Synthesis and antibacterial activity of C2-fluoro, C6-carbamate ketolides, and their C9-oximes

被引：19

作者：

Xu, XD ^{[1
]}

Henninger, T ^{[1
]}

Abbanat, D ^{[1
]}

Bush, K ^{[1
]}

Foleno, B ^{[1
]}

Hilliard, J ^{[1
]}

Macielag, M ^{[1
]}

机构：

[1] Johnson & Jonhson Pharmaceut Res & Dev LLC, Antimicrobial Agents Res Team, Raritan, NJ 08869 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 04期

关键词：

ketolide; carbamate; oxime; fluoro ketolide; resistant bacteria;

D O I：

10.1016/j.bmcl.2004.12.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel C6-carbamate ketolides with C2-fluorination and C9-oximation have been synthesized. The best compounds in this series displayed MIC values of 0.03-0.12 mug/mL against streptococci containing erm and mef resistance determinants and 2-4 mug/mL against Haemophilus influenzae. Several compounds also showed measurable activity against erm(B)-containing enterococci with MIC values of 2-8 mug/mL. In vivo activity was adversely affected by fluorination, possibly as a result of increased serum protein binding. (C) 2005 Elsevier Ltd. All rights reserved.

引用

页码：883 / 887

页数：5

共 23 条

[1] Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives):: A new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens [J].

Agouridas, C ;

Denis, A ;

Auger, JM ;

Benedetti, Y ;

Bonnefoy, A ;

Bretin, F ;

Chantot, JF ;

Dussarat, A ;

Fromentin, C ;

D'Ambrières, SG ;

Lachaud, S ;

Laurin, P ;

Le Martret, O ;

Loyau, V ;

Tessot, N .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (21) :4080-4100

[2] Synthesis and antibacterial activity of novel bifunctional macrolides [J].

Akritopoulou-Zanze, I ;

Phelan, KM ;

Marron, TG ;

Yong, H ;

Ma, ZK ;

Stone, GG ;

Daly, MM ;

Hensey, DM ;

Nilius, AM ;

Djuric, SW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (14) :3809-3813

[3] Synthesis and antibacterial activity of 6-O-arylpropargyl-9-oxime-11,12-carbamate ketolides [J].

Beebe, X ;

Yang, F ;

Bui, MH ;

Mitten, MJ ;

Ma, ZK ;

Nilius, AM ;

Djuric, SW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (10) :2417-2421

[4] Ketolides - telithromycin, an example of a new class of antibacterial agents [J].

Bryskier, A .

CLINICAL MICROBIOLOGY AND INFECTION, 2000, 6 (12) :661-669

[5] 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A synthesis and in vitro activity [J].

Chen, SX ;

Xu, XD ;

Yu, LX .

JOURNAL OF ANTIBIOTICS, 2001, 54 (06) :506-509

[6] β-keto-ester chemistry and ketolides.: Synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides [J].

Denis, A ;

Bretin, F ;

Fromentin, C ;

Bonnet, A ;

Piltan, G ;

Bonnefoy, A ;

Agouridas, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (17) :2019-2022

[7] Synthesis of 9-oxime-11,12-carbamate ketolides through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide [J].

Denis, A ;

Pejac, JM ;

Bretin, F ;

Bonnefoy, A .

BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (11) :2389-2394

[8] Novel fluoroketolides: synthesis and antibacterial activity [J].

Denis, A ;

Bonnefoy, A .

DRUGS OF THE FUTURE, 2001, 26 (10) :975-984

[9] ABT-773: a new ketolide antibiotic [J].

Dougherty, TJ ;

Barrett, JF .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2001, 10 (02) :343-351

[10] Reductive N-alkylation of amides, carbamates and ureas [J].

Dubé, D ;

Scholte, AA .

TETRAHEDRON LETTERS, 1999, 40 (12) :2295-2298

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