Drug analogs

R. H. Abeles, Enzyme Inhibitors Ground State/ Transition-State Analogs , Drug, Dev. Res. 1987, 10, 221-234. 

Obach RS. Mechanism of cytochrome P4503A4- and 2D6-catalyzed dehydrogenation of ezlopitant as probed with isotope effects using five deuterated analogs. Drug Metab Dispos 2001 29(12) 1599-1607. 

M. R. Brzezinski, B. J. Spink, R. A. Dean, C. E. Berkman, J. R. Cashman, W. F. Bosron, Human Liver Carboxylesterase hCE-1 Binding Specificity for Cocaine, Heroin, and Their Metabobtes and Analogs , Drug Metab. Dispos. 1997, 25, 1089-1096. 

Traditionally, lead compounds have been discovered in one of two ways. The hrst is one of trial and error. This is the way many plant and animal products and minerals have been found to be effective in the treatment of some medical disorder. For example, no one knows when the hrst person learned that chewing on the bark of the willow tree [Salix alba) helped relieve pain and reduce fever, but willow bark has been used in many cultures for untold centuries for just that purpose. Today we know that the active ingredient in willow bark is a derivative of salicylic acid (CgH4(OH)COOH), which today is sold commercially as aspirin or one of its analogs. Drug researchers continue to rely heavily on the study of folk medicines—a science known as ethnopharmacology—for the discovery of new plant and animal products that may have medical applications in the modern world. Indeed, scientists have discovered that the medical... 

A second hypothesis to explain the cardiovascular effects of clonidine involves an interaction with imidazoline-1 receptors (Bousquet and Feldman 1999). However, the available evidence at present does not prove conclusively the imidazoline hypothesis for the mechanism of action of clonidine and analog drugs, like rilmeni-dine and moxonidine (Szabo 2002). 

Presynaptic 5-HTid inhitory heteroreceptors exist on substance P- and CGRP-containing terminals (Smith et al. 2002 Hou et al. 2001 Table 2). Activation of these receptors by agonists like sumatriptan and related analogs leads to inhibition of the release of these two neurotransmitters (Williamson et al. 1997, 2001). The therapeutic efficacy of sumatriptan and analogous drugs in the treatment of... 

Reid G, Wielinga P, Zelcer N, et al. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol Pharmacol 2003 63 1094-1103. 

Takenaga, N., Ishii, M., and Kamei, T., Structure-activity relationship in O-glucuronidation of indolocarbazole analogs, Drug Metab. Disposition, 30, 494-497, 2002. 

The recent determination of the crystal structure of a ternary catalytic complex of HW-1 RT with a substrate (dTTP) and the DNA-primer and template [121] (Fig. 8) has provided the structured basis of resistance it has been found that most mutations causing resistemce to nucleoside-analog drugs are located closely to the nucleoside binding site. 

Leung S, Bendayan R. Role of P-glycoprotein in the renal transport of dideox3mucleoside analog drugs. Can J Physiol Pharmacol 1999 77(8) 625-630. 

Thymidine kinase (TK) is an essential enzyme for phosphorylation of deoxy-thymidine and DNA synthesis. In addition, it is the enzyme responsible for activation and-or metabolism of a variety of nucleoside analog drugs (for example DNA chain terminators such as AZT). This enzyme has received significant interest for treatment of herpes simplex virus infections (cf. acyclovir) or mycobacterium infections. In both cases, therapies have been developed that seek to exploit the differences between viral or bacterial TK and human TK. Two forms of thymidine kinase are found in human cells TK1 (cytosolic, active in replicating cells) and TK2 (mitochondrial, constitutively active). Some antiviral-anticancer drugs are metabolized by either one of the isozymes. In some cases, this may be associated with either lack of efficacy or... 

Nicolaou, K., Smith, J. and Lefer, A. (1982). Chemistry and pharmacology of a series of new thromboxane analogs. Drugs Future, 7, 331-340... 

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