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A Chiral Benzoquinolizine-2-carboxylic Acid Arginine Salt Active against Vancomycin-Resistant Staphylococcus aureus

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Noel J. de Souza, Shrikant V. Gupte, Prasad K. Deshpande, Vijaya N. Desai, Satish B. Bhawsar, Ravindra D. Yeole, Milind C. Shukla, Jacob Strahilevitz,^† David C. Hooper,^† Bülent Bozdogan,^‡ Peter C. Appelbaum,^‡ Michael R. Jacobs,^§ Nitin Shetty, Mahesh V. Patel,* Rasendrakumar Jha, and Habil F. Khorakiwala

Wockhardt Limited, Wockhardt Research Centre, D-4, MIDC, Chikalthana, Aurangabad-431 210, India; Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114-2696; Hershey Medical Center, Hershey, Pennsylvania 17033; and Case Western Reserve University, Cleveland, Ohio 44106

J. Med. Chem., 2005, 48 (16), pp 5232–5242

DOI: 10.1021/jm050035f

Publication Date (Web): July 12, 2005

†

Massachusetts General Hospital.

‡

Hershey Medical Center.

Case Western Reserve University.

To whom correspondence should be addressed. Phone: 91-240-2483854. Fax: 91-240-2489219. E-mail: mpatel@ wockhardtin.com.

Abstract

There is an urgent medical need for novel antibacterial agents to treat hospital infections, specially those caused by multidrug-resistant Gram-positive pathogens. The need may also be fulfilled by either exploring antibacterial agents having new mechanism of action or expanding known classes of antibacterial drugs. The paper describes a new chemical entity, compound 21, derived from hitherto little known “floxacin”. The choice of the entity was made from a series of synthesized prodrugs and salts of the active chiral benzoquinolizine carboxylic acid, S-(−)-nadifloxacin. The chemistry, physicochemical characteristics, and essential bioprofile of 21 qualifies it for serious consideration as a novel drug entity against hospital infections of multi-drug-resistant Staphylococcus aureus, and its progress up to clinical phase I trials in humans is described.

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Published In Issue August 11, 2005
Received January 14, 2005

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Article

A Chiral Benzoquinolizine-2-carboxylic Acid Arginine Salt Active against Vancomycin-Resistant Staphylococcus aureus

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Piperazinobenzopyranones and Phenalkylaminobenzopyranones: Potent Inhibitors of Breast Cancer Resistance Protein (ABCG2)

Adenosine Kinase Inhibitors. 6. Synthesis, Water Solubility, and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidines Substituted at C4 with Glycinamides and Related Compounds

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