95969-13-4Relevant academic research and scientific papers
Discovery of 1-(phenylsulfonyl)-1H-indole-based multifunctional ligands targeting cholinesterases and 5-HT6 receptor with anti-aggregation properties against amyloid-beta and tau
Wichur, Tomasz,Pasieka, Anna,Godyń, Justyna,Panek, Dawid,Góral, Izabella,Latacz, Gniewomir,Honkisz-Orzechowska, Ewelina,Bucki, Adam,Siwek, Agata,G?uch-Lutwin, Monika,Knez, Damijan,Brazzolotto, Xavier,Gobec, Stanislav,Ko?aczkowski, Marcin,Sabate, Raimon,Malawska, Barbara,Wi?ckowska, Anna
, (2021/08/30)
Multifunctional ligands as an essential variant of polypharmacology are promising candidates for the treatment of multi-factorial diseases like Alzheimer's disease. Based on clinical evidence and following the paradigm of multifunctional ligands we have r
Development and crystallography-aided SAR studies of multifunctional BuChE inhibitors and 5-HT6R antagonists with β-amyloid anti-aggregation properties
Brazzolotto, Xavier,Bucki, Adam,Gobec, Stanislav,Knez, Damijan,Latacz, Gniewomir,Malawska, Barbara,Mordyl, Barbara,Siwek, Agata,Walczak, Maria,Wichur, Tomasz,?niecikowska, Joanna,Góral, Izabella,G?uch-Lutwin, Monika,Godyń, Justyna,Juki?, Marko,Ko?aczkowski, Marcin,Sa?at, Kinga,Wi?ckowska, Anna
, (2021/09/15)
The lack of an effective treatment makes Alzheimer's disease a serious healthcare problem and a challenge for medicinal chemists. Herein we report interdisciplinary research on novel multifunctional ligands targeting proteins and processes involved in the development of the disease: BuChE, 5-HT6 receptors and β-amyloid aggregation. Structure-activity relationship analyses supported by crystallography and docking studies led to the identification of a fused-type multifunctional ligand 50, with remarkable and balanced potencies against BuChE (IC50 = 90 nM) and 5-HT6R (Ki = 4.8 nM), and inhibitory activity against Aβ aggregation (53% at 10 μM). In in vitro ADME-Tox and in vivo pharmacokinetic studies compound 50 showed good stability in the mouse liver microsomes, favourable safety profile and brain permeability with the brain to plasma ratio of 6.79 after p.o. administration in mice, thus being a promising candidate for in vivo pharmacology studies and a solid foundation for further research on effective anti-AD therapies.
New, concise route to indoles bearing oxygen or sulfur substituent at the 4-position. Synthesis of (±)- and (S)-(-)-pindolol and (±)-chuangxinmycin
Ishibashi,Akamatsu,Iriyama,Hanaoka,Tabata,Ikeda
, p. 271 - 276 (2007/10/02)
A new method for the synthesis of 4-alkoxy- and 4-[alkyl (or aryl)thio]indoles has been developed by using the indolone 3 as a common intermediate. The indolone 3 was prepared from N-(phenylsulfonyl)pyrrole (7) and the α-chlorosulfide 8 in four steps. Heating of a mixture of 3 and an appropriate alcohol in the presence of p-toluenesulfonic acid and cupric chloride afforded the 4-alkoxyindoles 11a-d. The method was applied to the synthesis of (±)-pindolol (19) and (S)-(-)-pindolol (20). Thiols also reacted with 3 in the presence of boron trifluoride to give 4-[aryl (or alkyl)thio]indoles 12, 21a, b, and 22a-d. The (indol-4-ylthio)acetate 22c was employed as a key intermediate for a concise total synthesis of (±)- chuangxinmycin (27).
A new, general entry to 4-substituted indoles. Synthesis of (S)-(-)-pindolol and (±)-chuangxinmycin
Ishibashi, Hiroyuki,Tabata, Takashi,Hanaoka, Kyoko,Iriyama, Hiroko,Akamatsu, Susumu,Ikeda, Masazumi
, p. 489 - 492 (2007/10/02)
A new method for synthesis of 4-substituted indoles has been developed by using the 7-arylthio-6-7-dihydroindol-4(5H) one 5 as a common intermediate. The method was applied to the synthesis of (S)-(-)-pindolol (11) and (±)-chuangxinmycin (16).
Preparation of alkyl-substituted indoles in the benzene portion. Part 6. Synthetic procedure for 4-, 5-, 6-, or 7-alkoxy-and hydroxyindole derivatives
Fuji,Muratake,Natsume
, p. 2344 - 2352 (2007/10/02)
A novel method for the preparation of indole derivatives that are alkoxy- and hydroxy-substituted in the benzene portion of the indole nucleus is described. The acid-induced cyclization reaction of (arylsulfonyl)pyrrole derivatives (4a, 4b, 5b, and 5a) in
Selective halogenation of 4-oxo-4,5,6,7-tetrahydroindoles to 5-halo-4-oxo-4,5,6,7-tetrahydroindoles with copper(II) halides
Matsumoto, Masakatsu,Ishida, Yasuko,Watanabe, Nobuko
, p. 165 - 170 (2007/10/02)
Halogenation of 4-oxo-4,5,6,7-tetrahydroindoles with copper(II) bromide or copper(II) chloride gave selectively 5-halo-4-oxo-4,5,6,7-tetrahydroindoles, which were easily transformed to 4-hydroxyindoles by the action of lithium halide/lithium carbonate in
