Search results for "Isoindole"

Structure‐Activity Relationships of Benzamides and Isoindolines Designed as SARS‐CoV Protease Inhibitors Effective against SARS‐CoV‐2

2020

Abstract Inhibition of coronavirus (CoV)‐encoded papain‐like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure‐activity relationships (SAR) of the noncovalent active‐site directed inhibitor (R)‐5‐amino‐2‐methyl‐N‐(1‐(naphthalen‐1‐yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS‐CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS‐CoV‐2 replication in …

(-)-(3a ' S,4 ' S,9b ' S,1R,2S,5R)-4 '-ethyl-3a ',4 ',5 ',7 ',8 ',9b '-hexahydro-2-isopropyl-5-methyl-2 '-phenylspiro[cyclo-hexane-1,7 '-dioxino[3,2-…

2005

The title compound, C27H33NO5, obtained from diethyl ether, crystallizes in space group P2(1) with four molecules in the asymmetric unit. The dioxinone and imide rings are almost planar, whereas the cyclohexane and cyclohexene rings form distorted conformations. The crystal structure confirms an earlier proposal about the stereoselectivity of Diels - Alder reactions to spirocyclic chiral 1,3- dienes.

Cryogenic 35GHz pulse ENDOR probehead accommodating large sample sizes: Performance and applications.

2009

The construction and performance of a cryogenic 35GHz pulse electron nuclear double resonance (ENDOR) probehead for large samples is presented. The resonator is based on a rectangular TE(102) cavity in which the radio frequency (rf) B(2)-field is generated by a two turn saddle ENDOR coil crossing the resonator along the sample axis with minimal distance to the sample tube. An rf power efficiency factor is used to define the B(2)-field strength per square-root of the transmitted rf power over the frequency range 2-180MHz. The distributions of the microwave B(1)- and E(1)-field, and the rf B(2)-field are investigated by electromagnetic field calculations. All dielectrics, the sample tube, and…

Local aromaticity mapping in the vicinity of planar and nonplanar molecules

2019

We report on nucleus-independent magnetic shielding (NICS) scans over the centers of six- and five-membered rings in selected metal phthalocyanines (MPc) and fullerene C60 for more accurate characterization of local aromaticity in these compounds. Detailed tests were conducted on model aromatic molecules including benzene, pyrrole, indole, isoindole, and carbazole and subsequently applied to H2 Pc, ZnPc, Al(OH)Pc, and CuPc. Similar behavior of three selected magnetic probes, Bq, 3 He, and 7 Li+ , approaching perpendicularly the ring centers, was observed. For better visualization of shielding zone over the centers of aromatic rings, we introduced a simple mathematical procedure: the first a…

ChemInform Abstract: Synthesis of Isoindolo[1,4]benzoxazinone and Isoindolo[1,5]benzoxazepine: Two New Ring Systems of Pharmaceutical Interest.

2016

Abstract Two new ring systems, isoindolo[1,4]benzoxazinone and isoindolo[1,5]benzoxazepine, were conveniently synthesized through cyclization of suitably substituted isoindole derivatives. Some of the new compounds exhibited antiproliferative activity against a wide range of human tumor cell lines with GI 50 mean values at low micromolar level (3.72–5.13 μM).

Gold-Catalyzed Intramolecular Hydroamination of o-Alkynylbenzyl Carbamates: A Route to Chiral Fluorinated Isoindoline and Isoquinoline Derivatives

2013

Enantiomerically pure fluorinated isoindoline and dihydroisoquinoline scaffolds have been prepared through a diastereoselective addition of fluorinated nucleophiles to Ellman’s N-(tert-butanesulfinyl)imines followed by a sequence of Sonogashira cross-coupling/gold(I)-catalyzed cycloisomerization of the corresponding carbamate. A more favored 5-exo-dig mechanism was observed mainly due to an electronic effect of the fluorinated group.

NUCLEOPHILIC SUBSTITUTIONS IN ISOINDOLE SERIES AS VALUABLE TOOL TO SYNTHESIZE DERIVATIVES WITH ANTITUMOR ACTIVITY

2009

ISOXAZOLO[5,4-E]ISOINDOLE: A NEW RING SYSTEM WITH POTETIAL PHOTOBIOLOGICAL PROPERTIES

2008

Convenient synthesis of pyrrolo[3,4-g]indazole

2013

Abstract The synthesis of a novel class of tetrahydropyrrolo[3,4-g]indazoles is reported, by annelation of the pyrazole ring on the isoindole moiety by means of 5-hydroxymethylene tetrahydroisoindole-4-ones key intermediates, with good regioselectivity. Dihydroderivatives were also obtained by oxidation with DDQ of the corresponding tetrahydropyrrolo[3,4-g]indazoles. The growth inhibitory effect was evaluated at the National Cancer Institute of Bethesda and some derivatives showed modest activity.

Harnessing medically relevant metals onto water-soluble subphthalocyanines: towards bimodal imaging and theranostics

2014

International audience; Subphthalocyanine (SubPc), a putative fluorophore for optical imaging (OI), was conjugated to chelating ligands (DOTA, DTPA) affording water-soluble conjugates complexed with (non-radioactive) metals relevant to the following medical imaging techniques/therapies: MRI (Gd), PET (Cu, Ga), SPECT (In, Ga, Lu), RIT (Cu, Lu, Y), and NCT (Gd). Magneto-optical properties of ditopic gadolinium species (and optical properties of other metal containing species) were examined (brightness (ε × Φ F) and relaxivity R 1) and fluorescence confocal/biphoton microscopy studies were conducted. † Electronic supplementary information (ESI) available: Experimental characterization, NMR and…