552330-86-6Relevant articles and documents
INDOLE COMPOUNDS AS ANDROGEN RECEPTOR MODULATORS
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Page/Page column 40; 72, (2022/02/05)
Provided herein are compounds of formula (V) that bind to BF3 of an androgen receptor (AR), which can modulate the AR for the treatment of Kennedy's disease.
Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore
Daini, Masaki,Fujii, Takahiro,Ikeda, Zenichi,Inazuka, Masakazu,Kakegawa, Keiko,Kasahara, Takahito,Kikuchi, Fumiaki,Kimoto, Kouya,Kohara, Hiroshi,Mikami, Satoshi,Murakami, Masataka,Nakamura, Minoru,Oak, Jeong-Ho,Ohashi, Tomohiro,Oki, Hideyuki,Puenner, Florian,Sasaki, Minoru,Sato, Sho,Seto, Masaki,Suzaki, Tomohiko,Takai, Yuichi,Takami, Kazuaki,Tanaka, Yuta,Wada, Yasufumi,Wang, Junsi,Yamamoto, Takeshi
, p. 4270 - 4290 (2022/03/14)
Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher’s disease and has been suggested as a potential target for treating Parkinson’s disease. Herein, we report the discovery of novel brain-penetrant GCS inhibitors. Assessment of the structure-activity relationship revealed a unique pharmacophore in this series. The lipophilic ortho-substituent of aromatic ring A and the appropriate directionality of aromatic ring B were key for potency. Optimization of the absorption, distribution, metabolism, elimination, toxicity (ADMETox) profile resulted in the discovery of T-036, a potent GCS inhibitor in vivo. Pharmacophore-based scaffold hopping was performed to mitigate safety concerns associated with T-036. The ring opening of T-036 resulted in another potent GCS inhibitor with a lower toxicological risk, T-690, which reduced glucosylceramide in a dose-dependent manner in the plasma and cortex of mice. Finally, we discuss the structural aspects of the compounds that impart a unique inhibition mode and lower the cardiovascular risk.
Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase
Bagal, Sharan K.,Barton, Peter,Bloecher, Andrew,Borodovsky, Alexandra,Code, Erin,Fillery, Shaun M.,Gregson, Clare,Hsu, Jessie Hao-Ru,Kawatkar, Sameer P.,Li, Chengzhi,Longmire, David,Nai, Youfeng,Nash, Samuel C.,O' Donovan, Daniel H.,Pike, Andrew,Pike, Kurt G.,Rawlins, Phillip B.,Read, Jon A.,Robinson, James,Shen, Minhui,Tang, Jia,Wang, Peng,Williamson, Beth,Woods, Haley
, p. 17146 - 17183 (2021/12/06)
Aberrant activity of the histone methyltransferase polycomb repressive complex 2 (PRC2) has been linked to several cancers, with small-molecule inhibitors of the catalytic subunit of the PRC2 enhancer of zeste homologue 2 (EZH2) being recently approved fo
Br?nsted Acid Catalyzed Dearomatization by Intramolecular Hydroalkoxylation/Claisen Rearrangement: Diastereo- and Enantioselective Synthesis of Spirolactams
Chen, Peng-Fei,Wang, Binju,Wu, Peng,Ye, Long-Wu,Zhou, Bo
supporting information, p. 27164 - 27170 (2021/11/22)
Described herein is a novel Br?nsted acid catalyzed intramolecular hydroalkoxylation/Claisen rearrangement, allowing the practical and atom-economic synthesis of a range of valuable spirolactams from readily available ynamides in generally good to excellent yields with excellent diastereoselectivities and broad substrate scope. Importantly, an unexpected dearomatization of nonactivated arenes and heteroaromatic compounds is involved in this tandem sequence. Moreover, an asymmetric version of this tandem cyclization was also achieved by efficient kinetic resolution by chiral phosphoric acid catalysis. In addition, the [3,3]-rearrangement is shown to be kinetically preferred over the related [1,3]-rearrangement by theoretical calculations.
Degradable hydrogel under physiological conditions
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, (2020/09/09)
The present invention discloses a hydrogel that can be degraded under physiological conditions. The hydrogel includes at least one backbone moiety and an optional crosslinking moiety, and biodegradable linkers connecting backbone moieties and crosslinking moieties can be degraded by intramolecular cyclization.
BENZAZEPINE DERIVATIVE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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, (2019/03/29)
Disclosed are a benzazepine derivative, a preparation method, a pharmaceutical composition and the use thereof. A compound as shown in formula (I) of the present invention, and an isomer, a prodrug, a stable isotope derivative or a pharmaceutically acceptable salt thereof have the following structure. The benzazepine derivative of the present invention has a good regulation effect on the TLR family and the related signalling pathway, and in particular, has a good regulation effect on TLR8, can effectively treat, relieve and/or prevent various diseases mediated by TLR family and the TLR-related signalling pathway, and in particular, can effectively treat, relieve and/or prevent various diseases mediated by TLR8, such as cancers, autoimmune diseases, infections, inflammations, transplantation rejections, graft-versus-host diseases, etc.
Palladium-Catalyzed Direct C-H Carbonylation of Free Primary Benzylamines: A Synthesis of Benzolactams
Zhang, Chunhui,Ding, Yongzheng,Gao, Yuzhen,Li, Shangda,Li, Gang
supporting information, p. 2595 - 2598 (2018/05/22)
A protocol for palladium-catalyzed C-H carbonylation of readily available free primary benzylamines using NH2 as the chelating group under an atmospheric pressure of CO has been achieved, providing a general, atom- and step-economic approach to
Traceless Directing Group Assisted Cobalt-Catalyzed C?H Carbonylation of Benzylamines
Ling, Fei,Ai, Chongren,Lv, Yaping,Zhong, Weihui
supporting information, p. 3707 - 3712 (2017/10/07)
The first example of cobalt-catalyzed C(sp2)?H carbonylation of benzylamines using a traceless directing group is reported, which was successfully applied to the synthesis of N?unprotected iso-indolinones through direct C?H/N?H bonds activation. This protocol tolerates a variety of functional groups and provides a facile and efficient method for the formal synthesis of (+)-garenoxacin. (Figure presented.).
BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS
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, (2015/06/18)
Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.
NRF2 REGULATORS
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, (2015/07/07)
The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators.