Central nervous system , heterocyclic

Heterocyclic amines have also been used for aminolysis. Subsequent cyclization of the acylamino amides leads to imidazolones that show a diverse range of biological activities as antibacterial, antifungal, antiviral, antihelmintic, and anti-Parkinsonian agents, as well as central nervous systems (CNS) stimulants. 

Benzodiazepine derivates, seven-membered rings with 2 N atoms in 1,4 position are the pivotal structures of the benzodiazepine class of breakthrough CNS (central nervous system) drugs such as Librium and Valium. The most recent drug in this class, Sepracor s Lunesta (eszopiclone), is composed almost entirely of A-heterocyclics. Like most modern drugs, esczopi-clone also has a chiral center ... 

A large number of compounds in which thiophene was fused to other heterocyclic rings have been investigated, notably in the central nervous system agents. For example, the benzodiazepine derivative (365) is reported to be more active than Clozapine in conditioned avoidance response tests in the rat (80JMC878). The activity of such fused-ring thiophenes has been reviewed (81JHC1277). 

HU-211 is highly liposoluble, which makes it readily accessible to the central nervous system since it readily crosses the blood brain barrier. However, its poor solubility in water hampers development of formulations suitable for i.v. administration. In order to overcome this drawback, Popp et al. have prepared a series of water-soluble salts of glycinate esters (attached to the allylic hydroxyl) and salts of amino acid esters containing tertiary and quaternary nitrogen heterocyclics (attached to the phenolic hydroxyl) (see Figure 5.5) [201, 202]. Most of the new compounds were relatively soluble in water or 10% aqueous ethanol, and showed neuroprotective properties, attributed to the parent compound, formed on hydrolysis of the esters in vivo. 

Alkaloids are classified according to their heterocyclic rings. For example, cocaine, a central nervous system stimulant, and atropine, a muscle relaxant, are examples of the tropane alkaloids in which a nitrogen appears in a bridge of a seven-membered ring structure. Nicotine, the addictive and toxic component of tobacco, is an example of the pyridine alkaloids in which a nitrogen appears as a member of a six atom aromatic ring. (Nicotine is an effective insecticide.) The addictive... 

The heterocyclic compounds of oxygen that are largely used as solvents, tetrahydro-furan and 1,4-dioxane, are an irritant to the eyes and respiratory tract, a depressant to the central nervous system, and exhibit a low order of toxicity. Exposure to high concentrations, however, may cause injury to the kidney and liver in humans. 

It will be evident from the ensuing chapters that heterocycles play an extremely important role in drug discovery, in general, and in medicinal chemistry, in particular. Heterocycle-containing drugs are found in all therapeutic areas including cardiovascular and metabolic diseases, central nervous system (CNS), anti-cancer, anti-inflammatory, anti-ulcer, anti-infective drugs, and so on. 

Indole is perhaps the most visible heterocycle in all of chemistry. Since Adolf von Baeyer proposed the structure of indole as a heteroaromatic compound 140 years ago, indole has embodied a myriad of natural products, pharmaceutical agents, and a growing list of polymers. In the human body, serotonin modulates 5-hydroxytryptamine (5-HT), a monoamine neurotransmitter primarily found in the gastrointestinal (GI) tract and central nervous system (CNS), and modulates vasoconstriction and many brain activities. Melatonin regulates circadian rhythms, most noticeably, sleep. Tryptamine is closely related to melatonin and the amino acid tryptophan. 

There are mainly five disguised enemies in our society cancer, diabetics, AIDS, cardiovascular disease (CVD), and central nervous system (CNS) diseases. Figures 2-6 support the fact that the frontline drugs against all these five deadly diseases are heterocyclic derivatives. This clearly indicates that there is an increasing demand of synthesizing novel heterocyclic molecules. 

FIGURE 6 Frontline drugs for central nervous system diseases containing heterocyclic scaffold in their core. 

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