Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-amino-9-deoxydaunomycin and related compounds

Ishizumi, Kikuo; Ohashi, Naohito; Tanno, Norihiko

doi:10.1021/jo00229a010

Cited by 85 publications

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“…The chemical structure and acute toxicity of amrubicin are similar to those of doxorubicin (6,7); however, it shows almost no cardiotoxicity (8,9). Amrubicin alone and combination chemotherapy with cisplatin exhibited high response rates of 75.8% and 87.8% and median survival times of 11.7 and 13.6 months in previously untreated ED-SCLC, respectively (10,11).…”

Section: Introductionmentioning

confidence: 96%

A phase II study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer

Ikeda

Fukuda

Nakamura

et al. 2014

Cancer Chemother Pharmacol

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Section: Introductionmentioning

confidence: 96%

A phase II study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer

Ikeda

Fukuda

Nakamura

et al. 2014

Cancer Chemother Pharmacol

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“…1) Doxorubicin hydrochloride was purchased from Kyowa Hakko Co. (Tokyo). The chemical structures of amrubicin, amrubicinol, and doxorubicin are shown in Ref.…”

Section: Chemicalsmentioning

confidence: 99%

Tumor‐selective Distribution of an Active Metabolite of the 9‐Aminoanthracycline Amrubicin

Noguchi¹,

Ichii²,

Morisada³

et al. 1998

Japanese Journal of Cancer Research

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It has been reported that the 9-aminoanthracycline amrubicin shows good efficacy in human tumor xenograft models. We studied the disposition and metabolism of amrubicin in mice, in comparison with those of doxorubicin. Amrubicinol, a 13-hydroxy metabolite of amrubicin, which is 10 to 100 times more cytotoxic than amrubicin, was detected as a major metabolite in blood and tissues, and aglycones of amrubicin were also detected. A pharmacokinetic study revealed that amrubicin had a smaller distribution volume and a shorter half-life than doxorubicin. In several normal tissues, the levels of amrubicin and amrubicinol were lower than those of doxorubicin. In contrast, the tumor levels of amrubicinol in the mice treated with amrubicin were higher than those of doxorubicin in the mice treated with that drug, in tumors that are sensitive to amrubicin. These results suggest that the potent therapeutic activity of amrubicin is caused by the selective distribution of its highly active metabolite, amrubicinol, in tumors.

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“…Amrubicin is a synthetic 9-aminoanthracycline that is converted to its active metabolite, amrubicinol, through the reduction of its C-13 ketone group to a hydroxy group (6). Amrubicin and amrubicinol are topoisomerase II inhibitors, which have been demonstrated to exert antitumor activities in various human tumor xenograft models (7).…”

Section: Introductionmentioning

confidence: 99%

Correlation between the efficacy of amrubicin and the previous chemotherapy regimen for relapsed small cell lung cancer

et al. 2017

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Abstract. Amrubicin has been demonstrated to be beneficial in the treatment of patients with relapsed small cell lung cancer (SCLC). The aim of the present study was to evaluate whether there is a significant difference in the efficacy of amrubicin between patients with relapsed SCLC who were previously treated with a platinum agent in combination with a topoisomerase I inhibitor, and those patients previously treated with a platinum agent in combination with a topoisomerase II inhibitor. The medical records of patients with SCLC, who were diagnosed as having relapsed following treatment with a platinum-based regimen and subsequently received amrubicin monotherapy, were retrospectively reviewed. Of a total of 48 patients with SCLC who were treated with amrubicin, the overall response rate, median progression-free survival (PFS) time and median survival time (MST) were determined to be 31.3%, 7.1 and 17.0 months, respectively. The response rate, PFS time and MST did not differ significantly between the patients treated previously with a platinum agent in combination with irinotecan, a topoisomerase I inhibitor, (36.4%, 5.7 and 11.4 months, respectively) and those treated previously with a platinum agent in combination with etoposide, a topoisomerase II inhibitor (30.0%, 4.7 and 14.8 months, respectively). The results indicate that amrubicin may be effective as a second-line chemotherapeutic agent for patients with SCLC, irrespective of which platinum agent and topoisomerase inhibitor-based chemotherapy regimen was previously administered. IntroductionSmall-cell lung cancer (SCLC) is the most aggressive type of lung cancer and has a poor prognosis (1). The standard therapy for extensive SCLC is chemotherapy with a platinum compound (carboplatin or cisplatin) administered in combination with etoposide, a topoisomerase II inhibitor (2). A Japanese phase III study [Japan Clinical Oncology Group (JCOG) 9511] investigated the clinical outcomes patients who were administered cisplatin and etoposide, compared with those who received cisplatin and irinotecan, a topoisomerase I inhibitor (3). Irrespective of the regimen selected, the majority of patients experience relapse or disease progression following an initial response to chemotherapy, and second-line therapy is subsequently required (4,5).Amrubicin is a synthetic 9-aminoanthracycline that is converted to its active metabolite, amrubicinol, through the reduction of its C-13 ketone group to a hydroxy group (6). Amrubicin and amrubicinol are topoisomerase II inhibitors, which have been demonstrated to exert antitumor activities in various human tumor xenograft models (7). The drug has been evaluated in a number of Japanese studies and reported to yield a response rate of 36-52% and a median survival time of 7-12 months when administered as a second-line treatment (8-13). The results of previous studies have indicated that amrubicin is useful for the treatment of relapsed SCLC (8-13).Few previous studies have evaluated the efficacy of amrubicin as a second-line treatmen...

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Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-amino-9-deoxydaunomycin and related compounds

Cited by 85 publications

References 0 publications

A phase II study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer

A phase II study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer

Tumor‐selective Distribution of an Active Metabolite of the 9‐Aminoanthracycline Amrubicin

Correlation between the efficacy of amrubicin and the previous chemotherapy regimen for relapsed small cell lung cancer

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