- Diazaphenoxazines and Diazaphenothiazines: Synthesis of the "correct" Isomers Reveals They Are Highly Reactive Radical-Trapping Antioxidants
-
The preparation of 2,4-diazaphenothiazines and 2,4-diazaphenoxazines via a copper-catalyzed intramolecular amination is described. Literature approaches which utilize easily accessed (2′-aminophenyl) 4-pyri(mi)dyl sulfides undergo a Smiles rearrangement that gives rise to the 1,3-diaza derivatives instead, confirmed by X-ray crystallography. Inversion of the polarity of the cyclization avoids the rearrangement and affords the desired products. Preliminary kinetic studies suggest that 2,4-diazaphenothiazines and diazaphenoxazines, but not the 1,3-diaza isomers, are remarkably potent radical-trapping antioxidants.
- Haidasz, Evan A.,Pratt, Derek A.
-
-
Read Online
- COMPOUNDS AND USES THEREOF
-
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
- -
-
Page/Page column 71; 120
(2021/08/06)
-
- HETEROCYCLIC GLP-1 AGONISTS
-
Provided are GLP-1 agonists of Formula (I) or (II), including pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions, and methods of using the same.
- -
-
Page/Page column 200-201
(2021/08/20)
-
- Cyclopalladation in the Periphery of a NHC Ligand as the Crucial Step in the Synthesis of Highly Active Suzuki–Miyaura Cross-Coupling Catalysts
-
Starting from 2,4-dichloropyrimidine, 4-(2-dialkylamino)pyrimidinyl functionalized mesitylimidazolium chlorides are accessible in a five-step reaction sequence. Two routes leading to palladium NHC complexes derived from these ligands have been worked out: By transmetalation with the corresponding NHC-AgCl complexes, C,N-coordinated palladium(II) complexes can be obtained. Treatment of palladium dichloride with the imidazolium salts in pyridine and in the presence of K2CO3 gives cyclometalated and thus C,C-coordinated compounds. The reactivities of all these compounds were investigated in detail as well as their performance in the catalytic Suzuki–Miyaura cross-coupling reaction. It turned out that the C,C-coordinated derivatives exhibit high catalytic activities in the coupling of arylboronic acids with aryl chlorides, which is consistent with the generally accepted mechanistic ideas on substrate activation.
- Fizia, Agnes,Gaffga, Maximilian,Lang, Johannes,Sun, Yu,Niedner-Schatteburg, Gereon,Thiel, Werner R.
-
supporting information
p. 14563 - 14575
(2017/10/07)
-
- Heat shock protein 70 inhibitors. 2. 2,5′-thiodipyrimidines, 5-(phenylthio)pyrimidines, 2-(pyridin-3-ylthio)pyrimidines, and 3-(phenylthio)pyridines as reversible binders to an allosteric site on heat shock protein 70
-
The discovery and development of heat shock protein 70 (Hsp70) inhibitors is currently a hot topic in cancer. In the preceding paper in this issue (10.1021/jm401551n), we have described structure-activity relationship studies in the first Hsp70 inhibitor class rationally designed to bind to a novel allosteric pocket located in the N-terminal domain of the protein. These ligands contained an acrylamide to take advantage of an active cysteine embedded in the allosteric pocket and acted as covalent protein modifiers upon binding. Here, we perform chemical modifications around the irreversible inhibitor scaffold to demonstrate that covalent modification is not a requirement for activity within this class of compounds. The study identifies derivative 27c, which mimics the biological effects of the irreversible inhibitors at comparable concentrations. Collectively, the back-to-back manuscripts describe the first pharmacophores that favorably and selectively interact with a never explored pocket in Hsp70 and provide a novel blueprint for a cancer-oriented development of Hsp70-directed ligands.
- Taldone, Tony,Kang, Yanlong,Patel, Hardik J.,Patel, Maulik R.,Patel, Pallav D.,Rodina, Anna,Patel, Yogita,Gozman, Alexander,Maharaj, Ronnie,Clement, Cristina C.,Lu, Alvin,Young, Jason C.,Chiosis, Gabriela
-
p. 1208 - 1224
(2014/03/21)
-
- HEAT SHOCK PROTEIN BINDING COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING AND USING SAME
-
The present subject matter relates to a compound represented by the general formula (I) or (I') or a pharmacologically acceptable salt thereof; pharmaceutical compositions containing at least one of these compounds; methods of making at least one of these compounds; methods of using at least one of these compounds for treating and/or preventing various cancers and/or proliferation disorders; methods of using at least one of these compounds for monitoring the effectiveness of an anticancer therapy against various cancers. In one embodiment, the subject matter relates to compounds that bind with a level of specificity to heat shock protein 70 (Hsp70). In another embodiment, the subject matter relates to compounds that bind with a level of specificity to inhibit both heat shock protein 70 (Hsp70) and heat shock cognate protein 70 (Hsc70).
- -
-
Page/Page column 169
(2011/04/13)
-
- PYRIMIDINE COMPOUNDS AS TUBERCULOSIS INHIBITORS
-
The present invention relates to compounds II useful as inhibitors of treating tuberculosis. The invention also provides processes for preparing compounds of the invention.
- -
-
Page/Page column 107
(2011/02/24)
-
- Bicyclic Kinase Inhibitors
-
New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.
- -
-
Page/Page column 28
(2011/08/22)
-
- METHOD AND INTERMEDIA USED TO OBTAIN DERIVATIVES OF 1-(1H- BENZIMIDAZOLE-2-YL)-4-(2-AMINOPYRIMIDINE)PIPERIDINE
-
The invention relates to a method of obtaining derivatives of 1-(1H-benzimidazole-2-il)-4-(2-aminopyrimidine)piperidine (IV), wherein - R1 represents hydrogen or 4-halobenzyl and R5 represents optionally-substituted hydrogen, alkyl or benzyl. The inventive method comprises the conversion of a 1-[1-(R1)-1H-benzimidazole-2-il]-4-(R2)(R3)-piperidine (I), wherein R2 or R3 represents optionally-protected hydroxy, or R2 and R3 represent, independently of each other, optionally-substituted alkoxy or benzyloxy, or R2 and R3 together form an optionally-substituted alkylenedioxy group, by means of hydrolysis and/or oxidation into a 1-[1-(R1)-1H-benzimidazole-2-il]-4-piperidone, which, by reductive amination (with optional separation of the intermediate imina formed) provides the corresponding amine which, by reaction with a pyrimidine, produces the above-mentioned derivative of 1-(1H-benzimidazole-2-il)-4-(2-aminopyrimidine) piperidine (IV).
- -
-
-
- Palladium-catalysed cross-coupling reactions of arylboronic acids with π-deficient heteroaryl chlorides
-
The palladium-catalysed cross-coupling reactions of arylboronic acids with a variety of π-deficient heteroaryl chlorides proceed in high yield. [1,4-Bis(diphenylphosphino)butane]palladium(II) dichloride was found to be a very satisfactory catalyst for monocyclic heteroaryl chlorides, whereas tetrakis(triphenylphosphine)palladium(O) was found to be excellent for a range of chloroquinoline derivatives.
- Ali,McKillop,Mitchell,Rebelo,Wallbank
-
p. 8117 - 8126
(2007/10/02)
-