Lead acetylsalicylate

Lead acetylsalicylate is a combustion-modifying additive, especially so in rocket propellants based on double base powder -> Double Base Propellants. 

Salicin is an (9-glycoside of a phenol, namely salicyl alcohol. Salicin is a natural antipyretic and analgesic found in willow bark, and is the template from which aspirin (acetylsalicylic acid, see Box 7.13) was developed. Prunasin from cherry laurel is an example of a cyanogenic glycoside, hydrolysis of which leads to release of toxic HCN (see Box 7.7). It is the (9-glucoside of the alcohol mandelonitrile, the trivial name for the cyanohydrin of benzaldehyde. It is the further hydrolysis of mandelonitrile that liberates HCN. 

Ester hydrolysis does not invariably lead to inactive metabolites, as exemplified by acetylsalicylic acid. The cleavage product, salicylic acid, retains pharmacological activity. In certain cases, drugs are administered in the form of esters in order to facilitate absorption (enalapril enalaprilate testosterone undecanoate testosterone) or to reduce irritation of the gastrointestinal Lullmann, Color Atlas of Pharmacology... 

Two different pathways lead from arachidonate to prostaglandins, prostacyclins, and thromboxanes, on the one hand, or leuko-trienes on the other. The key enzyme for the first pathway is prostaglandin synthase [2]. Using up O2, it catalyzes in a two-step reaction the cyclization of arachidonate to prostaglandin H2, the parent substance for the prostaglandins, prostacyclins, and thromboxanes. Acetylsalicylic acid (aspirin) irreversibly ace-tylates a serine residue near the active center of prostaglandin synthase, so that access for substrates is blocked (see below). 

Drugs in solution formulations may be more susceptible to chemical reactions leading to degradation. The most common reactions are hydrolysis, oxidation, and reduction. Usually, the reaction rate or type is inLuenced by pH. For example, the hydrolysis of acetylsalicylic acid (aspirin) is pH dependent, and its pH-rate proLle shows a large and complex variation dfrls to four distinct mechanistic patterns (Alibrandi et al., 2001). Therefore, it is essential to monitor and understand the chemical stability of the drug in pH-adjusted formulations. 

Non-ionic diffusion can also produce unwanted effects, as in the case of aspirin (acetylsalicylic acid figure 2.8b). In the acidic milieu of the stomach, this molecule will be protonated and thus uncharged, which promotes its diffusion into the cells of the stomach mucous membrane. Inside the cell, the pH is very close to neutral, which will lead to deprotonation of aspirin. Diffusion of the deprotonated (charged) form out of the cell will be much slower than entry, so that aspirin will accumulate inside the cells to con-... 

The well-known drug Aspirin can demonstrate the various stages in the life of a drug substance. It was known since ancient times that the bark and leaves of the willow tree can provide relief from pain and fever. In 1832, the German chemist Piria isolated salicylic acid as the active substance in the plant material. Salicylic acid became the lead substance for further development. Soon a synthetic route was developed that replaced the tedious extraction process. Salicylic acid was used as a pain remedy, but because of its high acidity it had severe side effects when applied orally. In 1887, Felix Hoffmann, a chemist at Bayer AG, realized that the ester form of salicylic acid, acetylsalicylic acid, had fewer side effects and was even more efficacious than the free acid. The Bayer Company marketed the ester under the trade name Aspirin, which soon became the number one selling drug worldwide and is still a synonym for pain relief today. 

A century after its introduction, acetylsalicylic acid (aspirin) is by far the most commonly used analgesic, sharing its leading position with the relative newcomer paracetamol (acetaminophen), and notwithstanding the fact that other widely used compounds of their class, like ibuprofen and naproxen, have in recent years been introduced in over-the-counter versions. Both are also still being prescribed by physicians and are generally used for mild to moderate pain, fever associated with... 

See also Acetylsalicylic Acid Butyl Nitrite Cancer Chemotherapeutic Agents Carbon Disulfide Cisplatin Lead Mercury Tin Trichloroethylene. 

The traditional method of drag development, at least in this century, has been to develop leads by first using, and then by isolating and identifying, the active chemical constituents from natural products, some of which may have been medicinally in use since antiquity. With the advent of modem organic chemistry some of these purified compounds were used directly (e.g., morphine, cocaine, atropine, quinine), and, once their chemical structures were ascertained, they became leads for hoped-for chemical modifications to achieve improved efficacy, less toxicity, or, at least, higher potency (e.g., dihydromorphinone, homatropine, acetylsalicylic acid). 

The relationship between hyaluronic acid, hyaluronidase and rheumatic diseases has been discussed by Smith, who examined the theory that the therapeutic action of salicylate in rheumatic fever might be due to inhibition of increased hyaluronidase activity, but concluded that there was little evidence to support this view. Recent work by others tends to support these conclusions . Nevertheless, the subcutaneous injection of hyaluronidase into the foot of the rat leads to the development of oedema which can be suppressed by anti-inflammatory drugs - . Dewes investigated the inhibition produced by a number of antirheumatic drugs administered subcutaneously and found phenylbutazone, amidopyrine, phenazone and cinchophen active, sodium salicylate less active, and acetylsalicylic acid virtually inactive. All the compounds were, however, given in high doses. Rechenberg has reviewed the actions of phenylbutazone on hyaluronidase in vitro, and on hyaluronidase-induced tissue permeability . ... 

Acetylsalicylic acid (ASA, Aspirin ) is a common analgetic, anti-inflammatory, and antipyretic drug. Because of its acidity (pA a = 3.49) it can also cause some irritations which can prompt side reaction such as heartburn and vomiting when orally administered. Moreover, when regularly taken, it may lead to mucosal irritation and bleeding in the gastrointestinal tract, and also may lead to gastric... 

Stewart Adams and John Nicholson at the Boots Company in Nottingham took acetylsalicylic acid as a lead template and looked for related anti-inflammatory structures, which would be devoid of the ASA-related side-effect. In 1955, they discovered that their anti-inflammatory compounds reduced skinreddening (erythema) in guinea-pigs, caused by ultraviolet irradiation. Thereby they had foimd a simple and feasible assay system to test a whole host of compounds. In 1961, out of a group of several hundred substances they were able to select the one, which was introduced to the British market in 1969 under the name ofibuprofen (Fig. 5.83). [180]... 

A linear biosynthetic route, which is not influenced by acetylsalicylic acid, leads by means of lipoxygenase via a simple addition of oxygen to an epoxide, which is transformed by addition of water or glutathione into the various leukotrienes. 

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