Novel therapeutic agents

As a result of the emergence of the extremely aggressive avian H5N1 influenza virus, the likelihood of a human influenza pandemic and the possible socioeconomic impact is now of major concern. In the absence of strain-independent anti-influenza drugs, there has been significant effort worldwide over the years in the quest for the discovery of novel therapeutic agents against all types of influenza. 

High throughput methods have increased our capacity for appropriate candidate compounds selection and also for developing libraries of novel compounds from which such candidates can be selected. Chapter 7 discusses the use of solid-phase synthesis for the high throughput production of peptides and other small molecules. In addition, as discussed in Chapter 6 on peptidomimetics, the swift production of novel leads holds considerable promise for future discovery of novel therapeutic agents. 

Drugs that act on the H3 receptor are being developed for the treatment of obesity, sleep disturbances, epilepsy and cognitive disorders. The ability of histamine to promote arousal, suppress appetite, elevate seizure threshold and stimulate cognitive processes implies that compounds able to enhance the release of neuronal histamine should mimic these effects. Several H3 antagonists currently in development demonstrate such activity and show promise as effective and novel therapeutic agents [40, 84-86]. Because H3 agonists suppress the release of... 

Yamabe N, Kang KS, Park CH, Tanaka T, Yokozawa T. (2009) 7-0-galloyl-D-sedoheptulose is a novel therapeutic agent against oxidative stress and advanced glycation endproducts in the diabetic kidney. Biol Pharm Bull 2il 657-664. 

In the search for structural diversity, and novel therapeutic agents, unique ring structures like the 1,2,5-thiadiazole have always captured the imagination of chemists. Often, as in the case of timolol (4), the interest is rewarded. In the early 1990s, a simple thiadiazole was appended to a penem in the development of the structure-activity relationships for a series of ) -lactamase inhibitors. The result was enhanced penetration of the bacterial membrane and a broader spectrum of activity versus clavulanic acid <9lJAN33l>. 

Based on the bio-molecular pathogenesis, novel therapeutic agents have been developed since 1998 for the treatment of DMARDs refractory autoimmune diseases. These biological-DMARDs include infliximab, etanercept, adalimumab, rituximab and abatacept. The biological-DMARDs anti TNF-a were first approved for therapy of refractory RA, followed by Crohn s disease, AS, and PsA. Scores of other biological DMARDs in Phase I, II, and III clinical trials in autoimmune diseases indicate that the number of these biological agents may ultimately become equal to the number of NSAIDs introduced over the last 50 years. 

Identification and functional characterization of genes Genomics is the identification of previously unknown human DNA sequences encoding natural human proteins with previously unknown medical use that can be used as targets in Drug Discovery to discover novel therapeutic agents or administered for therapeutic benefit. 

Microbial production of secondary metabolites is also an important source of novel therapeutic agents. However, the physiological and biochemical factors that determine the onset of production of a specific secondary metabolite in a particular species are incompletely understood. Generally, a range of analytical techniques, often elaborate, time-consuming and involving extensive sample pre-treatment, have to be developed in order to monitor the details of the metabolic changes and substrate consumption that accompany secondary metabolite production. In order to provide rapid multi-parametric information about the microbial fermentation process, H HPLC-NMR has been applied to characterise microbial metabolites directly in the broth supernatants from a... 

Nyce, J.W. 1997. Respirable antisense oligonucleotides as novel therapeutic agents for asthma and other pulmonary diseases. Expert Opin. Investig. Drugs 6 1149-1156. 

If accurate determination of chemosensitivity were predictable by gene expression analysis, the overall number of patients receiving cytotoxic treatment unnecessarily would decrease, and the overall survival benefit derived per patient treated would increase accordingly. Large increases in the absolute survival of patients diagnosed with breast cancer, however, will require the development of novel therapeutic agents. 

In recent years, a confluence of spectacular advances in chemistry, molecular biology, genomics, and chemical technology, and the cognate fields of spectroscopy, chromatography, and crystallography have led to the discovery and development of numerous novel therapeutic agents for the treatment of a wide spectrum of diseases. 

The treatment of narcolepsy with psychostimulants such as amphetamine 2 (Adderall), and methylphenidate 3 (Ritalin) has been reported.3 However, these are schedule 2 DEA-controlled substances and have a potential risk of abuse, overdose, and dependence, which present substantial barriers to widespread use.4 As a result, there has been a significant effort to identify novel therapeutic agents for the... 

Over the past two decades, advances in peptide and protein manufacturing technologies have led to the production of many novel therapeutic agents (1). These new drug candidates are commonly administered by injection to avoid the complexities associated with either oral or pulmonary delivery. Proteolysis in the digestive tract is the primary obstacle to oral protein delivery, and reproducible delivery to the deep lung is the primary obstacle to pulmonary peptide... 

The discovery and development of novel therapeutic agents by the pharmaceutical industry has afforded physicians an extensive armamentarium to fight a wide range of human disease. Of course there remains the opportunity for even more effective drugs with... 

In recent years multicomponent reactions have been extensively utilized to produce libraries of heterocyclic molecules with biological activity against a variety of targets. The majority of these compounds were tested for their anticancer, antioxidant and antimicrobial properties and numerous promising compounds were identified and were further evaluated. With the continuous development of new multicomponent reactions and combinations of MCRs with subsequent transformations, this area of research holds great promise for the discovery of novel therapeutic agents. 

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