Drug hunters

This chapter is the first chapter in this book and serves as an introduction The first section of this chapter starts with a discussion of what is a medicinal chemist In this chapter the reader will notice far more attention to the people aspect of the discipline of medicinal chemistry than will be found in later chapters. This is by design. When expert practitioners in the field discuss success in medicinal chemistry the focus is usually very much on the person rather than on the technology. We admire the persistent drug hunters. We remember the individuals who do not give up easily. We appreciate those individuals with the interpersonal skills that facilitate an effective therapeutic project team. We admire those medicinal chemists who think out of the box and come up with the insights that transform a program. In this introduction I have tried to give some credit to this people factor. 

Another dimension of complexity must be layered on top of this description the demand for these forms of data is growing as drug hunter teams become increasingly reliant on ADME/Tox feedback during the course of their lead optimization programs. Naturally, this growing demand for data is a welcome trend, as it indicates broader opportunity for impact, but of course increased demand exacerbates the complexity of the process. 

Many challenges are encountered on the path to conversion of a drug lead with an attractive new mode of action into a clinically useful therapeutic agent. As well appreciated by drug hunters, more risk is associated vdth the development of an NC E than an improved representative from an already widely used and proven class of antibiotics (with the combination of clinical benefits and appropriate toxicological... 

Beyond nucleic acids, prediction of protein structure is becoming a major effort for drug hunters in the pharmaceutical and biotechnology industries. There are a series of links to research into protein folding from various academic groups as shown in Table 11.4. 

Hunter, J., Hirst, B. H., Intestinal secretion of drugs the role of P-glycoprotein and related drug efflux systems in limiting oral drug absorption, A dr. Drug Del. Rev. 1997, 25, 129-157. 

The chemical structures and biological activities of hundreds of opioid analgesics derived from the prototype opioid drug morphine are most comprehensively described in two books published in 1986, one entitled Opioid Analgesics, Chemistry and Receptors by Casy and Parfitt [1] and the other entitled Opiates by Lenz et al. [2]. Follow-up articles include those by Casy in 1989, entitled Opioid Receptors and their Ligands Recent Developments [3] which also includes sections on opioid peptides, affinity labelling and opioid receptor subtypes Rees and Hunter in 1990 [4] covering the... 

Jick H, Hohnes LB, Hunter JR, et al. First trimester drug use and congenital disorders. JAMA 1981 246 343-6. 

Idursulfase (Elaprase) is a drug used to treat mucopolysaccharidosis II or Hunter syndrome. It is a lysosomal storage disease caused by iduronate-2-sulfatase deficiency. Idursulfase is a purified form of iduronate-2-sulfatase produced by recombinant DNA technology in a human cell line. The drug provides clinically important benefits to Hunter syndrome patients. After intravenous infusion Idursulfase is eliminated by peptide hydrolysis with an elimination half-life of 45 minutes. The most common adverse events are hypersensitivity reactions, pyrexia, headache and arthralgia. 

Meyer A Psychobiology A Science of Man. Springfield, IL, Charles C Thomas, 1957 Meyer EM, de Eiebre CM, Hunter BE, et al Effects of anabaseine-related analogs on rat brain nicotinic receptor binding and on avoidance behaviors. Drug Dev Res 31 127-134, 1994... 

Peng CC, Glassman PA, Trilli LE, Hayes-Hunter J, Good CB. Incidence and severity of potential drug-dietary supplement interactions in primary care patients an exploratory study of 2 outpatient practices. Arch Intern Med 2004 164(6) 630-636. 

Hunter AC, Moghimi SM. Therapeutic synthetic polymers a game of Russian roulette Drug Dis Today 2002 7(19) 998. 

Because of the effects and mythological significance of Yage, a number of ritual occasions and annual feasts have developed that center around the drug. One of the most important of these is the victory feast of the Jivaro head-hunters, described by Karsten (1935), which follows the conquest of an... 

FIGURE 1.11 A scheme of the various absorption routes across the intestinal epithelium and cellular barriers to xenobiotics absorption. A, Transcellular absorption (plain diffusion) B, paracellular absorption C, carrier-mediated transcellular absorption D, facilitated diffusion E, the MDR and P-gp absorption barrier and F, endocytosis. (From Hunter, J. and Hirst, B.H., Adv. Drug Deliv. Rev., 25, 129, 1997. With permission.)... 

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