550371-76-1Relevant articles and documents
Photoredox-catalysed regioselective synthesis of C-4-alkylated pyridines with N -(acyloxy)phthalimides
He, Qian,Yang, Chunhao,Zhang, Xiaofei,Zhang, Zhucheng
, p. 1969 - 1973 (2022/03/15)
A method of direct C-4 selective alkylation of pyridines under visible light irradiation at room temperature has been reported, using simple maleate-derived pyridinium salts as pyridine precursors and the readily available carboxylic acid-derived N-(acyloxy)phthalimides as alkyl radical precursors, affording good to excellent yields without using stoichiometric oxidants and acids. A broad range of primary, secondary, and tertiary carboxylates can be used as alkylation reagents. Oxidant and acid-sensitive functional groups can be tolerated well. This journal is
INHIBITORS OF THE NOTCH TRANSCRIPTIONAL ACTIVATION COMPLEX KINASE ("NACK") AND METHODS FOR USE OF THE SAME
-
Paragraph 00151, (2019/08/29)
Disclosed herein are Notch transcriptional activation complex kinase ("NACK") inhibitors, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein include compounds of Formula (la) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.
Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of replacement of the 3-hydroxyphenyl group with pyridine or thiophene bioisosteres
Kormos, Chad M.,Gichinga, Moses G.,Runyon, Scott P.,Thomas, James B.,Mascarella, S. Wayne,Decker, Ann M.,Navarro, Hernán A.,Carroll, F. Ivy
, p. 3842 - 3848 (2016/07/21)
The potent and selective KOR antagonist JDTic was derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid antagonists. In previous studies we reported that compounds that did not have a hydroxyl on the 3-hydroxyphenyl group and did not have methyl groups at the 3- and 4-position of the piperidine ring were still potent and selective KOR antagonists. In this study we report JDTic analogs 2, 3a–b, 4a–b, and 5, where the 3-hydroxyphenyl ring has been replaced by a 2-, 3-, or 4-pyridyl or 3-thienyl group and do not have the 3-methyl or 3,4-dimethyl groups, remain potent and selective KOR antagonists. Of these, (3R)-7-hydroxy-N-(1S)-2-methyl-[4-methyl-4-pyridine-3-yl-carboxamide (3b) had the best overall binding potency and selectivity in a [35S]GTPγS functional assay, with a Ke?=?0.18?nM at the KOR and 273- and 16,700-fold selectivity for the KOR relative to the MOR and DOR, respectively. Calculated physiochemical properties for 3b suggest that it will cross the blood–brain barrier.
DIARYL KETIMINE DERIVATIVE HAVING ANTAGONISM AGAINST MELANIN-CONCENTRATING HORMONE RECEPTOR
-
Page/Page column 34, (2010/12/31)
[Problems] To provide an antagonist of a melanin-concentrating hormone receptor, which is useful as a medicine for a central nervous system disease, a cardiovascular disease or a metabolic disease. [Means for Solving Problems] The antagonist comprises, as an active ingredient, a compound represented by the formula (I) wherein R1a and R1b independently represent a hydrogen atom or a C1-6 alkyl group; R2a, R2b, R3a and R3b independently represent a hydrogen atom, a C1-6 alkyl group, or the like; Y represents H or —OH; Z represents —OR8, or the like; R8 represents a hydrogen atom, a C1-6 alkyl group which may have a substituent, or the like; R9a and R9b independently represent a hydrogen atom, a C1-6 alkyl group, or the like; Ar1 represents an aromatic carbon ring group, or an aromatic heteroring group; Ar2 represents a group produced by removing two hydrogen atoms from an aromatic carbon ring, or the like; and the ring group A represents an unsaturated heteroring group.
DERIVATIVES OF UREAS OF PIPERIDINE OR PYRROLIDINE, THEIR PREPARATION AND THEIR THERAPEUTICAL USE
-
Page/Page column 27, (2009/07/18)
The present invention is related to a compound of formula (I): wherein i, j, n, o, p, q, r, R1a, R1b, R1c, R1d, R2a, R2b, R2c, R2d, R3a, R3b and R4 are as defined herein, or an addition salt with an acid thereof, or a hydrate or solvate thereof, its preparation, pharmaceutical composition, and uses for treating a disease in which the enzyme 11β-HSD1 is involved.
Wrenchnolol derivative optimized for gene activation in cells
Jung, Dongju,Shimogawa, Hiroki,Kwon, Youngjoo,Mao, Qian,Sato, Shin-ichi,et al.
supporting information; experimental part, p. 4774 - 4782 (2009/09/26)
Naturally occurring transcription factors usually have two independent domains, a DNA-binding domain and an activation domain. In designing a synthetic small molecule that mimics a transcription factor, each of the two domains needs to be replaced by small-molecule counterparts. Results of the present study show that derivatives of wrenchnolol, a synthetic molecule that interacts with Sur-2 coactivator, serve as activation modules and stimulate gene transcription in vitro and in cells when tethered to a DNA-binding molecule. Thirteen derivatives of wrenchnolol were chemically synthesized and tested for their ability to activate transcription in vitro and in cells. When tethered to the GAL4 DNA-binding domain, one derivative increased transcription of a GAL4-responsive reporter genein cells 9-fold. This optimized derivative also induced up to 45percent myogenesis of C2C12 cells when tethered to the DNA-binding domain of my ogenic transcription factor MyoD. This optimized derivative may serve asa starting point for designing biological tools or components of fully synthetic transcription factors that permit selective up-regulation of g enes.