79315-62-1Relevant articles and documents
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.
MAP4K4 (HGK) Inhibitors
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Paragraph 0277, (2016/08/10)
The invention provides mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibitors, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant diminution of tumor cell growth, cancer or metastasis.
NEW BICYCLIC DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Page/Page column 106-107, (2017/05/12)
Compounds of formula (I); wherein R1, R2, R3, R4, R5, R6, R7, R8, R14, W, A and n are as defined in the description. Medicaments.
The first potent inhibitor of mammalian group X secreted phospholipase A2: Elucidation of sites for enhanced binding
Smart, Brian P.,Oslund, Rob C.,Walsh, Laura A.,Gelb, Michael H.
, p. 2858 - 2860 (2007/10/03)
Using the X-ray structure of human group X secreted phospholipase A 2 (hGX), we carried out structure-based design of indole-based inhibitors and prepared the compounds using a new synthetic route. The most potent compound inhibited hGX and the mouse orthologue with an IC50 of 75 nM. This compound is the most potent hGX inhibitor reported to date and was also found to inhibit a subset of the other mouse and human SPLA 2S.
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).
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
