- Intramolecular Sakurai Allylation of Geminal Bis(silyl) Enamide with Indolenine. A Diastereoselective Cyclization to Form Functionalized Hexahydropyrido[3,4- b]Indole
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A fluoride-promoted intramolecular Sakurai allylation of geminal bis(silyl) enamide with indolenine has been developed. The reaction facilitates an efficient cyclization to give hexahydropyrido[3,4-b]indoles in good yields with high diastereoselectivity. The resulted cis, trans-stereochemistry further enables the ring-closing metathesis (RCM) reaction of two alkene moieties, giving a tetracyclic N-hetereocycle widely found as the core structure in akuammiline alkaloids.
- Chen, Yi,Gao, Lu,Song, Xuanyi,Song, Zhenlei
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supporting information
p. 124 - 128
(2021/01/13)
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- Aromatic heterocyclic derivative and application thereof in medicine
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The invention provides aromatic heterocyclic derivatives or stereoisomers, tautomers, nitrogen oxides, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, which are used for treating Alzheimer's disease. The invention also discloses pharmaceutical compositions containing the compounds and a method for treating Alzheimer's disease by using the compounds or the pharmaceutical compositions provided by the invention.
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Paragraph 0390; 0392-0393
(2020/02/08)
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- Fradcarbazole A compound and preparation method and application thereof
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The invention discloses a fradcarbazole A compound and a preparation method and application thereof. The fradcarbazole A compound is prepared from staurosporine or halogenated staurosporine which is subjected to a sulfur acylation reaction, a salt forming reaction together with iodomethane, a substitution reaction and a dehydrating cyclization reaction. The fradcarbazole A compound has very high selectivity and inhibitory activity on acute myeloid cell strains, namely MV4-11, with Flt3-ITD mutation, has a weak inhibiting effect on human peripheral blood mononuclear cells (PBMC), and can be developed to be an efficient and low-toxicity drug for preventing and treating leukemia.
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Paragraph 0016
(2019/07/01)
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- Semisynthetic Derivatives of Fradcarbazole A and Their Cytotoxicity against Acute Myeloid Leukemia Cell Lines
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Fourteen derivatives of the marine-derived fradcarbazole A were synthesized from staurosporine. Their structures were identified by NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS). The derivatives were screened in vitro for antiproliferative activity against three human leukemic cell lines (MV4-11, HL-60, K562). All of the derivatives displayed cytotoxicity against the human FLT-3 internal tandem duplication (ITD) mutant acute myeloid leukemia (AML) cell line MV4-11 with IC50 values of 0.32-0.96 μM. The mechanism of action studies indicated that the most effective 3-chloro-5"-fluorofradcarbazole A (6) induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G0/G1 phase. Furthermore, compound 6 can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5"-fluorofradcarbazole A (6) is a potential candidate for developing novel anti-AML agents in the future.
- Li, Mingpeng,Xu, Yanchao,Zuo, Mingxing,Liu, Wen,Wang, Liping,Zhu, Weiming
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p. 2279 - 2290
(2019/09/19)
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- Method for preparing spiro2-diazido-indoline
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The invention provides a method for preparing a compound shown in the formula II (please see the formula in the description). The method includes the following step of making indole shown in the formula I (please see the formula in the description) react with a precursor and ceric ammonium nitrate in the inert atmosphere so that spiro2-diazido-indoline can be obtained, wherein the precursor can provide azide groups. In the formula I and the formula II, R1 is selected from at least one of hydrogen, an alkyl group of C1-C5, alkoxy of C1-C5, F, Br and Cl; R2 is an alkyl group of C1-C5; Boc represents t-butyloxycarboryl. The precursor is sodium azide or trimethylsilyl azide. The mole ratio of indole shown in the formula I to the precursor to ceric ammonium nitrate is 1:(2-4):(4-8). According to the simple method, the two azide groups are introduced to the organic molecule, and in other words, spiro2-diazido-indoline is effectively prepared under the effects of the precursor capable of providing the azide groups and ceric ammonium nitrate with indole of different structures as the raw material. The raw material is easy to prepare, the reaction condition is gentle, operation is easy and convenient, and yield can reach 45% at most.
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Paragraph 0047; 0048
(2016/10/09)
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- Cascade annulation reactions to access the structural cores of stereochemically unusual strychnos alkaloids
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A new cascade annulation reaction has been developed to access the core structures of a novel family of strychnos alkaloids with a unique stereochemical arrangement. The new annulation cascade is facilitated by the development of a robust reaction sequenc
- Delgado, Rieardo,Blakey, Simon B.
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supporting information; experimental part
p. 1506 - 1510
(2009/08/16)
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- Novel tetrahydro-β-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)
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A structure-activity relationship study was conducted on a series of tetrahydro-β-carboline-1-carboxylic acid analogs in order to identify the key functionality responsible for activity against the mitogen-activated protein kinase-activated protein kinase 2 enzyme (MK-2). The compounds were further evaluated for their ability to inhibit TNFα production in U937 cells and in vivo. These compounds represent a novel structural class of compounds capable of inhibiting MK-2 with remarkable selectivity.
- Trujillo, John I.,Meyers, Marvin J.,Anderson, David R.,Hegde, Shridhar,Mahoney, Matthew W.,Vernier, William F.,Buchler, Ingrid P.,Wu, Kun K.,Yang, Syaluan,Hartmann, Susan J.,Reitz, David B.
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p. 4657 - 4663
(2008/02/13)
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- N-arylsulfonylindole derivatives as serotonin 5-HT6 receptor ligands
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A series of N1-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT6 receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl in the 2-position of the indole ring (43) can replace the arylsulfonyl substituent in the 1-position with no loss of affinity. This suggested that the binding conformation of the aminoethyl side chain at this receptor was toward the 4-position of the indole ring and was supported by the fact that the 4-(aminoethyl)indoles (45) also displayed high affinity, as did the conformationally rigid 1,3,4,5-tetrahydrobenz[c,d]indole (49). Molecular modeling showed that 19, 43, and 45 all had low-energy conformers that overlaid well onto 49. Both 19 and 49 had good selectivity over other serotonin receptors tested, with 49 also showing excellent selectivity over all dopamine receptors. In a functional adenylate cyclase stimulation assay, 19 and 49 had no agonist activity, whereas 45 behaved as a partial agonist. Finally, it was shown that 19 had good activity in the 5-HT2A centrally mediated mescaline-induced head twitch assay, which implies that it is brain-penetrant.
- Russell,Baker,Barden,Beer,Bristow,Broughton,Knowles,McAllister,Patel,Castro
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p. 3881 - 3895
(2007/10/03)
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