Serendipitous Discovery of a Prodrug of a <scp>PARP</scp>‐1 Inhibitor

Dunn, Derek; Husten, Jean; Aimone, Lisa D.; Ator, Mark A.; Chatterjee, Sankar

doi:10.1111/cbdd.12165

Cited by 6 publications

(1 citation statement)

References 11 publications

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“…Chemical reduction of this compound was shown, but no further testing for efficacy was reported. More recently, another hypoxia-activated PARP inhibitor, an imide-N protected pyrrolocarbazole CEP-9722, was reported (99). Pharmacokinetic studies revealed that the protected compound was converted to the active molecule in plasma in rats.…”

Section: Molecularly Targeted Bioreductive Prodrugsmentioning

confidence: 99%

Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy

Mistry

Thomas

Calder

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

115

117

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With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is hypoxia-activated prodrugs (HAPs), also known as bioreductive prodrugs. These prodrugs are inactive in cells with normal oxygen levels but in hypoxic cells (with low oxygen levels) undergo chemical reduction to the active compound. Hypoxia is a common feature of solid tumors and is associated with a more aggressive phenotype and resistance to all modes of therapy. Therefore, the combination of radiation therapy and bioreductive drugs presents an attractive opportunity for synergistic effects, because the HAP targets the radiation-resistant hypoxic cells. Hypoxia-activated prodrugs have typically been precursors of DNA-damaging agents, but a new generation of molecularly targeted HAPs is emerging. By targeting proteins associated with tumorigenesis and survival, these compounds may result in greater selectivity over healthy tissue. We review the clinical progress of HAPs as adjuncts to radiation therapy and conclude that the use of HAPs alongside radiation is vastly underexplored at the clinical level.

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Section: Molecularly Targeted Bioreductive Prodrugsmentioning

confidence: 99%

Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy

Mistry

Thomas

Calder

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

115

117

View full text Add to dashboard Cite

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Ruthenium(II)‐Catalyzed CH Activation with Isocyanates: A Versatile Route to Phthalimides

Sarkar

Ackermann

2014

Chemistry A European J

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A cationic ruthenium(II)-complex was utilized in the efficient synthesis of phthalimide derivatives by C-H activation with synthetically useful amides. The reaction proceeded through a mechanistically unique insertion of a cycloruthenated species into a C-Het multiple bond of isocyanate. The novel method also proved applicable for the synthesis of heteroaromatic unsymmetric diamides as well as a potent COX-2 enzyme inhibitor.

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Phthalimide-N-sulfonic acid, an efficient catalyst for the synthesis of various isoindoline-1,3-dione derivatives

Habibi

Pordanjani

2017

Chem. Pap.

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Serendipitous Discovery of a Prodrug of a PARP‐1 Inhibitor

Abstract: During SAR development of previously reported pyrrolocarbazole 1, a potent PARP-1 inhibitor, compound 14, was discovered serendipitously to be a prodrug of compound 1.

Cited by 6 publications

References 11 publications

Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy

Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy

Ruthenium(II)‐Catalyzed CH Activation with Isocyanates: A Versatile Route to Phthalimides

Phthalimide-N-sulfonic acid, an efficient catalyst for the synthesis of various isoindoline-1,3-dione derivatives

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