- TETRAHYDROISOQUINOLINE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION CONTAINING SAME, AND USE THEREOF
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Disclosed are a novel tetrahydroisoquinoline compound, a method for preparing intermediates thereof, a pharmaceutical composition thereof and the use thereof. The tetrahydroisoquinoline compound of the present invention has a good inhibitory effect on phosphodiesterase (PDE4), and can be used in the prevention, treatment or auxiliary treatment of multiple diseases associated with the activity or expression of phosphodiesterase, especially PDE4-associated immune and inflammatory diseases, such as psoriasis and arthritis. (I)
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- Hypervalent Iodine-Mediated Cyclization of Homotryptamine Derivatives
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A facile and efficient cyclization of homotryptamines and their derivatives has been established for the construction of 4a-chlorotetrahydropyrido[2,3-b]indoles and 3,3-spirocyclic 3H-indoles using hypervalent iodine (1-chloro-1,2-benziodoxol-3-one) under mild conditions. The broad substrate scope and successful gram-scale experiment grant this metal-free transformation great potential for further application.
- Jiang, Xinpeng,Zhu, Weijie,Yang, Liechao,Zheng, Zicong,Yu, Chuanming
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supporting information
p. 2268 - 2274
(2019/04/03)
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- Indole-derived psammaplin a analogues as epigenetic modulators with multiple inhibitory activities
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A SAR study has been carried out around a modified scaffold of the natural product psammaplin A obtained by replacing the o-bromophenol unit by an indole ring. A series of indole psammaplin A constructs were generated in a short synthetic sequence that starts with the functionalization of the C3 indole position with in situ generated nitrosoacrylate, and this is followed by protection of the β-indole-α-oximinoesters, saponification, condensation with symmetrical diamines, and deprotection. Biochemical and cellular characterization using U937 and MCF-7 cells confirmed that many of these analogues displayed more potent actitivies than the parent natural product. Moreover, in addition to the reported HDAC and DNMT dual epigenetic inhibitory profile of the parent compound, some analogues, notably 4a (UVI5008), also inhibited the NAD+-dependent SIRT deacetylase enzymes. The SAR study provides structural insights into the mechanism of action of these multiple epigenetic ligands and paves the way for additional structural exploration to optimize their pharmacological profiles. Because of their multi(epi)target features and their action in ex vivo samples, the indole-based psammaplin A derivatives are attractive molecules for the modulation of epigenetic disorders.
- Pereira, Raquel,Benedetti, Rosaria,Pérez-Rodríguez, Santiago,Nebbioso, Angela,García-Rodríguez, José,Carafa, Vincenzo,Stuhldreier, Mayra,Conte, Mariarosaria,Rodríguez-Barrios, Fátima,Stunnenberg, Hendrik G.,Gronemeyer, Hinrich,Altucci, Lucia,De Lera, ángel R.
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p. 9467 - 9491
(2013/01/16)
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- PPAR active compounds
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Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.
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- PPAR ACTIVE COMPOUNDS
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Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.
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Page 131-132
(2008/06/13)
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