Pharmaceuticals pyridine derivatives

Acetaldehyde is an important intermediate in the production of acetic acid, acetic anhydride, ethyl acetate, peracetic acid, pentaerythritol, chloral, glyoxal, and alkylamines. Acetaldehyde is also a valuable intermediate in the manufacture of dyes, pharmaceuticals, pyridine derivatives, and other chemical products. 

Natural products biosynthesis, 1, 83-109 fused oxirane rings, 7, 192 fused thiirane rings, 7, 192-193 as insecticides, 1, 198 nomenclature, 1, 28-31 oxiranes, 7, 120 as pharmaceuticals, 1, I46-I56 pyridine derivatives... 

Effectively, this is another example of the addition of a functional aromatic compound to an alkene, as the Murai reaction, but the mechanism is different. Alkyl substituted pyridine derivatives are interesting molecules for pharmaceutical applications. The a-bond metathesis reaction is typical of early transition metal complexes as we have learnt in Chapter 2. 

The commercial availability of basic pyridine derivatives has encouraged a tremendous amount of research into pharmaceutically active compounds. Two reviews in particular list a large number of medicinal compounds (B-80MI20900,77CZ389) based on the pyridine ring. Likewise, the occurrence of benzopyridine natural products with chemotherapeutic activity has stimulated the production of synthetic materials from aromatic amine precursors. Some important examples are presented below. 

Historically, the use of pyridine derivatives as cyclization substrates in the synthesis of fused heterocyclic systems has had great impact in pharmaceuticals, metal-chelation chemistry and other applications. Fused heterocycles incorporating different regioisomers... 

Pyridine was first isolated, like pyrrole, from bone pyrolysates. Its name is derived from the Greek for fire (pyr) and the suffix idine used to designate aromatic bases. Pyridine can also be formed from the breakdown of many natural materials in the environment. Pyridine is used as a solvent, in addition to many other uses including products such as pharmaceuticals, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. Structurally, pyridine derivatives can range in complexity from the relatively simple monosubstituted pyridine, nicotine (1), to the highly elaborated sesquiterpene pyridine alkaloids, chuchuhuanines [1] (2). 

The apparent acid dissociation constants (p s)Ka) of two water-insoluble drugs, ibuprofen and quinine, were determined pH-metrically in ACN water, dimethyl-formamide water, DMSO water, 1,4-dioxane-water, ethanol water, ethylene glycol-water, methanol water, and tetrahydrofuran water mixtures. A glass electrode calibration procedure based on a four-parameter equation (pH = alpha-i- SpcH -i-jH[H+] -i-jOH[OH ]) was used to obtain pH readings based on the concentration scale (pcH). We have called this four-parameter method the Four-Plus technique. The Yasuda Shedlovsky extrapolation p s)K a + log [H2O] = A/epsllon -1- B) was used to derive acid dissociation constants in aqueous solution (pKa). It has been demonstrated that the pK a values extrapolated from such solvent-water mixtures are consistent with each other and with previously reported measurements. The suggested method has also been applied with success to determine the pKa values of two pyridine derivatives of pharmaceutical Interest. Spectrometric, ultraviolet (UV) ... 

Pyridine derivatives are precursors of many chemical products of medicinal, agricultural, and industrial importance. Pyridine itself is used not only as a solvent, but also as a starting material for pharmaceuticals, herbicides, insecticides, and fungicides. a-Picoline is a precursor for 2-vinylpyridine which is used in the production of an adhesive for textile tire cord. The major use of y-picoline is in the production of isonicotinic hydrazide, an antituberculosis agent. / -Picoline and 2-methyl-5-ethylpyridine are important intermediates in the production of two members of the vitamin B family, nicotinamide, and nicotinic acid (also known as vitamin B3). All this shows there is a substantial need for the production of picolines. The following text describes a novel route to a-picoline which might in the future lead to new processes. 

Pyridine derivatives are important as pharmaceuticals. Nicotinic acid derivatives are used as vasodilators, anticoagulants and hypolipidaemic agents. Derivatives of isonicotinic acid (pyridine-4-carboxylic acid) such as isoniazide 215 and ethionamide 216 are used as tuberculostatics, and of 2-benzylpyridine in the form of pheniramine 217 as antihistamine. 

The electron density map of pyridine (see IOC) clearly shows a high concentration of electron density (more red) on the nitrogen. Note that pyridine has been implicated in male sterility, although some claim this is a myth. Nonetheless, it is reasonable to exercise caution when pyridine is used. Several important pyridine derivatives have substituents on the aromatic ring, including 2,6-lutidine (11) and picolinic acid (12). Many derivatives of pyridine are found in pharmaceutically active compounds. One is nicotinic acid (niacin, 13), which is vitamin Bg and is found in liver, yeast, and meat. A deficiency in this vitamin can lead to pellagra (a wasting disease). Nicotinamide (14, niacinamide) is one of the two principal forms of the B-complex vitamin niacin. Nicotinamide may be useful for individuals with type 1 (insulin-dependent) diabetes. 

Heterocyclic compounds which contain a pyridine ring are frequently found in natural products. Accordingly, they are of special interest in pharmaceutical, agrochemical, and medicinal chemistry [117]. Also, a number of pyridine derivatives have been used in material chemistry [118]. Bipyridine groups are... 

Another important reaction of diketene derivatives is the Hant2sch pyridine synthesis (101). This synthesis is the preparation of 1,4-dihydropyridines (14) starting either from two acetoacetic esters, which react with an aldehyde and ammonia or a primary amine or from 3-aminocrotonates and 2-alkyhdene acetoacetic esters, both diketene derivatives. Several such dihydropyridines such as nifedipine [21829-25-4] (102), nimodipine [66085-59-4] and nicardipine [55985-32-5] exhibit interesting pharmaceutical activity as vasodilators (blood vessel dilation) and antihypertensives (see Cardiovascularagents). 

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