Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones.

ABSTRACT: An oxidative reaction for the synthesis of 4-alkyl-substituted dihydroisoquinolin-1(2H)-ones with N-allylbenzamide derivatives as starting materials has been developed. The radical alkylarylation reaction proceeds through a sequence of alkylation and intramolecular cyclization. The substituent on the C-C double bond was found to play a key role for the progress of the reaction to give the expected products with good chemical yields. Additionally, N-methacryloylbenzamides were also suitable substrates for the current reaction and provided the alkyl-substituted isoquinoline-1,3(2H,4H)-diones in good yield.

SUBMITTER: Qian P

PROVIDER: S-EPMC4778529 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones.

Qian Ping P Du Bingnan B Jiao Wei W Mei Haibo H Han Jianlin J Pan Yi Y

Beilstein journal of organic chemistry 20160217

An oxidative reaction for the synthesis of 4-alkyl-substituted dihydroisoquinolin-1(2H)-ones with N-allylbenzamide derivatives as starting materials has been developed. The radical alkylarylation reaction proceeds through a sequence of alkylation and intramolecular cyclization. The substituent on the C-C double bond was found to play a key role for the progress of the reaction to give the expected products with good chemical yields. Additionally, N-methacryloylbenzamides were also suitable subst ...[more]

PMID: 26977189

Similar Datasets

4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors.

Project description:A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.

| S-EPMC4027527 | biostudies-literature

4-[(2,4-Dimethyl-1,3-oxazol-5-yl)meth-yl]-4-hydr-oxy-2-methyl-isoquinoline-1,3(2H,4H)-dione.

Project description:In the title isoquinolinedione derivative, C(16)H(16)N(2)O(4), the piperidine ring in the tetra-hydro-isoquinoline unit adopts a half-boat conformation. The essentially planar oxazole ring [maximum deviation = 0.004 (2) Å] is inclined at a dihedral angle of 36.00 (8)° to the tetra-hydro-isoquinoline unit. In the crystal structure, pairs of inter-molecular C-H⋯O and O-H⋯N inter-actions link the mol-ecules into chains incorporating R(2) (2)(9) ring motifs. Two neighbouring chains are further inter-connected by inter-molecular C-H⋯O inter-actions into chains two mol-ecules wide along the a axis.

| S-EPMC2983926 | biostudies-literature

4-[(2,5-Dimethyl-1,3-thia-zol-4-yl)meth-yl]-4-hydr-oxy-2-methyl-isoquinoline-1,3(2H,4H)-dione.

Project description:In the title isoquinoline-dione compound, C(16)H(16)N(2)O(3)S, the piperidine ring in the tetra-hydro-isoquinoline ring system adopts a half-boat conformation. The essentially planar thia-zole ring [maximum deviation = 0.007?(2)?Å] makes a dihedral angle of 34.49?(7)° with the mean plane through the tetra-hydro-isoquinoline ring system. In the crystal structure, two neighbouring mol-ecules are linked via pairs of O-H?N and C-H?O hydrogen bonds into inversion-related dimers incorporating R(2) (2)(9) hydrogen-bond ring motifs. These dimers are further linked by weak inter-molecular C-H?? inter-actions.

| S-EPMC2983771 | biostudies-literature

4-Benzylideneisoquinoline-1,3(<i>2H</i>,<i>4H</i>)-diones as tyrosyl DNA phosphodiesterase 2 (TDP2) inhibitors.

Project description:Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (Top2) mediated DNA damages, including double-strand breaks (DSBs) that underpin the anticancer mechanism of clinical TOP2 poisons such as etoposide (ETP). Inhibition of TDP2 could sensitize cancer cells toward TOP2 poisons by increasing Top2 cleavage complex. We have previously identified isoquinoline-1,3-dione as a selective inhibitor type of TDP2. However, the reported structure-activity relationship (SAR) was limited to simple substitutions on the isoquinoline-1,3-dione core. Herein, we report the extended SAR consisting of the synthesis and testing of a total of 50 analogs featuring N-2 and C-4 modifications. Major SAR observations include the loss of potency upon N-2 substitution, the lack of inhibition with C-4 enamine analogs (subtype 11), or any other C-4 modifications (subtypes 13-15) except for the benzylidene substitution (subtype 12), where eight analogs showed low micromolar potency. The best analog, 12q, inhibited TDP2 with an IC50 of 4.8 μM. Molecular modeling was performed to help understand the observed SAR trends. Overall, these SAR observations which could significantly benefit future work on the design of improved TDP2 inhibitors.

| S-EPMC7993140 | biostudies-literature

4-[(2,4-Dimethyl-thia-zol-5-yl)meth-yl]-4-hydr-oxy-2-methyl-isoquinoline-1,3(2H,4H)-dione.

Project description:In the title isoquinoline-dione derivative, C(16)H(16)N(2)O(3)S, the piperidine ring in the tetra-hydro-isoquinoline ring system adopts a distorted envelope conformation. The thia-zole ring is essentially planar [maximum deviation = 0.004?(1)?Å] and is inclined at a dihedral angle of 31.08?(3)° with respect to the mean plane through the tetra-hydro-isoquinoline ring system. In the crystal structure, inter-molecular O-H?O and C-H?O inter-actions link adjacent mol-ecules into a three-dimensional extended network. The crystal structure is further stabilized by weak C-H?? inter-actions.

| S-EPMC2984028 | biostudies-literature

4H-Benzo[d][1,3]oxazin-4-ones and Dihydro Analogs from Substituted Anthranilic Acids and Orthoesters.

Project description:A one-pot route to 2-alkyl and 2-aryl-4H-benzo[d][1,3]oxazin-4-ones (also known as 4H-3,1-benzoxazin-4-ones) has been developed and studied. The method involves the reaction of aryl-substituted anthranilic acids with orthoesters in ethanol catalyzed by acetic acid. Additionally, we have also investigated the reaction under microwave conditions. Not all of the substrates were successful in yielding the target heterocycles as some of the reactions failed to undergo the final elimination. This process led to the isolation of (±)-2-alkyl/aryl-2-ethoxy-1,2-dihydro-4H-benzo[d][1,3]oxazin-4-ones. The formation of the dihydro analogs correlated with the electron density on the aromatic ring: Electron-donating groups favored the 4H- benzo[d][1,3]oxazin-4-ones, while electron-withdrawing groups tended to favor the dihydro product. Substituting a pyridine ring for the benzene ring in the substrate acid suppressed the reaction.

| S-EPMC6804250 | biostudies-literature

Docking and antiherpetic activity of 2-aminobenzo[de]-isoquinoline-1,3-diones.

Project description:As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The new series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones was examined against HSV-1 and HSV-2 using a cytopathic effect inhibition assay. In terms of effective concentration (EC50), furaldehyde, thiophene aldehyde and allyl isothiocyanide derivatives 14?16 showed potent activity against HSV-1 (EC50 = 19.6, 16.2 and 17.8 ?g/mL), compared to acyclovir as a reference drug (EC50 = 1.8 ?g/mL). Moreover, 14 and 15 were found to exhibit valuable activity against HSV-2. Many of the tested compounds demonstrated weak to moderate EC50 values relative to their inactive parent compound (2-amino-1H-benzo[de]isoquinoline-1,3-dione), while compounds 7, 9, 13, 14, 15, 16, 21 and 22 were the most active set of antiviral compounds throughout this study. The cytotoxicity (CC50), EC50, and the selectivity index (SI) values were determined. In a molecular docking study, the ligand-receptor interactions of compounds 1-24 and their parent with the HSV-1 thymidine kinase active site were investigated using the Molegro Virtual Docker (MVD) software. Based on the potent anti-HSV properties of the previous naphthalimide condensate products, further exploration of this series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones is warranted.

| S-EPMC6272685 | biostudies-other

Isoquinoline-1,3-diones as Selective Inhibitors of Tyrosyl DNA Phosphodiesterase II (TDP2).

Project description:Tyrosyl DNA phosphodiesterase II (TDP2) is a recently discovered enzyme that specifically repairs DNA damages induced by topoisomerase II (Top2) poisons and causes resistance to these drugs. Inhibiting TDP2 is expected to enhance the efficacy of clinically important Top2-targeting anticancer drugs. However, TDP2 as a therapeutic target remains poorly understood. We report herein the discovery of isoquinoline-1,3-dione as a viable chemotype for selectively inhibiting TDP2. The initial hit compound 43 was identified by screening our in-house collection of synthetic compounds. Further structure-activity relationship (SAR) studies identified numerous analogues inhibiting TDP2 in low micromolar range without appreciable inhibition against the homologous TDP1 at the highest testing concentration (111 μM). The best compound 64 inhibited recombinant TDP2 with an IC50 of 1.9 μM. The discovery of this chemotype may provide a platform toward understanding TDP2 as a drug target.

| S-EPMC7832085 | biostudies-literature

An Efficient Synthesis of Bis-indolylindane-1,3-diones, Indan-1,3-diones, and Indene-1,3(2H)-denies Using [Hbim]BF 4 Ionic Medium.

Project description:We prepared a brand new molecule in one step for the synthesis of bis-indolylindane-1,3-dione and indan-1,3-diones from the reaction of ninhydrin and 3 substituted/unsubstituted indoles using [Hbim]BF4 ionic liquid in excellent yields. The method was also used for the synthesis of novel indene-1,3(2H)-denies derivatives.

| S-EPMC3876826 | biostudies-literature

Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones Derivatives.

Project description:Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel N-substituted 1H-pyrrolo[3-c]pyridine-1,3(2H)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC50 value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E-BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force.

| S-EPMC7355801 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data