Design and synthesis of endoperoxide antimalarial prodrug models

被引：51

作者：

O'Neill, PM ^{[1
]}

Stocks, PA

Pugh, MD

Araujo, NC

Korshin, EE

Bickley, JF

Ward, SA

Bray, PG

Pasini, E

Davies, J

Verissimo, E

Bachi, MD

机构：

[1] Univ Liverpool, Robert Robinson Labs, Dept Chem, Liverpool L69 7ZD, Merseyside, England

[2] Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel

[3] Univ Liverpool Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2004年 / 43卷 / 32期

关键词：

antimalarial agents; chalcones; combination chemotherapy; cysteine protease inhibitors; endoperocides;

D O I：

10.1002/anie.200453859

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A masked combination chemotherapy which relies on the embedding of a number of active components, in a latent form, within a single endoperoxidic chemical entity is the aim of the research presented. The approach is illustrated by means of purposely designed bicyclic endoperoxide prodrug prototypes 1 and subsequently validated through the study of model compounds 2 (Ar= Ph, p-FC 6H4, p-ClC6H4.

引用

页码：4193 / 4197

页数：5

共 69 条

[1] A highly stereoselective synthesis of D-erythrose derivatives by one-carbon homologation of 2,3-O-isopropylidene-D-glyceraldehyde with (R)-methyl p-tolyl sulfoxide [J].

Arroyo-Gómez, Y ;

Rodríguez-Amo, JF ;

Santos-García, M ;

Sanz-Tejedor, MA .

TETRAHEDRON-ASYMMETRY, 2000, 11 (03) :789-796

[2] REACTION OF ANTIMALARIAL ENDOPEROXIDES WITH SPECIFIC PARASITE PROTEINS [J].

ASAWAMAHASAKDA, W ;

ITTARAT, I ;

PU, YM ;

ZIFFER, H ;

MESHNICK, SR .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (08) :1854-1858

[3] Synthesis and in vitro antimalarial activity of sulfone endoperoxides [J].

Bachi, MD ;

Korshin, EE ;

Ploypradith, P ;

Cumming, JN ;

Xie, SJ ;

Shapiro, TA ;

Posner, GH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (08) :903-908

[4] A short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic β-sulfonyl-endoperoxides [J].

Bachi, MD ;

Korshin, EE ;

Hoos, R ;

Szpilman, AM ;

Ploypradith, P ;

Xie, SJ ;

Shapiro, TA ;

Posner, GH .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (12) :2516-2533

[5]

Bachi MD, 1998, SYNLETT, P122

[6] Synthesis and reactions of antimalarial bicyclic peroxides [J].

Bachi, MD ;

Korshin, EE ;

Hoos, R ;

Szpilman, AM .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2000, 37 (03) :639-646

[7] In vitro activities of DU-1102, a new trioxaquine derivative, against Plasmodium falciparum isolates [J].

Basco, LK ;

Dechy-Cabaret, O ;

Ndounga, M ;

Meche, FS ;

Robert, A ;

Meunier, B .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (06) :1886-1888

[8] The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin [J].

Bhisutthibhan, J ;

Pan, XQ ;

Hossler, PA ;

Walker, DJ ;

Yowell, CA ;

Carlton, J ;

Dame, JB ;

Meshnick, SR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :16192-16198

[9] Malaria: New Chemotherapeutic Peroxide Drugs [J].

Borstnik, Kristina ;

Paik, Ik-hyeon ;

Posner, Gary H. .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2002, 2 (06) :573-583

[10] Characterization of the main radical and products resulting from a reductive activation of the antimalarial arteflene (Ro 42-1611) [J].

Cazelles, J ;

Robert, A ;

Meunier, B .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (18) :6776-6781

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