]-4-chloromethyl-5- (thiomethyl)imidazole (6) with 7-bromo-β-carboline (5), while didemnolines B (2) and D (4) were formed through the analogous coupling of 6 with norharmon (7). Intermediate 6 was efficiently prepared from 1-[(benzyloxy)methyl]- 2,4,5-tribromoimidazole using a sequential one-pot halogen-metal exchange reaction and 7-Br-β-carboline was synthesized using a new approach.
- Schumacher, Robert W.,Davidson, Bradley S.
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p. 935 - 942
(2007/10/03)
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