193217-39-9Relevant articles and documents
Synthesis and anticancer evaluation of 6-azacyclonol-2,4,6-trimethylpyridin-3-ol derivatives: M3 muscarinic acetylcholine receptor-mediated anticancer activity of a cyclohexyl derivative in androgen-refractory prostate cancer
Karmacharya, Ujjwala,Chaudhary, Prakash,Lim, Dongchul,Dahal, Sadan,Awasthi, Bhuwan Prasad,Park, Hee Dong,Kim, Jung-Ae,Jeong, Byeong-Seon
supporting information, (2021/03/16)
We recently reported 2,4,5-trimethylpyridin-3-ol with C(6)-azacyclonol, whose code name is BJ-1207, showing a promising anticancer activity by inhibiting NOX-derived ROS in A549 human lung cancer cells. The present study was focused on structural modification of the azacyclonol moiety of BJ-1207 to find a compound with better anticancer activity. Ten new compounds (3A–3J) were prepared and evaluated their inhibitory actions against proliferation of eighteen cancer cell lines as a primary screening. Among the ten derivatives of BJ-1207, the effects of compounds 3A and 3J on DU145 and PC-3, androgen-refractory cancer cell lines (ARPC), were greater than the parent compound, and compound 3A showed better activity than 3J. Antitumor activity of compound 3A was also observed in DU145-xenografted chorioallantoic membrane (CAM) tumor model. In addition, the ligand-based target prediction and molecular docking study using DeepZema server showed compound 3A was a ligand to M3 muscarinic acetylcholine receptor (M3R) which is overexpressed in ARPC. Carbachol, a muscarinic receptor agonist, concentration dependently increased proliferation of DU145 in the absence of serum, and it also activated NADPH oxidase (NOX). The carbachol-induced proliferation and NOX activity was significantly blocked by compounds 3A in a concentration-dependent manner. This finding might become a new milestone in the development of pyridinol-based anti-cancer agents against ARPC.
OXIME COMPOUNDS USEFUL AS T CELL ACTIVATORS
-
, (2022/01/04)
Disclosed herein are oxime compounds having the structure of Formula (I):or a pharmaceutically acceptable salt, solvate, hydrate, isomer, tautomer, racemate, or isotope thereof, wherein R1, R2, R3, a, L, X, and Y are as defined herein. Pharmaceutical compositions comprising them, processes for preparing them and uses of them to treat or prevent diseases, disorders and conditions are also provided. The compounds are inhibitors of one or both of diacylglycerol kinase alpha (DGKα) and diacylglycerol kinase zeta (DGKζ) and are useful in the treatment of diseases, disorders and conditions related to DGKα and / or DGKζ activity. In particular, the compounds are useful for treating viral infections and proliferative disorders, such as cancer.
NOVEL ARYLOXYPIPERIDINE PYRAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS
-
Page/Page column 92; 93, (2020/03/15)
Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
Nickel-Catalyzed Suzuki-Miyaura Coupling of Aliphatic Amides
Boit, Timothy B.,Weires, Nicholas A.,Kim, Junyong,Garg, Neil K.
, p. 1003 - 1008 (2018/02/14)
We report the Ni-catalyzed Suzuki-Miyaura coupling of aliphatic amide derivatives. Prior studies have shown that aliphatic amide derivatives can undergo Ni-catalyzed carbon-heteroatom bond formation but that Ni-mediated C-C bond formation using aliphatic amide derivatives has remained difficult. The coupling disclosed herein is tolerant of considerable variation with respect to both the amide-based substrate and the boronate coupling partner and proceeds in the presence of heterocycles and epimerizable stereocenters. Moreover, a gram-scale Suzuki-Miyaura coupling/Fischer indolization sequence demonstrates the ease with which unique polyheterocyclic scaffolds can be constructed, particularly by taking advantage of the enolizable ketone functionality present in the cross-coupled product. The methodology provides an efficient means to form C-C bonds from aliphatic amide derivatives using nonprecious-metal catalysis and offers a general platform for the heteroarylation of aliphatic acyl electrophiles.
ISOXAZOLE CARBOXAMIDE COMPOUNDS
-
Paragraph 0273, (2016/06/01)
The present disclosure provides substituted isoxazole carboxamide compounds having Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, A, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.
PIPERIDINE AMIDE DERIVATIVES AS HIV ATTACHMENT INHIBITORS
-
Page/Page column 63; 64, (2014/03/21)
Compounds of Formula I, including pharmaceutically acceptable salts thereof: formule (I): wherein A is selected from the group consisting of:formule (II) and wherein Z is selected from the group consisting of: formule (III):,, and. are useful as HIV attac
Iodonium ylides for one-step, no-carrier-added radiofluorination of electron rich arenes, exemplified with 4-(([18F]fluorophenoxy)- phenylmethyl)piperidine NET and SERT ligands
Cardinale, Jens,Ermert, Johannes,Humpert, Sven,Coenen, Heinz H.
, p. 17293 - 17299 (2014/05/06)
Iodonium ylide precursors of electron rich arenes, i.e. the NET and SERT ligands 4-((3- and 4-fluorophenoxy)phenylmethyl)piperidine, served as model compounds for the direct substitution with n.c.a. [18F]fluoride. Good radiochemical yields of a
Preparation of unsymmetrical ketones from tosylhydrazones and aromatic aldehydes via formyl C-H bond insertion
Allwood, Daniel M.,Blakemore, David C.,Ley, Steven V.
, p. 3064 - 3067 (2014/06/23)
Preparation of ketones by insertion of diazo compounds into the formyl C-H bond of an aldehyde is an attractive procedure, but use of structurally diverse diazo compounds is hampered by preparation and safety issues. A convenient procedure for the synthesis of unsymmetrical ketones from bench-stable tosylhydrazones and aryl aldehydes is reported. The procedure can be performed in one pot from the parent carbonyl compound and needs only a base, with no additional promoters being required.
Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres
Sheffler, Douglas J.,Nedelovych, Michael T.,Williams, Richard,Turner, Stephen C.,Duerk, Brittany B.,Robbins, Megan R.,Jadhav, Sataya B.,Niswender, Colleen M.,Jones, Carrie K.,Conn, P. Jeffrey,Daniels, R. Nathan,Lindsley, Craig W.
, p. 1062 - 1066 (2014/03/21)
This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores.
Ketone formation via mild Nickel-catalyzed reductive coupling of alkyl halides with aryl acid chlorides
Wu, Fan,Lu, Wenbin,Qian, Qun,Ren, Qinghua,Gong, Hegui
supporting information; experimental part, p. 3044 - 3047 (2012/08/07)
The present work highlights unprecedented Ni-catalyzed reductive coupling of unactivated alkyl iodides with aryl acid chlorides to efficiently generate alkyl aryl ketones under mild conditions.
