Dicationic 2-fluorenonylcarbapenems: Potent anti-MRS agents with improved solubility and pharmacokinetic properties

被引：55

作者：

Greenlee, ML

Laub, JB

Rouen, GP

DiNinno, F

Hammond, ML

Huber, JL

Sundelof, JG

Hammond, GG

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Infect Dis, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Biochem, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 22期

关键词：

D O I：

10.1016/S0960-894X(99)00567-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and biological evaluation of a series of dicationic-substituted 2-fluorenonylcarbapenems is described. This class of compounds showed enhanced water solubility while maintaining potent activity against MRS. Introduction of a beta 1--methyl substituent was found to improve pharmacokinetics. (C) 1999 Elsevier Science Ltd. All rights reserved.

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收藏

页码：3225 / 3230

页数：6

相关论文

共 18 条

[1] The progressive intercontinental spread of methicillin-resistant Staphylococcus aureus [J].

Ayliffe, GAJ .

CLINICAL INFECTIOUS DISEASES, 1997, 24 :S74-S79

[2]

BRUMFITT W, 1994, DRUG EXP CLIN RES, V20, P215

[3] IN NITRO AND IN-VIVO ANTISTAPHYLOCOCCAL ACTIVITIES OF L-695,256, A CARBAPENEM WITH HIGH-AFFINITY FOR THE PENICILLIN-BINDING PROTEIN PBP 2A [J].

CHAMBERS, HF .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (02) :462-466

[4] Methicillin resistance in staphylococci: Molecular and biochemical basis and clinical implications [J].

Chambers, HF .

CLINICAL MICROBIOLOGY REVIEWS, 1997, 10 (04) :781-+

[5] THE DISCOVERY AND SYNTHESIS OF 2-BIPHENYLCARBAPENEMS ACTIVE AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCI [J].

DININNO, F ;

MUTHARD, DA ;

SALZMANN, TN ;

HUBER, J ;

KAHAN, J ;

KROPP, H .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (09) :945-948

[6]

Ehlert K, 1999, CURR PHARM DESIGN, V5, P45

[7] STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE 2-ARYLCARBAPENEM SERIES - SYNTHESIS OF 1-METHYL-2-ARYLCARBAPENEMS [J].

GUTHIKONDA, RN ;

CAMA, LD ;

QUESADA, M ;

WOODS, MF ;

SALZMANN, TN ;

CHRISTENSEN, BG .

JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (05) :871-880

[8] Species specificity of 2-aryl carbapenem-induced immune-mediated hemolytic anemia in primates [J].

Lankas, GR ;

Coleman, JB ;

Klein, HJ ;

Bailly, Y .

TOXICOLOGY, 1996, 108 (03) :207-215

[9] THE SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 2-CARBOLINYL-CARBAPENEMS - POTENT ANTI-MRSA/MRCNS AGENTS [J].

MEURER, LC ;

GUTHIKONDA, RN ;

HUBER, JL ;

DININNO, F .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (07) :767-772

[10] Synthesis and properties of 2-(naphthosultamyl)methylcarbapenems with potent anti-MRSA activity: Discovery of L-786,392 [J].

Ratcliffe, RW ;

Wilkening, RR ;

Wildonger, KJ ;

Waddell, ST ;

Santorelli, GM ;

Parker, DL ;

Morgan, JD ;

Blizzard, TA ;

Hammond, ML ;

Heck, JV ;

Huber, J ;

Kohler, J ;

Dorso, KL ;

St Rose, E ;

Sundelof, JG ;

May, WJ ;

Hammond, GG .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (05) :679-684