Pharmaceuticals antibacterial/antibiotic

Beale JM Jr (2004) Antibacterial antibiotics. In Block JH, Beale JM Jr (eds) Wilson and Gisvold s textbook of organic medicinal and pharmaceutical chemistry, 11th edn. Lippincott, Williams Wilkins, Philadelphia p 299... 

For example, molds and bacteria produce substances that prevent other organisms from growing in their vicinity. The famous Penicillium mold led, via the pharmaceutical industry, to penicillin. However, penicillin was not stable in the acidic environment of the stomach, and so compounds were synthesized by chemists to produce a range of useful semisynthetic penicillin analogues. An example of the use of analogues to develop new antibacterial antibiotics is provided in Chapter II-14, on the development of moxifloxacin. 

Vancomycin is most often the antibiotic of last resort for the treatment of resistant bacterial strains, however, bacterial strains resistant to vancomycin are now emerging [19]. The health threat posed by these strains has led to intense research into both the mechanism by which resistance develops and the development of pharmaceutical antibacterial agents with novel modes of action. 

Table 15 gives a sampling of other pharmaceuticals derived from hydraziae. Cefazolin, a thiadiazole tetrazole derivative, is one of the most widely used antibacterial dmgs in U.S. hospitals (see Antibiotics, P-LACTAMs). Procarbazine, an antineoplastic, is a monomethyUiydrazine derivative (220). Fluconazole has shown some promise in the treatment of AIDS-related fungal infections. Carbidopa is employed in the treatment of Parkinson s disease. FurazoHdone is a veterinarian antibacterial. 

On a worldwide basis, total pharmaceutical sales for 1983 were 71 biUion, antibiotic sales totaled 9.2 biUion, and cephalosporins accounted for 1.2 biUion, or 13% of the antibacterial market (87). By 1986 the worldwide antibiotic market was valued at around 11 biUion and cephalosporins... 

Penicillin, the first (3-lactam antibiotic, marked the beginning of a revolutionary period of successful treatment of infectious disease and, in many respects, the beginning of the modern pharmaceutical industry. With more than 6 decades of history, the (3-lactam core remains an important antibacterial pharmacophore. 

Doripenem (20 Finibax /DoribaxTM Shionogi Co. Ltd., 2005 Johnson Johnson, 2007), a synthetic carbapenem-type [3-lactam, has appeared to be an ultra-broad spectrum injectable antibiotic. It was launched in Japan by Shionogi Co. Ltd. in the year 2005 as a broad antibacterial spec-trum. In October 2007, Johnson Johnson (J J) (formerly Peninsula Pharmaceuticals) obtained formal FDA approval for the use of doripenem... 

Rifamycin- quinolone heterodimer Antibiotics CBR-2092 (156) Antibacterial Bcerts antimicrobial activity through combined effects on RNA polymerase, DNA topoisomerase IV and DNA gyrase Phase Ila (treatment of infections caused by Gram-positive cocci) Cumbre Pharmaceuticals 819, 820... 

WAP-8294A2 (JA-002) (157) Antibiotic WAP-8294A2(157) Antibacterial (MRSA infections and acne) Interacts selectively to membrane phospholipids, causing sever damage to bacterial membrane Various Phase I/II trials (gel, cream, injectable form) aRigen Pharmaceuticals 821-824... 

The industrial production of penicillin by Pfizer in 1943 transformed the chemistry of natural products. Microbiology became its field and pharmaceutical research became its leading trend. The main driving force behind the research of the chemistry of natural products was and still remains to be human health care. Since the advent of antibiotics, many sources of natural chemicals, such as plants, fungi and bacteria, have been searched for antibacterials, anticancer products, immuno-suppressors and chemicals that affect the human psyche. This research was so successful that, even today, more than half of all pharmaceuticals are either natural products or derived from, or inspired by them. The market of antibiotics alone was ca. US 30 billion in 2005. The majority of antibiotics is produced by submerged fermentation of filamentous microorganisms such as soil prokaryotic actinomycetes and eukaryotic moulds, ascomycetes. 

With the exception of S-metolachlor, all the molecules listed under the column Final Target are used in pharmaceutical formulations. Dilitiazem is a Ca2+ antagonist, while Cilazapril is an angiotensin-converting enzyme inhibitor. Levofloxacin is an antibacterial, and cilastatin is used as an in vivo stabilizer of the antibiotic imipenem. S-metolachlor is a herbicide sold under the trade name of DUAL MAGNUM. Although the structures of the final targets are more complex than those of the intermediates, enantioselective syntheses of the intermediates are the most crucial steps in the complex synthetic schemes of these molecules. 

Extensive early studies of in vitro and in vivo structure-activity relationships within the leucomycin family revealed correlations between the number and type of O-acyl substituents and the compounds antibacterial potency, efficacy in treating experimental infections, and serum antibiotic concentrations [26]. Consequently, esterification of all hydroxyl groups within several leucomycin-related macrolides was conducted to find derivatives with better antibiotic activity and pharmaceutical properties (such as greater water solubility and masking their extremely bitter taste). From such investigations with midecamycin, miokamycin was synthesized and characterized as a useful new macrolide antibiotic [24, 27]. It has now been commercially launched in several countries [5]. 

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