- SELECTIVE ESTROGEN RECEPTOR DEGRADERS AND USES THEREOF
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The present disclosure provides compounds of Formula (I) and Formula (II). The compounds described herein may be useful in treating proliferative diseases (e.g., cancer).Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
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Paragraph 00152; 00155; 00156
(2017/12/28)
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- Alpha-ethyltryptamines as dual dopamine-serotonin releasers
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The dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporter releasing activity and serotonin-2A (5-HT2A) receptor agonist activity of a series of substituted tryptamines are reported. Three compounds, 7b, (+)-7d and 7f, were found to be potent dual DA/5-HT releasers and were >10-fold less potent as NE releasers. Additionally, these compounds had different activity profiles at the 5-HT2Areceptor. The unique combination of dual DA/5-HT releasing activity and 5-HT2Areceptor activity suggests that these compounds could represent a new class of neurotransmitter releasers with therapeutic potential.
- Blough, Bruce E.,Landavazo, Antonio,Partilla, John S.,Decker, Ann M.,Page, Kevin M.,Baumann, Michael H.,Rothman, Richard B.
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supporting information
p. 4754 - 4758
(2015/01/09)
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- Synthesis and structureactivity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands
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5-Hydroxytryptamine 6 receptors (5-HT6R) are being perceived as the possible target for treatment of cognitive disorders as well as obesity. The present article deals with the design, synthesis, in vitro binding and structureactivity relationship of a novel series of tetracyclic tryptamines with the rigidized N-arylsulphonyl, N-arylcarbonyl and N-benzyl substituents as 5-HT6 receptor ligands. The chiral sulphonyl derivatives 15a and 17a showed high affinity at 5-HT6R with the Ki of 23.4 and 20.5nM, respectively. The lead compound from the series 15a has acceptable ADME properties, adequate brain penetration and is active in animal models of cognition like Novel Object Recognition Task (NORT) and water maze.
- Nirogi, Ramakrishna V.S.,Kambhampati, Ramasastri,Kothmirkar, Prabhakar,Konda, Jagadishbabu,Bandyala, Thrinath Reddy,Gudla, Parandhama,Arepalli, Sobhanadri,Gangadasari, Narasimhareddy P.,Shinde, Anil K.,Deshpande, Amol D.,Dwarampudi, Adireddy,Chindhe, Anil K.,Dubey, Pramod Kumar
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scheme or table
p. 443 - 450
(2012/08/28)
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- Spirotetrahydro β-carbolines (spiroindolones): A new class of potent and orally efficacious compounds for the treatment of malaria
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The antiplasmodial activity of a series of spirotetrahydro β-carbolines is described. Racemic spiroazepineindole (1) was identified from a phenotypic screen on wild type Plasmodium falciparum with an in vitro IC50 of 90 nM. Structure-activity relationships for the optimization of 1 to compound 20a (IC50 = 0.2 nM) including the identification of the active 1R,3S enantiomer and elimination of metabolic liabilities is presented. Improvement of the pharmacokinetic profile of the series translated to exceptional oral efficacy in the P. berghei infected malaria mouse model where full cure was achieved in four of five mice with three daily doses of 30 mg/kg.
- Yeung, Bryan K. S.,Zou, Bin,Rottmann, Matthias,Lakshminarayana, Suresh B.,Ang, Shi Hua,Leong, Seh Yong,Tan, Jocelyn,Wong, Josephine,Keller-Maerki, Sonja,Fischli, Christoph,Goh, Anne,Schmitt, Esther K.,Krastel, Philipp,Francotte, Eric,Kuhen, Kelli,Plouffe, David,Henson, Kerstin,Wagner, Trixie,Winzeler, Elizabeth A.,Petersen, Frank,Brun, Reto,Dartois, Veronique,Diagana, Thierry T.,Keller, Thomas H.
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scheme or table
p. 5155 - 5164
(2010/09/05)
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- α-Methyltryptamine sulfonamide derivatives as novel glucocorticoid receptor ligands
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α-Methyltryptamine sulfonamides were identified as human glucocorticoid receptor (hGR) ligands in an ultra high throughput screening (UHTS) campaign. Described will be the hit-to-lead activities, including parallel and single point analog synthesis to map the scaffold. Ligands were identified that exhibited 30 nM binding to hGR. The SAR and selectivity of these compounds will be discussed.
- Marshall, Daniel R.,Rodriguez, Gus,Thomson, David S.,Nelson, Richard,Capolina, Allison
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p. 315 - 319
(2007/10/03)
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