The present invention provides stable metastin derivatives having excellent biological activities (a cancer metastasis suppressing activity, a cancer growth suppressing activity, a gonadotropic hormone secretion stimulating activity, sex hormone secretion stimulating activity, etc.).
By substituting the constituent amino acids of metastin with specific amino acids, the metastin derivatives of the present invention achieve more improved blood stability, solubility, etc., reduced gelation tendency, improved pharmacokinetics, as well as exhibit an excellent cancer metastasis suppressing activity or a cancer growth suppressing activity. The metastin derivatives of the present invention also have a gonadotropic hormone secretion suppressing activity, sex hormone secretion suppressing activity, etc.
Phosphine-Promoted Synthesis of 9<i>H</i>-Pyrrolo[1,2-<i>a</i>]indole Derivatives via an γ-Umpolung Addition/Intramolecular Wittig Reaction
作者:Charlotte Lorton、Arnaud Voituriez
DOI:10.1021/acs.joc.8b00457
日期:2018.5.18
The synthesis of substituted 9H-pyrrolo[1,2-a]indole products from 1H-indole-2-carbaldehydes and allenoates is described, using a phosphine-promoted Michael addition/intramolecular Wittig reaction. This halide- and base-free methodology provides an efficient access to different tricyclic nitrogen-containing heterocycles (18 examples, 32–88% isolated yields).
描述了使用膦促进的迈克尔加成/分子内Wittig反应从1 H-吲哚-2-甲醛和脲基甲酸酯合成取代的9 H-吡咯并[1,2- a ]吲哚产物。这种无卤无碱的方法可以有效地获得不同的三环含氮杂环(18个实例,分离产率为32%至88%)。
Construction of Bridged Aza- and Oxa-[<i>n</i>.2.1] Skeletons via an Intramolecular Formal [3+2] Cycloaddition of Aziridines and Epoxides with Electron-Deficient Alkenes
intramolecular formal [3+2] cycloaddition of activated aziridines and epoxides with electron-deficient alkene has been developed for the general and efficient construction of bridged aza- and oxa-[n.2.1] (n = 3 or 4) skeletons. This strategy can be efficiently promoted by lithium iodide. To demonstrate its potential, the intramolecular formal [3+2] cycloaddition was used to access the important intermediate of homoepiboxidine
The present invention provides a metastin derivative in which the amino acids comprising metastin were modified by alternative chemical substituents resulting in metastin derivatives, having excellent blood stability and exhibiting cancer metastasis inhibiting action or cancer growth inhibiting action.