Medicinal chemistry therapeutic compounds

Ghose, A. K., Crippen, G. M. The distance geometry approach to modeling receptor sites In Comprehensive Medicinal Chemistry. The Rational Design, Mechanistic Study and Therapeutic Application of Chemical Compounds, Hansch, C.,... 

The successes of prodrug design are many, and a large variety of such compounds have proven their therapeutic value. When discussing this multidisciplinary field of medicinal chemistry, several complementary viewpoints can be adopted, as listed in Table 1.2. 

Hansch, C., Sammes, P.G., and Taylor, J.B. (Eds.) Comprehensive Medicinal Chemistry The Rational Design, Mechanistic Study, and the Therapeutic Application of Chemical Compounds. Pergamon Press, Oxford, 1990. 

The identification of the first small molecule HDAC inhibitors in the late seventies triggered an exponential growth in medicinal chemistry activity. Three decades and many thousand compounds later, the availabiUty of diverse HDAC inhibitors such as short-chain fatty acids, hydroxamic acids, benzamides and tetracyclic peptides, has not only enabled the elucidation of the catalytic mechanism underlying the deacetylating capacity of HDACs, but has also assisted in the investigation of the biological role of the various HDAC subtypes. Furthermore, HDAC inhibitors are currently being evaluated in the clinic and have shown therapeutic potential in the treatment of cancer. 

Together, the chemistry of codeine and the drug s absorption into the bloodstream, distribution to various compartments and tissues in the body, metabolism (breakdown of the parent compound into smaller molecules, or metabolites), and excretion are intimately related to how codeine exerts its medicinal or therapeutic effects. Codeine s chemical properties and pharmacologic characteristics explain how, figuratively speaking, a spoonful of codeine can relieve pain, suppress cough, or act as an antidiarrheal. 

Medicinal chemistry has many examples of the development of successful therapeutics based on an exploration of endogenous compounds. The treatment of diabetes mellitus, for example, is based upon the administration of insulin, the hormone that is functionally deficient in this disease. The current treatment of Parkinson s disease is based upon the observation that the symptoms of Parkinson s disease arise from a deficiency of dopamine, an endogenous molecule within the human brain. Since dopamine cannot be given as a drug since it fails to cross the blood-brain barrier and enter the brain, its biosynthetic precursor, L-DOPA, has been successfully developed as an anti-Parkinson s drug. Analogously, the symptoms of Alzheimer s disease arise from a relative deficiency of acetylcholine within the brain. Current therapies for Alzheimer s-type dementia are based upon the administration of cholinesterase... 

Although steroids have been studied for many years, steroid hormones continue to be a rich area of medicinal chemistry study. Steroids continue to be evaluated for their therapeutic role in the treatment of cancer, especially malignancies whose growth characteristics are hormonally responsive. In recent years, the increased recognition of the role of steroids in the brain has resulted in ongoing projects to evaluate steroids as general anasthetics and anticonvulsants. Also, the search for compounds that bind to steroid receptors, but which are not steroidal in their molecular structure, is another important area of research. 

Historically, terpenes have enjoyed a role as symptom-relieving therapeutics. Camphor and carvone (spearmint oil) have been used as soothing agents in the past history of pharmaceutical compounds. More recently, the role of terpenes in biochemistry has been more fully appreciated. P-Carotene, for example, may be cleaved into two units of vitamin A. Other terpenes, such as geraniol, are now recognized as pheromones (a chemical secreted by one individual of a given species in order to elicit a response in another individual of the same species). Pheromones are of interest in medicinal chemistry for a variety of indications for instance, attractant pheromones can be used for the control of insects known to spread human disease. 

There are three major sources for a typical corporate compound collection project-specific compounds accumulated over a long period of time through medicinal chemistry efforts for various therapeutic projects, individual compounds from commercial sources, and compounds from combinatorial chemistry. In practice, compound collections are often divided into subsets, for example, the diverse subsets for general HTS and target-focused subsets (such as kinase libraries or GPCR libraries). For library design, diversity and similarity are generally built into the libraries of compounds to be synthesized and/or purchased (73). 

D. G. Cooper, R. C. Young, G. J. Durant, and C. R. Ganellin in Comprehensive Medicinal Chemistry the Rational Design, Mechanistic Study Therapeutic Application of Chemical Compounds, C. Hansch (ed.), Pergamon Press, Oxford, U.K., 1990, pp 323—421. 

Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. Furthermore, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. For example, the unnatural L-nucleoside 1 inhibits reverse transcriptase and shows potent and selective anti-AIDS activity,1 and the unsaturated neuraminic acid analogue 2 is the sialidase-inhibitory... 

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