Halogenated drug derivatives

Niclosamide. This drug (6) is a halogenated salicylanilide derivative, C13H8Q2N204. 

Siuda, J.F., DeBemardis, J.F., Cavestri, R.C. Gas chromatographic detection of naturally occurring halogenated compounds derived from marine organisms. Food-Drugs from the sea. Marine Technol. Soc. Proc. 1972 [Worthen, L.R. (ed.)]... 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

The selectivity of the cyclization using enamino-esters 18-20 derived from m-halogenated anilines 14-16, provided mixtures of 5- and 7-substituted quinolines. In all of these cases, the cyclization gave either equal amounts of the 5- and 7- isomers or in the case of m-iodoaniline, about a 1 2 ratio was observed. During the time of these publications, it was the desire of the authors to obtain the 7-substituted quinolines, which were potential drugs for the treatment of malaria. 

Acylation of benzamidoxlme (144) with chloropropionyl chloride gives the 0-acylated derivative (145). Reaction of that intermediate with diethylamine serves first to cyclize the molecule to the 1,2,4-oxadiazole heterocycle subsequent displacement of the halogen on the side chain gives oxolamine (146),a drug with antltussive and spasmolytic activity. 

Okamoto et al [85] performed the optical resolution of primaquine and other racemic drugs by high performance liquid chromatography using cellulose and amylose tris-(phenylcarbamate) derivatives as chiral stationary phases. Primaquine and other compounds were effectively resolved by cellulose and/or amylose derivatives having substituents such as methyl, tertiary butyl, or halogen, on the phenyl groups. 

Trifluridine is also a halogenated derivative of timidin and is used for keratoconjuctivitis. hi tenns of action and region of use it is analogous to idoxuridine. It is also (like idoxuridine) turned into triphosphate, which inhibits DNA polymerase. A synonym of this drug is viroptic. 

Synthetic glucocorticoids are prednisolone, prednisone, methylprednisolone, dexamethasone, betamethasone and triamcinolone (Table 13.2). Hydrocortisone is available as either succinate or phosphate salts for oral and intravenous administration. It is the drug of choice when a rapid effect is required, e.g. acute adrenal insufficiency, or as peri-operative replacement therapy. Prednisolone can also be given intravenously. It has about 0.8 of the mineralocorticoid activity of hydrocortisone. Prednisone is a prodrug that is converted to prednisolone in the body. For chronic therapy, synthetic steroids without mineralocorticoid activity are preferred, such as dexamethasone, betamethasone or triamcinalone. Beclo-metasone passes membranes poorly and is more active topically than when given orally. It is used as an aerosol for chronic rhinitis and asthma, and topically in severe eczema. Fludrocortisone is a synthetic halogenated derivate of cortisol that is used for its mineralocorticoid effect. 

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