Synthesis and Biological Activity of 5'-Aminobenzoxazinorifamycin Derivatives.

Yamane, Tsutomu; Hashizume, Takuji; Yamashita, Katsuji; Hosoe, Kazunori; Hidaka, T; Watanabe, Kiyoshi; Kawaharada, Hajime; Kudoh, S

doi:10.1248/cpb.40.2707

Cited by 4 publications

(2 citation statements)

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“…Recent developments in the chemical derivatization of the rifamycin scaffold have afforded benzoxazinorifamycins,15 a subclass of rifamycins with unrivalled potency, generally orders of magnitude more potent than other rifamycins in vitro. In particular, rifalazil ( 3 ) is under clinical development for the treatment of chlamydial infections 16.…”

Section: Methodsmentioning

confidence: 99%

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Bisphosphonated Benzoxazinorifamycin Prodrugs for the Prevention and Treatment of Osteomyelitis

et al. 2008

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Benzoxazinorifamycins are potent antibacterial agents currently in development. Tethering these antibiotics to a bisphosphonate functional group by a cleavable linker allows the delivery of these agents to osseous tissues, where they can be released over time to treat bone infections. Various linker strategies are presented herein to develop osteotropic prodrugs, the activities of which are examined in vitro and in vivo.

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Section: Methodsmentioning

confidence: 99%

“…Benzoxazinorifamycins 2 a – c were prepared as reported by the treatment of the silylated precursor 1 and a secondary amine under oxidative conditions (Scheme ) 15. Compound 2 c can be readily converted into rifalazil ( 3 ) by reductive alkylation with isobutyraldehyde.…”

Section: Methodsmentioning

confidence: 99%

Bisphosphonated Benzoxazinorifamycin Prodrugs for the Prevention and Treatment of Osteomyelitis

et al. 2008

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Antimycobacterial Agents

Sensi¹,

Grassi²

2003

Burger's Medicinal Chemistry and Drug Discovery

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A few decades ago, the idea that a treatise on chemotherapy, to be published in this millennium, could include a chapter on antimycobacterial agents was probably considered acceptable mainly to illustrate the history of a strong successful fight against some human diseases present in the world since antiquity, such as tuberculosis and leprosy. In fact, starting from the middle of the last century, the introduction of chemotherapy for mycobacterial infections, together with improvements in the hygienic and nutritional conditions, brought about a dramatic decrease in the mortality and morbidity of these illnesses, with a trend toward their elimination. Unfortunately, these successes notwithstanding, mycobacterial infections still require particular attention as a worldwide, challenging health problem. In particular, in the last few years, an unexpected resurgence of tuberculosis has occurred in industrialized countries, probably because of the spread of HIV infection and the increasing and uncontrolled waves of immigration. Moreover, the emergence of multidrug resistant strains of Mycobacterium tuberculosis has made the older therapies largely ineffective. This chapter has been written for the medicinal chemist who wants to be updated on the situation in this area. The present knowledge of the biology of the pathogens, the mycobacteria, has been reviewed, taking into account the recent information on the genome sequence of M. tuberculosis and M. leprae. It also will review the information on the pathogenesis and epidemiology of the mycobacterial diseases. The antimycobacterial drugs used in therapy have been described in detail, mentioning some aspects of their discovery, but particularly their in vitro and in vivo activity, their mechanism of action, their side effects, and the general structure‐activity relationships in the frame of the chemical class to which they belong. Their use in therapy has been considered and evaluated when combined with other antimycobacterial drugs, when the combination is important for an improvement of efficacy and a decrease of probability of resistant strains selection. Some products in the early stage of development, as a starting point for new drugs that are needed, possibly acting on novel targets of the pathogens are also discussed.

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