- Cu-Catalyzed Dimerization of Indole Derived Oxime Acetate for Synthesis of Biimidazo[1,2- a]indoles
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A copper-mediated cyclization and dimerization of indole derived oxime acetate was developed to generate a series of biimidazo[1,2-a]indole scaffolds with two contiguous stereogenic quaternary carbons in one step.
- Xie, Tao,Sui, Qi-Bang,Qin, Lu-Zhe,Wen, Xiaoan,Sun, Hongbin,Xu, Qing-Long,Zhen, Le
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supporting information
p. 5518 - 5529
(2021/05/04)
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- Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids
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We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L-tryptophan as the starting material. Two key bridged skeleton-forming reactions, namely tandem sequential oxidative cyclopropanol ring-opening cyclization and ketone α-allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na-methyl-16-epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N-demethylkoumine) with more complex cage scaffolds has been accomplished.
- He, Ling,Jiang, Yan,Qiao, Zhen,Qiu, Hanyue,Su, Xiaojiao,Tan, Qiuyuan,Yang, Jiaojiao,Yang, Zhao,Zhang, Min,Zhou, Wenqiang
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supporting information
p. 13105 - 13111
(2021/05/10)
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- CELL CYCLE PROGRESSION INHIBITOR
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The present invention provides a cell cycle progression inhibitor, a cytostatic agent, and an anticancer agent. The cell cycle progression inhibitor, the cytostatic agent, and the anticancer agent each contains a Hes1 protein-PHB2 protein binding enhancer.
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Paragraph 0076
(2019/09/18)
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- Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors
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Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC50 of 1.230 μM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.
- Liu, Hong-Min,Suo, Feng-Zhi,Li, Xiao-Bo,You, Ying-Hua,Lv, Chun-Tao,Zheng, Chen-Xing,Zhang, Guo-Chen,Liu, Yue-Jiao,Kang, Wen-Ting,Zheng, Yi-Chao,Xu, Hai-Wei
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p. 357 - 372
(2019/05/17)
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- Method for synthesizing indole -3 - formaldehyde compounds (by machine translation)
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The invention relates to a synthetic indole - 3 - formaldehyde compounds, which belongs to the technical field of organic synthesis. The invention will be indole compound, hexamethylene tetramine, crystalline aluminum trichloride, N, N - dimethyl formamide in proportion in 120 °C reaction under the condition of 1 - 20 the H, then filtered, washing, filtering, concentrating, column chromatography purification and other after-treatment technology, make the refined indole - 3 - formaldehyde compound. The invention overcomes the indole - 3 - benzaldehyde compound of preparation need to use not stabilized peroxide, and for a long time under the high temperature reaction of the defect. And the invention uses the advantages of simple equipment, product yield is high, the resulting yield of a target product can be up to 94%. In addition, the invention relates to a low reaction conditions, less catalyst levels, low energy consumption, the post treatment process is simple and easy to use, without the need of using a high dosage of acid or alkali, post-processing the solvent can be recovered and recycled, industrial "three wastes" is discharged little, suitable for large-scale production. (by machine translation)
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Paragraph 0041-0044; 0081-0084
(2018/08/28)
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- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 00874-00875
(2018/11/22)
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- Iron-Catalyzed C3-Formylation of Indoles with Formaldehyde and Aqueous Ammonia under Air
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An efficient iron-catalyzed C3-selective formylation of free (N-H) or N-substituted indoles was developed by employing formaldehyde and aqueous ammonia, with air as the oxidant. This new method gave 3-formylindoles in moderate to excellent yields with fairly short reaction times. Moreover, this procedure for catalytic formylation of indoles can be applied to gram-scale syntheses.
- Wang, Qing-Dong,Zhou, Bin,Yang, Jin-Ming,Fang, Dong,Ren, Jiangmeng,Zeng, Bu-Bing
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supporting information
p. 2670 - 2674
(2017/10/06)
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- Silica-supported ceric ammonium nitrate catalyzed chemoselective formylation of indoles
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Selective formylation of free (N-H) indoles at C3 can be achieved by using formylating species generated from hexamethylenetetramine (HMTA) and silica-supported ceric ammonium nitrate (CAN-SiO2). The use of a catalytic amount of this solid-supported reagent was found to be compatible with a range of substituents on the indoles and generated the corresponding products with good yields. A plausible mechanism for the formylation involving an electron transfer process is discussed.
- Tongkhan, Sukanya,Radchatawedchakoon, Widchaya,Kruanetr, Senee,Sakee, Uthai
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p. 3909 - 3912
(2014/07/08)
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- Chiral anion phase transfer of aryldiazonium cations: An enantioselective synthesis of C3-diazenated pyrroloindolines
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Herein is reported the first asymmetric utilization of aryldiazonium cations as a source of electrophilic nitrogen. This is achieved through a chiral anion phase-transfer pyrroloindolinization reaction that forms C3-diazenated pyrroloindolines from simple tryptamines and aryldiazonium tetrafluoroborates. The title compounds are obtained in up to 99% yield and 96% ee. The air- and water-tolerant reaction allows electronic and steric diversity of the aryldiazonium electrophile and the tryptamine core. Live and let diazene: Chiral anion phase transfer of aryldiazonium cations has been utilized to prepare C3-diazenated pyrroloindolines. The air- and water-tolerant reaction allows electronic and steric diversity in the aryldiazonium electrophile and the tryptamine core, with the products being obtained in up to 99% yield and 96% ee (MTBE=methyl tert-butyl ether).
- Nelson, Hosea M.,Reisberg, Solomon H.,Shunatona, Hunter P.,Patel, Jigar S.,Toste, F. Dean
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supporting information
p. 5600 - 5603
(2014/06/10)
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- Synthesis of indolyl-3-acetonitrile derivatives and their inhibitory effects on nitric oxide and PGE2 productions in LPS-induced RAW 264.7 cells
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Arvelexin is one of major constituents of Brassica rapa that exerts anti-inflammatory activities. Several indolyl-3-acetonitrile derivatives were synthesized as arvelexin analogs and evaluated for their abilities to inhibit NO and PGE2 productions in LPS-induced RAW 264.7 cells. Of the indolyl-3-acetonitriles synthesized, compound 2k, which possesses a hydroxyl group at C-7 position of the indole ring and an N-methyl substituent, more potently inhibited NO and PGE2 productions and was less cytotoxic than arvelexin on macrophage cells.
- Kwon, Tae Hoon,Yoon, Ik Hwan,Shin, Ji-Sun,Lee, Young Hun,Kwon, Bong Jin,Lee, Kyung-Tae,Lee, Yong Sup
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p. 2571 - 2574
(2013/07/04)
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- 1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors
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KDR kinase inhibition is considered to play an important role in regulating angiogenesis, which is vital for the survival and proliferation of tumor cells. Recently we disclosed a structure-based kinase inhibitor design strategy which led to the identification of a new class of VEGFR-2/KDR kinase inhibitors bearing heterocyclic substituted pyrazolones as the core template. Instability in a rat S9 preparation and poor iv PK profiles for most of these inhibitors necessitated exploration of new pyrazolones to identify new analogs with improved metabolic stability. Optimization of the heterocyclic moiety led to the identification of the thiadiazole series of pyrazolones (D) as potent VEGFR-2/KDR kinase inhibitors. SAR modifications, kinase selectivity profiling, and structural elements for improved PK properties were explored. Oral bioavailability up to 29% was achieved in the rat. Modeling results based on the Glide XP docking approach supported our postulation regarding the interaction of the lactam segment of the pyrazolones with the hinge region of the KDR kinase.
- Tripathy, Rabindranath,Ghose, Arup,Singh, Jasbir,Bacon, Edward R.,Angeles, Thelma S.,Yang, Shi X.,Albom, Mark S.,Aimone, Lisa D.,Herman, Joseph L.,Mallamo, John P.
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p. 1793 - 1798
(2007/10/03)
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- Inhibitors of cellular necrosis
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The present invention relates to compounds and pharmaceutical preparations and their use in therapy for preventing or treating trauma, ischemia, stroke and degenerative diseases associated with cell death. Methods and compositions of the invention are particularly useful for treating neurological disorders associated with cellular necrosis.
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Page/Page column 37
(2008/06/13)
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- Effects of indole fatty alcohols on the differentiation of neural stem cell derived neurospheres
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In a search for inducers of neuronal differentiation to treat neurodegenerative diseases such as Alzheimer's disease, a series of indole fatty alcohols (IFAs) were prepared, 13c (n = 18) was able to promote the differentiation of neural stem cell derived neurospheres into neurons at a concentration of 10 nM. Analysis of the expression of the Notch pathway genes in neurospheres treated during the differentiation phase with 13c (n = 18) revealed a significant decrease in the transcription of the Notch 4 receptor.
- Coowar, Djalil,Bouissac, Julien,Hanbali, Mazen,Paschaki, Marie,Mohier, Eliane,Luu, Bang
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p. 6270 - 6282
(2007/10/03)
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- Pyrrolo[2.1-a]isoquinoline derivatives
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The present invention relates to pyrrolo[2.1-a]isoquinolines which are inhibitors of phosphodiesterase 10a, a process for preparing these compounds and a method of treating cancer in humans and animals by administering these compounds.
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- Novel and potent human and rat β3-adrenergic receptor agonists containing substituted 3-indolylalkylamines
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A novel series of 2-(3-indolyl)alkylamino-1-(3-chlorophenyl)ethanols was prepared and evaluated for in vitro ability to stimulate cAMP production in Chinese hamster ovary cells expressing cloned human β3-AR. The optically active 30a was found to be the most potent and selective human β3-AR agonist in this series with an EC50 value of 0.062 nM. In addition, 30a selectivity for human β3-AR was 210-fold and 103-fold that for human β2-AR and β1-AR, respectively. Furthermore, 30a showed potent agonistic activity at rat β3-AR.
- Harada, Hiroshi,Hirokawa, Yoshimi,Suzuki, Kenji,Hiyama, Yoichi,Oue, Mayumi,Kawashima, Hitoshi,Yoshida, Naoyuki,Furutani, Yasuji,Kato, Shiro
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p. 1301 - 1305
(2007/10/03)
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- INDOLE DERIVATIVES HAVING A 2 PHENYL-ETHANOLAMINO-SUBSTITUTED LOWER ALKYL GROUP AT THE 2- OR 3- POSITION THEREOF
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An indole derivative of the formula: STR1 wherein R 1 is lower alkoxy, lower alkoxycarbonyl-lower alkoxy, carboxy-lower alkoxy, lower alkoxycarbonyl, phenyl-lower alkoxy, lower alkyl being optionally substituted by hydroxy, di-lower alkylaminosulfonyl, etc., R 2 is hydrogen, halogen, lower alkoxy, lower alkoxycarbonyl-lower alkoxy, carboxy-lower alkoxy, etc., R 3 is hydrogen or lower alkyl, R 4 is halogen or trifluoromethyl, R 5 is lower alkyl, or a salt thereof, these compounds being potent β 3-adrenergic receptor-stimulating agent with excellent adrenoceptor selectivity, and being useful in the prophylaxis or treatment of obesity or diabetes mellitus.
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- STRUCTURAL DETERMINATION OF A NATURAL ALKALOID, 5-METHOXY-1-OXO-1,2,3,4-TETRAHYDRO-β-CARBOLINE AND THE SYNTHESIS OF THE CORRESPONDING 8-METHOXY COMPOUND
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Structure of a natural alkaloid, 5-methoxy-1-oxo-1,2,3,4-tetrahydro-β-carboline, was determined unequivocally by synthesis and the reported spectral data were found to be revised in some points.
- Yamada, Fumio,Saida, Yoshihiro,Somei, Masanori
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p. 2619 - 2627
(2007/10/02)
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