First Total Synthesis of (Z)-11-(2-oxopropylidene)-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5(10H)-one

More, Satish S.; Shanmughapriya, D.; Lingam, Y.; Patel, Navin B.

doi:10.1080/00397910802638537

Cited by 16 publications

(8 citation statements)

References 13 publications

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“…Reduction of the nitro group was followed by diazotization in the presence of sodium azide to obtain the desired bait 3 . 13,14 Gratifyingly, 3 retained potent anti-EboV activity (IC50 < 0.5 μM) and was not cytotoxic.…”

mentioning

confidence: 97%

Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

Lee

Ren

Côté

et al. 2012

ACS Med. Chem. Lett.

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A high throughput screen identified adamantane dipeptide 1 as an inhibitor of Ebola virus (EboV) infection. Hit-to-lead optimization to determine the structure-activity relationship (SAR) identified the more potent EboV inhibitor 2 and a photoaffinity labeling agent 3. These anti-viral compounds were employed to identify the target as Niemann-Pick C1 (NPC1), a host protein that binds the EboV glycoprotein and is essential for infection. These studies establish NPC1 as a promising target for anti-viral therapy.

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mentioning

confidence: 97%

Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

Lee

Ren

Côté

et al. 2012

ACS Med. Chem. Lett.

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“…An optically pure fuligocandin A ( 1 ) was synthesized by More et al. in 2009, using the aza‐Wittig method . A practical racemic first total synthesis of fuligocandin B ( 2 ) was achieved by Bergman and co‐workers in 2010, using Eschenmoser episulfide contraction as the key step.…”

Section: Resultsmentioning

confidence: 99%

Valosin‐containing Protein is a Target of 5′‐l Fuligocandin B and Enhances TRAIL Resistance in Cancer Cells

et al. 2016

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Fuligocandin B (2) is a novel natural product that can overcome TRAIL resistance. We synthesized enatiomerically pure fuligocandin B (2) and its derivative 5′‐I fuligocandin B (4), and found that the latter had an improved biological activity against the human gastric cancer cell line, AGS. We attached a biotin linker and photoactivatable aryl diazirine group to 5′‐I fuligocandin B (4), and employed a pull‐down assay to identify valosin‐containing protein (VCP/p97), an AAA ATPase, as a 5′‐I fuligocandin B (4) target protein. Knock‐down of VCP by siRNA enhanced sensitivity to TRAIL in AGS cells. In addition, 4 enhanced CHOP and DR5 protein expression, and overall intracellular levels of ubiquitinated protein. These data suggest that endoplasmic reticulum stress caused through VCP inhibition by 4 increases CHOP‐mediated DR5 up‐regulation, which enhances TRAIL‐induced cell death in AGS cells. To the best of our knowledge, this is the first example to show a relationship between VCP and TRAIL‐resistance‐overcoming activity in cancer cells.

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“…In 2009, during the course of our own investigations, More et al reported on the first synthesis of fuligocandin A, which was prepared in 6 steps. 81 Diazotization of anthranilic acid (84) followed by treatment with sodium azide afforded the azide derivative 85 which upon subsequent amidation gave compound 86. Activation of compound 86 with ethyl chloroformate followed by homologation with diazomethane gave α-diazo ketone 87 which could be isolated as both syn and anti rotamers (5.2:1) (Scheme 2.2).…”

Section: More's Approachmentioning

confidence: 99%

“…This is in agreement with the observations of Arai et al and also More et al, who reported that racemization readily occurs at this center under basic or acidic conditions (See 2.3.2.). [81][82]…”

Section: Preparation Of Fuligocandin Amentioning

confidence: 99%

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

2009

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Addition of organometallics to N-(alpha-haloacyl)-o-aminobenzonitrile resulted in the formation of 2,5-disubstituted 1,4-benzodiazepin-3-ones, whereas N-(beta-haloacyl)-o-aminobenzonitrile gave 2,6-disubstituted 1,5-benzodiazocin-4-ones under similar conditions. Initial cylization of N-(beta-haloacyl)-o-aminobenzonitrile to obtain the corresponding lactam (e.g.alpha,alpha-dimethyl-N-(2-cyanophenyl)-beta-lactam) increased the yield of 1,5-benzodiazocin-4-ones significantly. Somewhat surprisingly, addition of lithium reagents to N-(beta-haloacyl)-o-aminobenzonitrile gave 4,4-disubstituted quinazolines via Grob fragmentation.

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First Total Synthesis of (Z)-11-(2-oxopropylidene)-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5(10H)-one

Cited by 16 publications

References 13 publications

Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

Valosin‐containing Protein is a Target of 5′‐l Fuligocandin B and Enhances TRAIL Resistance in Cancer Cells

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

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