- A Paramagnetic NMR Spectroscopy Toolbox for the Characterisation of Paramagnetic/Spin-Crossover Coordination Complexes and Metal–Organic Cages
-
The large paramagnetic shifts and short relaxation times resulting from the presence of a paramagnetic centre complicate NMR data acquisition and interpretation in solution. As a result, NMR analysis of paramagnetic complexes is limited in comparison to diamagnetic compounds and often relies on theoretical models. We report a toolbox of 1D (1H, proton-coupled 13C, selective 1H-decoupling 13C, steady-state NOE) and 2D (COSY, NOESY, HMQC) paramagnetic NMR methods that enables unprecedented structural characterisation and in some cases, provides more structural information than would be observable for a diamagnetic analogue. We demonstrate the toolbox's broad versatility for fields from coordination chemistry and spin-crossover complexes to supramolecular chemistry through the characterisation of CoII and high-spin FeII mononuclear complexes as well as a Co4L6 cage.
- Lehr, Marc,McConnell, Anna J.,N?ther, Christian,Paschelke, Tobias,S?nnichsen, Frank D.,Trumpf, Eicke,Vogt, Anna-Marlene
-
supporting information
p. 19344 - 19351
(2020/09/01)
-
- The development of improved syntheses of PPARγ-sparing, insulin sensitizing thiazolidinedione-ketones
-
Ketones 2 (MSDC-0160) and 3 (MSDC-0602) had been selected for clinical development, however their initial syntheses were considered suboptimal for application deep into clinical trials. Difficulties ranging from the nature of the starting material, alcohol oxidation problems, epoxide opening regioisomeric issues, and endgame ketone redox problems had been encountered. Direct ketone introduction/maintenance was desired for maximum efficiency and convergence was found to be critically dependent upon the acidity of the nucleophilic species (13, 18) and the use of pre- or post-alkylative oximino-ether/oxime protection (vide infra). Improvements in overall yield for the syntheses of 2 (MSDC-0160) and 3 (MSDC-0602) from 20% (2) and 31% (3) respectively, to 44% (2) and 59% (3) were realized.
- Tanis, Steven P.,Colca, Jerry R.,Parker, Timothy T.,Artman, Gerald D.,Larsen, Scott D.,Gadwood, Robert C.,Zeller, James R.
-
supporting information
(2019/07/30)
-
- Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
-
Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
-
p. 5852 - 5869
(2018/11/10)
-
- DYE, AND PHOTOELECTRIC CONVERSION ELEMENT AND PHOTOELECTROCHEMICAL CELL USING THE SAME
-
PROBLEM TO BE SOLVED: To provide a photoelectric conversion element and photoelectrochemical cell that achieves a high photoelectric conversion efficiency and in addition that has excellent durability, as well as to provide a dye used therein. SOLUTION: Provided is a dye represented by formula: MLt2L1. (M is ruthenium, osmium, iron, rhenium or technetium; Lt2 is a tridentate ligand represented by the formula (2-2); and L1 is a tridentate ligand of bis-pyrazole-substituted pyridine compound.). (R1 and R2 is -COOH or the like, La is a single bond or an arylene group; n1 is an integer of 1 to 3; n2 is an integer of 1 to 4; R6 is a substituent containing a C1 to 30 alkyl group or the like; and n6 is an integer of 1 to 5.). SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0111; 0112
(2016/10/08)
-
- Triply Threaded [4]Rotaxanes
-
[4]Rotaxanes featuring three axles threaded through a single ring have been prepared through active metal template synthesis. Nickel-catalyzed sp3-sp3 homocouplings of alkyl bromide "half-threads" through 37- and 38-membered 2,2′:6′,2″-terpyridyl macrocycles generate triply threaded [4]rotaxanes in up to 11% yield. An analogous 39-membered macrocycle produced no rotaxane products under similar conditions. The constitutions of the [4]rotaxanes were determined by NMR spectroscopy and mass spectrometry. Doubly threaded [3]rotaxanes were also obtained from the reactions but no [2]rotaxanes were isolated, suggesting that upon demetalation the axle of a singly threaded rotaxane can slip through a macrocycle that is sufficiently large to accommodate three threads.
- Danon, Jonathan J.,Leigh, David A.,McGonigal, Paul R.,Ward, John W.,Wu, Jhenyi
-
supporting information
p. 12643 - 12647
(2016/10/07)
-
- Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones
-
As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu2+/Zn2+, while others were effective at inhibiting the action of AChE.
- Fosso, Marina Y.,LeVine, Harry,Green, Keith D.,Tsodikov, Oleg V.,Garneau-Tsodikova, Sylvie
-
supporting information
p. 9418 - 9426
(2015/09/15)
-
- IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR
-
Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-KB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.
- -
-
Page/Page column 78
(2015/03/13)
-
- USE OF PYRAZOLOPYRIMIDINE DERIVATIVES FOR THE TREATMENT OF PI3K-DELTA RELATED DISORDERS
-
The present application provides methods of treating PI3Kδ related disorders using compounds of Formula I: or pharmaceutically acceptable salts thereof.
- -
-
Paragraph 0512
(2014/09/16)
-
- ACETYLENIC MICROBIOCIDES
-
Compounds of formula (I), wherein the other substituents HetAr, A', R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined in claim 1, and their use in compositions and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
- -
-
Page/Page column 36-37
(2013/10/21)
-
- CONDENSED TRICLYCLIC COMPOUNDS AS INHIBITORS OF HIV REPLICATION
-
Compounds of formula (I) and pharmaceutical compositions thereof: wherein A1 A2 and A3 are each independently selected from the group consisting of N and CR3, wherein R1 is an optionally substituted heterocyclyl or an optionally substituted -(C1-6)alkyl-heterocyclyl, R2 is an optionally substituted aryl or an optionally subsisted heteroaryl, R4 is an optionally substituted aryl, an optionally substituted heterocyclyl or an optionally substituted heteroaryl, useful as an inbitor of HIV replication.
- -
-
Page/Page column 78-79
(2013/07/05)
-
- SYNTHESIS FOR THIAZOLIDINEDIONE COMPOUNDS
-
The present invention provides novel methods for synthesizing PPARgamma sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.
- -
-
Page/Page column 32
(2012/03/09)
-
- Facile synthesis and platinum complexes of 4′,5,5′′- trisubstituted-2,2′:6′,2′′-terpyridines
-
The synthesis of trisubstituted 4′,5,5′′ terpyridines is described. The strategy begins with synthesis of 2-acetyl-5-bromopyridine (3) from 2,5-dibromopyridine, substitution of the bromine in 3 using a variety of metal-catalyzed reactions and then formation of the terpyridine using the Krohnke reaction. The complexes have been prepared by reaction of [Pt(PhCN) 2Cl2] with the appropriate silver salt followed by addition of the terpyridyl ligand. The crystal structure of two complexes have been determined via X-ray diffraction and the MLCT (metal-to-ligand charge-transfer) emissions determined by UV/Vis spectroscopy. The Royal Society of Chemistry 2011.
- Huo, Jianqiang,Arulsamy, Navamoney,Hoberg, John O.
-
scheme or table
p. 7534 - 7540
(2011/10/12)
-
- Theramutein modulators
-
This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.
- -
-
Page/Page column 202
(2010/02/17)
-
- ANTIMICROBIAL HETEROCYCLIC COMPOUNDS FOR TREATMENT OF BACTERIAL INFECTIONS
-
The present invention provides heterocyclic compounds of the following formula (I) : or pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof useful as antibacterial agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
- -
-
Page/Page column 67
(2008/12/08)
-
- THERAMUTEIN MODULATORS
-
This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.
- -
-
Page/Page column 239
(2008/12/07)
-
- Triazolopyridines. Part 26: The preparation of novel [1,2,3]triazolo[1,5-a]pyridine sulfoxides
-
The regioselective synthesis of new triazolopyridine halides and sulfoxides with the substituent in all different ring positions of [1,2,3]triazolo[1,5-a]pyridines is presented. The triazolo ring opening reaction of some representative sulfoxides to obtain disubstituted pyridines is also studied.
- Abarca, Belén,Ballesteros, Rafael,Ballesteros-Garrido, Rafael,Colobert, Fran?oise,Leroux, Frédéric R.
-
p. 3794 - 3801
(2008/09/20)
-
- Novel substituted (pyridin-3-yl)phenyloxazolidinones: Antibacterial agents with reduced activity against monoamine oxidase A and increased solubility
-
Oxazolidinones represent a new and promising class of antibacterial agents. Current research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Oxazolidinones bearing a (pyridin-3-yl)phenyl moiety (e.g., 3) generally show improved antibacterial activity compared to linezolid but suffer from potent monoamine oxidase A (MAO-A) inhibition and low solubility. We now disclose the finding that new analogues of 3 with acyclic substituents on the pyridyl moiety exhibit excellent activity against Gram-positive pathogens, including linezolid-resistant Streptococcus pneumoniae. Generally, more bulky substituents yielded significantly reduced MAO-A inhibition relative to the unsubstituted compound 3. The MAO-A SAR can be rationalized on the basis of docking studies using a MAO-A/MAO-B homology model. Solubility was enhanced with incorporation of polar groups. One optimized analogue, compound 13, showed low clearance in the rat and efficacy against S. pneumoniae in a mouse pneumonia model.
- Reck, Folkert,Zhou, Fei,Eyermann, Charles J.,Kern, Gunther,Carcanague, Dan,Ioannidis, Georgine,Illingworth, Ruth,Poon, Grace,Gravestock, Michael B.
-
p. 4868 - 4881
(2008/03/12)
-
- 5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d] pyrimidin-4-ylamine: Structure-activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors
-
4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay).
- Matulenko, Mark A.,Lee, Chih-Hung,Jiang, Meiqun,Frey, Robin R.,Cowart, Marlon D.,Bayburt, Erol K.,DiDomenico Jr., Stanley,Gfesser, Gregory A.,Gomtsyan, Arthur,Guo, Zhu Zheng,McKie, Jeffery A.,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,Alexander, Karen M.,McGaraughty, Steve,Wismer, Carol T.,Mikusa, Joseph,Marsh, Kennan C.,Snyder, Ronald D.,Diehl, Marilyn S.,Kowaluk, Elizabeth A.,Jarvis, Michael F.,Bhagwat, Shripad S.
-
p. 3705 - 3720
(2007/10/03)
-
- 3- `4- {6-SUBSTITUTED ALKANOYL) PYRIDIN-3-YL} -3-PHENYL! -5- (1H-1, 2, 3-TRIAZOL-1-YLMETHYL) -1, 3-OXAZOLIDIN-2-ONES AS ANTIBACTERIAL AGENTS
-
Compounds of formula (I) as well as pharmaceutically-acceptable salts and pro-drugs thereof are disclosed wherein R1, R2, R3, and R4 are defined herein. Also disclosed are processes for making compounds of formula (I) as well as methods of using compounds of formula (I) for treating bacterial infections.
- -
-
Page/Page column 44
(2010/02/15)
-
- 3- {4- (PYRIDIN-3-YL) PHENYL} -5- (1H-1, 2, 3-TRIAZOL-1-YLMETHYL) -1, 3-OXAZOLIDIN-2-ONES AS ANTIBACTERIAL AGENTS
-
Compounds of formula (I), as well as pharmaceutically-acceptable salts and pro-drugs thereof, are disclosed wherein R1, R2, R3, and R4 are defined herein. Also disclosed are processes for making compounds of formula (I) as well as methods of using compounds of formula (I) for treating bacterial infections.
- -
-
Page/Page column 44-45
(2010/02/15)
-
- Synthesis and antibacterial activity of oxazolidinones containing pyridine substituted with heteroaromatic ring
-
Oxazolidinone derivatives containing pyridine substituted with heteroaromatic ring were synthesized and exhibited potent in vitro and in vivo antibacterial activities against many antibiotic-resistant microbial strains. A series of oxazolidinone derivatives, which morpholino group of linezolid was replaced with heteroaromatic ring substituted pyridine moiety, were newly synthesized, and their substituted effects on in vitro and in vivo antibacterial activities were evaluated against four problematic gram-positive strains including drug resistant strains and two gram-negative strains. Most compounds exhibited the enhanced in vitro activities with 4-16-fold and three compounds exerted more than 2-fold increased in vivo efficacies than linezolid.
- Jo, Yeong Woo,Im, Weon Bin,Rhee, Jae Keol,Shim, Mi Ja,Kim, Won Bae,Choi, Eung Chil
-
p. 5909 - 5915
(2007/10/03)
-