- Modulation of the Antitumor Activity by Methyl Substitutions in the Series of 7H-Pyridocarbazole Monomers and Dimers
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The structure of the dimeric antitumor drug ditercalinium (NSC 366241) -1,1'-diyldi-2,1-ethanediyl)biscarbazolium>tetramethanesulfonate> was modified by introduction of methyl groups in various positions of the aromatic ring.Monomeric analogues with the nitrogen atom of the pyridinic ring in different positions have also been synthesized.Pharmacological properties and DNA interactions of the new compounds are reported.In contrast with the monomeric analogue of ditercalinium, which was inactive, methyl substitutions on the 10 methoxy-7H-pyridocarbazolium in positions 6 and 7 led to monomers endowed with small but significant activity.As expected, dimerization of the methyl-substituted pyridocarbazoles yielded DNA bisintercalators with affinity slightly higher than that of the unsubstituted parent compounds.These dimers, characterized by a relatively better therapeutic index, have the same mechanism of action as ditercalinium.Otherwise, in monomeric and dimeric series, methyl substitution in position 4 or 5 provided inactive compounds unable to intercalate into DNA.All these results are in agreement with the previously proposed geometry for the complex of ditercalinium with DNA.
- Leon, P.,Garbay-Jaureguiberry, C.,Barsi, M. C.,Pecq, J. B. Le,Roques, B. P.
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- Synthesis of Indole- and Pyrrole-Fused Seven-Membered Nitrogen Heterocycles via Acid-Base Switchable Cyclization Involving Cleavage of Amide C?N Bonds
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We report the method for synthesis of indole- and pyrrole-fused seven-membered nitrogen heterocycles by means of acid-base switchable cyclization reactions. The reactions involved cleavage of amide C?N bonds, chemoselective N-1 or C-3 acylation, and 1,4-M
- Hao, Yanke,Zhou, Pan,Niu, Kaikai,Song, Hongjian,Liu, Yuxiu,Zhang, Jingjing,Wang, Qingmin
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supporting information
p. 281 - 285
(2021/11/09)
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- Polycyclic compound for inhibiting DHX33 helicase
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The invention relates to a polycyclic compound for inhibiting DHX33 helicase. In particular, the invention relates to a compound shown as a formula I in the specification or a pharmaceutically acceptable form thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable form thereof, a preparation method of the compound or the pharmaceutically acceptable form thereof, and medical application of the compound or the pharmaceutically acceptable form thereof and the pharmaceutical composition to prevention and/or treatment of DHX33-related diseases.
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Paragraph 0255-0258
(2021/03/24)
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- Amide-Amine Replacement in Indole-2-carboxamides Yields Potent Mycobactericidal Agents with Improved Water Solubility
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Indolecarboxamides are potent but poorly soluble mycobactericidal agents. Here we found that modifying the incipient scaffold by amide-amine substitution and replacing the indole ring with benzothiophene or benzoselenophene led to striking (10-20-fold) im
- Tan, Yu Jia,Li, Ming,Gunawan, Gregory Adrian,Nyantakyi, Samuel Agyei,Dick, Thomas,Go, Mei-Lin,Lam, Yulin
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supporting information
p. 704 - 712
(2020/11/30)
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- Synthesis of Indole/Benzofuran-Containing Diarylmethanes through Palladium-Catalyzed Reaction of Indolylmethyl or Benzofuranylmethyl Acetates with Boronic Acids
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The palladium-catalyzed synthesis of indole/benzofurancontaining diarylmethanes starting from indolylmethyl or benzofuranylmethyl acetates with boronic acids has been investigated. The success of the reaction is influenced by the choice of precatalyst: with indolylmethyl acetates the reaction works well with [Pd(η3-C3H5)Cl]2/XPhos while with benzofuranylmethyl acetates Pd2(dba)3/XPhos is more efficient. The good to high yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2- and 3-substituted indoles and 2-benzo[b]furans. The methodology can be advantageously extended to the preparation of a key precursor of Zafirlukast.
- Arcadi, Antonio,Calcaterra, Andrea,Chiarini, Marco,Fabrizi, Giancarlo,Fochetti, Andrea,Goggiamani, Antonella,Iazzetti, Antonia,Marrone, Federico,Marsicano, Vincenzo,Serraiocco, Andrea
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supporting information
p. 741 - 753
(2021/11/26)
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- Carbene-Catalyzed Enantioselective Aromatic N-Nucleophilic Addition of Heteroarenes to Ketones
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The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi-functionalized cyclic N,O-acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza-fulvene-type acylazolium intermediate. A broad range of N-heteroaromatic aldehydes and electron-deficient ketone substrates works effectively in this transformation. Several of the chiral N,O-acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection.
- Liu, Yonggui,Luo, Guoyong,Yang, Xing,Jiang, Shichun,Xue, Wei,Chi, Yonggui Robin,Jin, Zhichao
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supporting information
p. 442 - 448
(2019/11/25)
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- Addition of a Carbene Catalyst to Indole Aryl Aldehyde Activates a Remote δ-sp2 Carbon for Protonation and Formal [4+2] Reaction
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The addition of a carbene catalyst to an indole aryl aldehyde leads to the activation of a remote sp2 carbon that is five atoms away from the catalyst. The unsaturated Breslow intermediate formed between the catalyst and substrate undergoes an internal redox reaction and remote carbon protonation to generate an analogous azolium vinyl enolate intermediate. Subsequent [4+2] reaction with cyclic imine substrates eventually affords multicyclic pyridoindoles as nearly single diastereomers with excellent enantioselectivities.
- Zheng, Pengcheng,Wu, Shuquan,Mou, Chengli,Xue, Wei,Jin, Zhichao,Chi, Yonggui Robin
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supporting information
p. 5026 - 5029
(2019/07/03)
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- Concise synthesis of carbazole-1,4-quinones and evaluation of their antiproliferative activity against HCT-116 and HL-60 cells
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We report a convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O2 atmosphere as an important step. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types.
- Nishiyama, Takashi,Hatae, Noriyuki,Yoshimura, Teruki,Takaki, Sawa,Abe, Takumi,Ishikura, Minoru,Hibino, Satoshi,Choshi, Tominari
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p. 561 - 577
(2016/07/06)
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- Facile Synthesis of 3-Halobenzo-heterocyclic-2-carbonyl Compounds via in situ Halogenation-Oxidation
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A facile method to synthesize 3-halobenzo-heterocyclic-2-carbonyl compounds is described. Mechanistic studies suggested that a halo-cyclization process, which generated the unstable spiro-acetal transition state and readily convertible to the corresponding carbonyl compound might be involved. Diverse 3-halobenzo-heterocyclic-2-carbonyl compounds could be synthesized with up to 95 % yield in mild conditions with inexpensive starting materials. (Figure presented.).
- Jiang, Xiaojian,Yang, Junjie,Zhang, Feng,Yu, Pei,Yi, Peng,Sun, Yewei,Wang, Yuqiang
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supporting information
p. 2678 - 2683
(2016/09/03)
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- Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity
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Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2-and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents.
- Trabbic, Christopher J.,Overmeyer, Jean H.,Alexander, Evan M.,Crissman, Emily J.,Kvale, Heather M.,Smith, Marcie A.,Erhardt, Paul W.,Maltese, William A.
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p. 2489 - 2512
(2015/03/30)
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- Generation of α-imino gold carbenes through gold-catalyzed intermolecular reaction of azides with ynamides
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The generation of α-imino gold carbenes via gold-catalyzed intermolecular reaction of azides and ynamides is disclosed. This new methodology allows for highly regioselective access to valuable 2-aminoindoles and 3-amino-β-carbolines in generally good to excellent yields. A mechanistic rationale for this tandem reaction, especially for the observed high regioselectivity, is supported by DFT calculations.
- Shu, Chao,Wang, Yong-Heng,Zhou, Bo,Li, Xin-Ling,Ping, Yi-Fan,Lu, Xin,Ye, Long-Wu
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supporting information
p. 9567 - 9570
(2015/08/18)
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- KAHA ligations that form aspartyl aldehyde residues as synthetic handles for protein modification and purification
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Aldehydes are widely recognized as valuable synthetic handles for the chemoselective manipulation of peptides and proteins. In this report, we show that peptides and small proteins containing the aspartic acid semialdehyde (Asa) side chain can be easily p
- Murar, Claudia E.,Thuaud, Frdric,Bode, Jeffrey W.
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supporting information
p. 18140 - 18148
(2015/03/04)
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- Rapid and selective access to three distinct sets of indole-based heterocycles from a single set of Ugi-adducts under microwave heating
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Three distinct sets of indole-based heterocycles were rapidly and selectively synthesized from the same set of Ugi-adducts under microwave heating in a reaction-condition-controlled manner. Notably, an unprecedented metal-free intramolecular sp3/sup
- Zhang, Lei,Zhao, Fei,Zheng, Mingyue,Zhai, Yun,Liu, Hong
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supporting information
p. 2894 - 2896
(2013/04/24)
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- Efficient and general synthesis of oxazino[4,3-a]indoles by cascade addition-cyclization reactions of (1H-indol-2-yl)methanols and vinyl sulfonium salts
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An efficient and general approach to oxazino[4,3-a]indole architectures is described. The addition-cyclization cascade of (1H-indol-2-yl)methanols with vinyl sulfonium salts affords oxazino[4,3-a]indole derivatives in high yields.
- An, Jing,Chang, Ning-Jie,Song, Li-Dong,Jin, Yu-Qin,Ma, Ying,Chen, Jia-Rong,Xiao, Wen-Jing
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supporting information; experimental part
p. 1869 - 1871
(2011/03/22)
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- Discovery of 4-amino and 4-hydroxy-1-aroylindoles as potent tubulin polymerization inhibitors
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1-Aroylindoline, 1-aroyl-1,2,3,4-tetrahydroquinoline, and 1-aroylindole derivatives were synthesized and evaluated for anticancer activity. The 4-amino and 4-hydroxy-1-aroylindoles 26 and 27 with IC50 of 0.9 and 0.6 μM, respectively, exhibited
- Liou, Jing-Ping,Wu, Zi-Yi,Kuo, Ching-Chuan,Chang, Chi-Yen,Lu, Pei-Yi,Chen, Chi-Ming,Hsieh, Hsing-Pang,Chang, Jang-Yang
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scheme or table
p. 4351 - 4355
(2009/05/26)
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- Design, synthesis, and melatoninergic activity of new azido- and isothiocyanato-substituted indoles
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To develop irreversibly binding ligands for the melatonin receptor(s) as tools for tracing the primary melatonin binding site, we report on the design and synthesis of new melatoninergic azido- and isothiocyanato-substituted indoles. All active compounds were partial agonists or antagonists in the Xenopus melanophore assay, the most potent being the 5-OMe C3-substituted azido 45 and isothiocyanato 46 analogues.
- Tsotinis, Andrew,Afroudakis, Pandelis A.,Davidson, Kathryn,Prashar, Anjali,Sugden, David
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p. 6436 - 6440
(2008/03/30)
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- 2-[N-acylamino(C1-C3)alkyl]indoles as MT1 melatonin receptor partial agonists, antagonists, and putative inverse agonists
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The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (8-11), acylaminoethyl (5a-k), or acylaminopropyl (13) side chains is reported. On the basis of a novel in vitro functional assay (specific bindin
- Spadoni, Gilberto,Balsamini, Cesarino,Bedini, Annalida,Diamantini, Giuseppe,Di Giacomo, Barbara,Tontini, Andrea,Tarzia, Giorgio,Mor, Marco,Plazzi, Pier Vincenzo,Rivara, Silvia,Nonno, Romolo,Pannacci, Marilou,Lucini, Valeria,Fraschini, Franco,Stankov, Bojidar Michaylov
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p. 3624 - 3634
(2007/10/03)
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- Method for the production of indolyl lactones
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A method for the production of indolyl lactones of the formula STR1 wherein R1 is hydrogen, halogen, or an alkoxy group having 1 to 4 C atoms and R3 is hydrogen, characterized in the manner that one reacts a 2-hydroxymethylindole of the formula STR2 wherein R1 has the above named meaning and R2 is an alkanoyl group or a phenyl alkanoyl group, with an α-diazoester of the formula STR3 wherein R3 has the above named meaning and R4 is an alkyl group having 1 to 4 C atoms and a, benzyl group, to a 3-indolyl acetic acid ester of the formula STR4 wherein R1, R2, R3 and R4 have the above named meanings, saponifies the thus obtained 3-indolyl acetic acid ester of the formula (IV) to the 3-indolyl acetic acid of the formula STR5 wherein R1 and R3 have the above named meaning, and the latter is dehydrated to indolyl lactone with the formula (I).
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