Medicinal Chemistry
method can be used to identify the biotoxicface of the molecule (i.e., the toxicophore), which could then be engineered out of t ...
Oxidations of C-N systems Oxidation of C-S systems Oxidations of aldehyde and alcohol Aromatic hydroxylations Reductions Carbony ...
Oxidation: Aromatic Hydroxylation.Since many drugs contain aromatic rings, this is a very common metabolic transformation. The p ...
thus more readily excreted in the urine or bile. The enzymes that catalyze conjugations are transferases such as glucuronosyltra ...
used quite commonly). While cyclopropane may be reactive, due to ring strain, cyclopentane and cyclohexane are metabolically ine ...
Aldehydes and Ketones.Many metabolic routes are possible, including both oxidation and reduction. However, oxidations are more c ...
Thio Ethers. Thio ethers are commonly oxidized to a sulfoxide or sulfone. The conversion of chlorpromazine to chlorpromazine sul ...
Indole.This is a bicyclic (one five-membered ring plus one six-membered ring) aromatic heterocycle. Since most indole-containing ...
between 1.5 and 3.0; in accord with these requirements, the molecule should not be too polar, probably having no charged groups ...
Mask side effects or toxicity Improve the flavor of a drug An ester, for example, can be used to “mask” a carboxylate. Within ...
An ester group can be introduced into a local anesthetic, such as tolycaine (3.26), to prevent the drug from reaching the CNS if ...
Lipophilic groups that are not easily hydrolyzed are used extensively for depot preparations, which liberate the active drug mol ...
p-acetaminophenol. Another classical example of side-effect masking occurs in aspirin (3.34) and its many analogs — the result o ...
pilocarpine (2.2), used in the treatment of glaucoma, can be applied in a steady-release ocularinsert that lasts for a week. The ...
Mutagenic potential — effects on genetic stability of bacteria (Ames test) of mammalian cells in culture Carcinogenic potential ...
Phase 3 — the drug is studied in a large number of people (hundreds to thousands) who have the disease under study, typically us ...
that produce an adverse effect on the fetus. Toxicity problems have resulted in many drugs being withdrawn from the market, as s ...
molecule should be chemically unique, without evidence of previous pharmacological development. Selected References Designing a ...
P. Krogsgaard-Larsen, S. B. Christensen, H. Kofod (Eds.) (1984). Natural Products and Drug Development. Copenhagen: Munksgaard. ...
W. L. Jorgensen (2004). The many roles of computation in drug discovery. Science 303: 1813–1818. G. M. Keseru (2003). Structure/ ...
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