One‐Pot Tandem Palladium‐Catalyzed Decarboxylative Cross‐Coupling and CH Activation Route to Thienoisoquinolines

Chen, Fei; Wong, Nicholas; Forgione, Pat

doi:10.1002/adsc.201300924

Cited by 17 publications

(9 citation statements)

References 59 publications

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“…The scope of the reaction was examined on different aromatic sulfonamides containing electron donating groups as well as electron withdrawing groups (Scheme 144). [148] They have also demonstrated a one pot synthesis of C-5 substituted thieno[3,2-c]isoquinoline 251 using palladium catalyzed reaction conditions (Scheme 145).…”

Section: Pd-catalyzed Isoquinoline Synthesismentioning

confidence: 99%

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Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

2020

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In the past decades, an enormous number of reports have been dedicated towards the synthesis of nitrogen containing heterocycles. This immense interest have emerged owing to their wide varieties of pharmacological activities. The present review focused on the synthesis of isoquinoline derivatives, a family of N-heterocycles showing a broad range of structural diversity, biological and pharmaceutical activities. The progress on their synthetic strategies using versatile approaches are discussed in details.

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Section: Pd-catalyzed Isoquinoline Synthesismentioning

confidence: 99%

“…The scope of the reaction was examined on different aromatic sulfonamides containing electron donating groups as well as electron withdrawing groups (Scheme 144). [148] …”

Section: Synthesis Of Isoquinoline Derivativesmentioning

confidence: 99%

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

2020

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“…We strategically designed the compounds to have properties ideal for in vivo use and screened derivatives for their ability to block cancer cell proliferation. The compounds share a core scaffold amenable to modifications 43 . We identified several derivatives that caused toxicity and mitotic arrest with IC 50 values in the sub micromolar range 44 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells

Jaunky

Larocque

Husser

et al. 2021

Sci Rep

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We reveal the effects of a new microtubule-destabilizing compound in human cells. C75 has a core thienoisoquinoline scaffold with several functional groups amenable to modification. Previously we found that sub micromolar concentrations of C75 caused cytotoxicity. We also found that C75 inhibited microtubule polymerization and competed with colchicine for tubulin-binding in vitro. However, here we found that the two compounds synergized suggesting differences in their mechanism of action. Indeed, live imaging revealed that C75 causes different spindle phenotypes compared to colchicine. Spindles remained bipolar and collapsed after colchicine treatment, while C75 caused bipolar spindles to become multipolar. Importantly, microtubules rapidly disappeared after C75-treatment, but then grew back unevenly and from multiple poles. The C75 spindle phenotype is reminiscent of phenotypes caused by depletion of ch-TOG, a microtubule polymerase, suggesting that C75 blocks microtubule polymerization in metaphase cells. C75 also caused an increase in the number of spindle poles in paclitaxel-treated cells, and combining low amounts of C75 and paclitaxel caused greater regression of multicellular tumour spheroids compared to each compound on their own. These findings warrant further exploration of C75’s anti-cancer potential.

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“…Our approach was to strategically design and synthesize a family of compounds with properties ideal for in vivo use and screen derivatives for their ability to arrest cancer cell proliferation. The compounds share a common core thienoisoquinoline scaffold amenable to modifications via structure-activity-relationship (SAR) studies (Chen et al 2014). We identified several derivatives that cause mitotic arrest with an IC50 for viability in the nanomolar range.…”

Section: Introductionmentioning

confidence: 99%

A novel compound that disrupts mitotic spindle poles in human cells

Jaunky

Husser

Larocque

et al. 2020

Preprint

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We characterize the mechanism of action of a new microtubule-targeting compound in cells. Microtubule-targeting drugs are used as successful anti-cancer therapies. We synthesized a family of compounds that share a common scaffold and have several functional groups amenable to modifications. We found that one of the active derivatives, C75, reduces cell viability and prevents microtubule polymerization in vitro. In this study, we explore the phenotypes caused by C75 in cells. It causes mitotic arrest and spindle phenotypes in several cancer cell lines in the nanomolar range. C75 can bind to the Colchicine-pocket on tubulin in vitro, but causes different effects on microtubules in cells. While Colchicine causes a decrease in microtubules and spindle pole collapse without re-growth, similar concentrations of C75 cause a rapid loss of microtubules and spindle pole fragmentation followed by microtubule re-growth to form multipolar spindles. In addition, C75 and Colchicine synergize for reduced viability and spindle phenotypes. Importantly, the phenotypes caused by C75 are similar to those caused by the depletion of ch-TOG, a microtubule polymerase, and tubulin and ch-TOG are displaced and oscillate in C75-treated cells. This suggests that C75 causes microtubule depolymerization in cells either directly or indirectly via inhibiting ch-TOG. This unique effect of C75 on microtubules warrants further exploration of its anti-cancer potential.

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One‐Pot Tandem Palladium‐Catalyzed Decarboxylative Cross‐Coupling and CH Activation Route to Thienoisoquinolines

Cited by 17 publications

References 59 publications

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells

A novel compound that disrupts mitotic spindle poles in human cells

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