5443-16-3Relevant articles and documents
Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells
Camara, Ramatoulie,Ogbeni, Deborah,Gerstmann, Lisa,Ostovar, Mehrnoosh,Hurer, Ellie,Scott, Mark,Mahmoud, Nasir G.,Radon, Tomasz,Crnogorac-Jurcevic, Tatjana,Patel, Pryank,Mackenzie, Louise S.,Chau, David Y.S.,Kirton, Stewart B.,Rossiter, Sharon
, (2020/07/23)
S100P, a calcium-binding protein, is known to advance tumor progression and metastasis in pancreatic and several other cancers. Herein is described the in silico identification of a putative binding pocket of S100P to identify, synthesize and evaluate novel small molecules with the potential to selectively bind S100P and inhibit its activation of cell survival and metastatic pathways. The virtual screening of a drug-like database against the S100P model led to the identification of over 100 clusters of diverse scaffolds. A representative test set identified a number of structurally unrelated hits that inhibit S100P-RAGE interaction, measured by ELISA, and reduce in vitro cell invasion selectively in S100P-expressing pancreatic cancer cells at 10 μM. This study establishes a proof of concept in the potential for rational design of small molecule S100P inhibitors for drug candidate development.
Polycyclic Maleimide-based Scaffold as New Privileged Structure for Navigating the Cannabinoid System Opportunities
Bisi, Alessandra,Mokhtar Mahmoud, Alì,Allará, Marco,Naldi, Marina,Belluti, Federica,Gobbi, Silvia,Ligresti, Alessia,Rampa, Angela
supporting information, p. 596 - 600 (2019/04/25)
The discovery of the relevant role played by a dysregulation of the endogenous cannabinoid system in several pathological conditions has prompted an extensive research in this field. In this Letter, a series of cannabinoid receptor ligands bearing a previously unexplored polycyclic scaffold was designed and synthesized, in order to evaluate the potential of a new easily affordable privileged structure. The new compounds showed an appreciable affinity and a significant selectivity for the CB2 receptor and are endowed with an intriguing noncompetitive antagonist behavior. Due to the ability of the polycyclic structure to be easily modified in different ways, these compounds could represent convenient chemical tools to be exploited in order to better understand the endocannabinoid system impact on physiopathological conditions.
Electrostatically Driven CO-πAromatic Interactions
Li, Ping,Vik, Erik C.,Maier, Josef M.,Karki, Ishwor,Strickland, Sharon M. S.,Umana, Jessica M.,Smith, Mark D.,Pellechia, Perry J.,Shimizu, Ken D.
supporting information, p. 12513 - 12517 (2019/09/04)
A series of N-arylimide molecular balances were developed to study and measure carbonyl-aromatic (CO-π) interactions. Carbonyl oxygens were observed to form repulsive interactions with unsubstituted arenes and attractive interactions with electron-deficient arenes with multiple electron-withdrawing groups. The repulsive and attractive CO-πaromatic interactions were well-correlated to electrostatic parameters, which allowed accurate predictions of the interaction energies based on the electrostatic potentials of the carbonyl and arene surfaces. Due to the pronounced electrostatic polarization of the C=O bond, the CO-πaromatic interaction was stronger than the previously studied oxygen-πand halogen-πaromatic interactions.
Design and synthesis of c3-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence
Kotha, Sambasivarao,Todeti, Saidulu,Aswar, Vikas R.
, p. 2537 - 2544 (2018/10/21)
We have developed an efficient synthetic strategy to assemble C3-symmetric molecules containing propellane moieties as end groups and a benzene ring as a central core. The synthesis of these C3-symmetric molecules involves simple starting materials. Our approach to C3-symmetric compounds relies on a Diels–Alder reaction, cyclotrimerization and ring-closing metathesis as key steps.
Synthesis of propellanes containing a bicyclo[2.2.2]octene unit: Via the Diels-Alder reaction and ring-closing metathesis as key steps
Kotha, Sambasivarao,Pulletikurti, Sunil
, p. 14906 - 14915 (2018/04/30)
The synthesis of propellanes containing bicyclo[2.2.2]octene via olefin metathesis approach is less explored. Herein, we describe a simple and convenient method to synthesize propellane derivatives containing a bicyclo[2.2.2]octene unit which are structurally similar to 11β-HSD1 inhibitors by sequential usage of the Diels-Alder reaction, C-allylation and ring-closing metathesis (RCM) as the key steps. Additionally, we expanded this approach to an endo-tricyclo[4.2.2.02,5]decene derivative which is a useful monomer for polymer synthesis and we have also synthesized basketene and anthracene-based propellanes using the same strategy.
Iron-Catalyzed Ring-Closing C?O/C?O Metathesis of Aliphatic Ethers
Biberger, Tobias,Makai, Szabolcs,Lian, Zhong,Morandi, Bill
supporting information, p. 6940 - 6944 (2018/05/14)
Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring-closing reactions. Herein, we report an iron-catalyzed ring-closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.
Rational design of novel TLR4 ligands by in silico screening and their functional and structural characterization in vitro
Honegr, Jan,Malinak, David,Dolezal, Rafael,Soukup, Ondrej,Benkova, Marketa,Hroch, Lukas,Benek, Ondrej,Janockova, Jana,Kuca, Kamil,Prymula, Roman
, p. 38 - 46 (2018/02/15)
The purpose of this study was to identify new small molecules that possess activity on human toll-like receptor 4 associated with the myeloid differentiation protein 2 (hTLR4/MD2). Following current rational drug design principles, we firstly performed a ligand and structure based virtual screening of more than 130 000 compounds to discover until now unknown class of hTLR4/MD2 modulators that could be used as novel type of immunologic adjuvants. The core of the in silico study was molecular docking of flexible ligands in a partially flexible hTLR4/MD2 receptor model using a peta-flops-scale supercomputer. The most promising substances resulting from this study, related to anthracene-succimide hybrids, were synthesized and tested. The best prepared candidate exhibited 80% of Monophosphoryl Lipid A in vitro agonistic activity in cell lines expressing hTLR4/MD2.
ANTHRACENE BASED COMPOUNDS AND THEIR USES
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Page/Page column 26, (2016/12/01)
The present invention relates to compounds of the general formula (A) and their applicability for use in the treatment or prophylaxis of a disease, in particular for use as in treatment of cancer, in particular for use as in treatment of pancreatic cancer, in particular as inhibitors of S100P/RAGE interaction in pancreatic cancer. In summary herein are presented a group of compounds for use as in treatment of cancer, in particular as inhibitors of S100P/RAGE interaction in pancreatic cancer. The compounds have general formula (A): (A) or may be a pharmaceutically acceptable salt, solvate, hydrate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, stereoisomer or mixture thereof. X is independently NO2 or H; and Y is independently H or a side group. The compounds all have a lower fused ring system based on nitroanthracene or anthracene. The group Y attached to the N of the succinimide group varies between the compounds. For example, Y may be substituted or non-substituted benzene ring. Alternatively, in some examples Y is a heteroaromatic system. It has been discovered from studies by the inventors that the compounds described will inhibit S100P/RAGE interaction and are therefore useful for treating pancreatic cancer.
Decorating the Edges of a 2D Polymer with a Fluorescence Label
Zhao, Yingjie,Bernitzky, Richard H. M.,Kory, Max J.,Hofer, Gregor,Hofkens, Johan,Schlüter, A. Dieter
supporting information, p. 8976 - 8981 (2016/07/30)
This work proves the existence and chemical addressability of defined edge groups of a 2D polymer. Pseudohexagonally prismatic single crystals consisting of layered stacks of a 2D polymer are used. They should expose anthracene-based edge groups at the six (100) but not at the two pseudohexagonal (001) and (001) faces. The crystals are reacted with the isotopically enriched dienophiles maleic anhydride and a C18-alkyl chain-modified maleimide. In both cases the corresponding Diels-Alder adducts between these reagents and the edge groups are formed as confirmed by solid state NMR spectroscopy. The same applies to a maleimide derivative carrying a BODIPY dye which was chosen for its fluorescence to be out of the range of the self-fluorescence of the 2D polymer crystals stemming from contained template molecules. If the crystals are excited at λ = 633 nm, their (100) faces and thus their rims fluoresce brightly, while the pseudohexagonal faces remain silent. This is visible when the crystals lie on a pseudohexagonal face. Lambda-mode laser scanning microscopy confirms this fluorescence to originate from the BODIPY dye. Micromechanical exfoliation of the dye-modified crystals results in thinner sheet packages which still exhibit BODIPY fluorescence right at the rim of these packages. This work establishes the chemical nature of the edge groups of a 2D polymer and is also the first implementation of an edge group modification similar to end group modifications of linear polymers.
Design and Performance Validation of a Conductively Heated Sealed-Vessel Reactor for Organic Synthesis
Obermayer, David,Znidar, Desiree,Glotz, Gabriel,Stadler, Alexander,Dallinger, Doris,Oliver Kappe
, p. 11788 - 11801 (2016/12/09)
A newly designed robust and safe laboratory scale reactor for syntheses under sealed-vessel conditions at 250 °C maximum temperature and 20 bar maximum pressure is presented. The reactor employs conductive heating of a sealed glass vessel via a stainless steel heating jacket and implements both online temperature and pressure monitoring in addition to magnetic stirring. Reactions are performed in 10 mL borosilicate vials that are sealed with a silicone cap and Teflon septum and allow syntheses to be performed on a 2-6 mL scale. This conductively heated reactor is compared to a standard single-mode sealed-vessel microwave instrument with respect to heating and cooling performance, stirring efficiency, and temperature and pressure control. Importantly, comparison of the reaction outcome for a number of different synthetic transformations performed side by side in the new device and a standard microwave reactor suggest that results obtained using microwave conditions can be readily mimicked in the operationally much simpler and smaller conventionally heated device.
