65287-34-5Relevant academic research and scientific papers
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.
3-3 - diarylacrylate/amide compound containing triaryl phosphonium salt as well as preparation method and application thereof
-
Paragraph 0121, (2021/10/05)
The invention discloses I-3-diaryl acrylate/amide sterilization compounds of triarylphosphonium salts shown 3 . The compound of the formula I, which is an active ingredient, has a high activity in prevention and control of pathogenic bacteria in crops, horticulture, and vegetables, and can exhibit an excellent control effect even at a low dose, and has a wide control spectrum.
Amide compound as well as preparation method and application thereof
-
Paragraph 0218; 0223-0225, (2021/04/17)
The invention provides an amide compound as well as a preparation method and application thereof. The amide compound has a structure as shown in a formula I in the specification. The amide compound disclosed by the invention can have high insecticidal act
AMIDE COMPOUNDS AND PREPARATION METHOD THEREFOR AND USE THEREOF
-
Page/Page column 30, (2021/04/23)
Provided are amide compounds and a preparation method therefor and the use thereof. The amide compounds have a structure represented by formula (I). The amide compounds of the present invention have high insecticidal activity at a low dosage and have a go
Synthesis of N-trifluoromethyl amides from carboxylic acids
Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
supporting information, p. 2245 - 2255 (2021/08/12)
Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
FARNESOID X RECEPTOR AGONISTS AND USES THEREOF
-
Paragraph 00462, (2020/04/25)
Described herein are compounds that are farnesoid X receptor agonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.
CRBN LIGANDS AND USES THEREOF
-
Paragraph 00462-00464, (2019/08/20)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
TETRAHYDROISOQUINOLINE DERIVED PRMT5-INHIBITORS
-
Page/Page column 102, (2016/03/19)
A compound of formula I wherein: n is 1 or 2: p is 0 or 1; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl.
18F LABELLED THIAZOLYLHYDRAZONE DERIVATIVES
-
Page/Page column 10-11, (2016/07/05)
The present invention relates to compounds of Formula (I) wherein R1 and R2 are independently selected from 19F and 18F having selective binding for MAO-B as compared with MAO-A. The invention also provides radi
New anti-invasive compounds
-
Paragraph 0091, (2014/05/06)
The present invention relates to a compound of formula (I): wherein A and A' independently represent a phenylene group or a pyridylene group; R2 is a hydrogen atom or a (C1-C4)alkyl group; R3 is a 2-pyridyl grou
