Analogue development

RJ Linhardt, T Toida. Heparin Oligosaccharides New Analogues Development and Applications. In ZJ Witczak, KA Nieforth. Carbohydrate as Drugs. New York Marcel Dekker, 1997, pp 277-341. 

Davis (1989, 332-33) also argues that neither the HERP index nor, implicitly, an analogue developed from the TI rather than the TD50 measure can account for... 

Seven patients using different topical prostaglandin F2a analogues developed bilateral poliosis, which appeared at 1.5-6 months after the start of therapy (17). Four used latanoprost, two used bimatoprost, and one used travaprost... 

An additional family of organometallic materials is the cyanometallates, which are Prussian blue analogues. These are microporous materials, similar to zeolites, with relatively large adsorption space and small access windows [237-241], These Prussian blue analogues develop zeolite-like structures based upon a simple cubic (T[M(CN)6]) framework, in which octahedral [M(CN)6]" complexes are linked via octahedrally coordinated, nitrogen-bound Tm+ ions [237], In the prototypic compound, that is, Prussian blue, specifically (Fe4[Fe(CN)6]3 14H20), charge balance with the Fe3+ ions conducts to vacancies at one-quarter of the [Fe(CN)6]4 complexes [242],... 

More effective is the chiral borohydride analogue developed by Corey, Bakshi, and Shibita. It is based upon a stable boron heterocycle made from an amino alcohol derived from proline, and is known as the CBS reagent after its developers. 

Figure 16.9 Electrical circuit analogue developed to account for the influence of two Shockley-Read-Hall electronic transitions through deep-level states. See the discussion of Figure 12.8.

Katoch-Rouse R, Pavlova OA, Caulder T, Hoffman AF, Mukhin AG, Horti AG (2003) Synthesis, structure-activity relationship, and evaluation of SR141716 analogues development of central cannabinoid receptor ligands with lower lipophUicity. J Med Chem 46 642-645... 

The article by Miyake (Kawasaki), Maeda (Tokyo), and this writer details the long career of Sumio Umezawa devoted to the chemistry and medicinal applications of antibiotics, especially the aminocycUtols (aminoglycosides), afield dominated by Sumio and his microbiologist/biochemist brother Hamao from the earliest days of streptomycin through to practical semisynthetic analogues developed by Sumio that have enjoyed wide clinical application. The complementary articles by the two Umezawa brothers in Volume 30 of this series remain a definitive reference work on these antibiotics. 

Epibatidine (9.48) is a potent analgesic from the Ecuadorian poison frog Epipedobates tricolor,408 Although the compound itself is too toxic to use as a drug, an analogue developed by Abbott Laboratories (9.49) is less toxic, nonaddictive, and as effective as morphine.409... 

Numerous podophyllotoxin analogues have been prepared in attempts to develop improved drugs and the three new derivatives GL-331 (11), NK 611 (12), and TOP-53 (13) illustrate some of the leading candidates to emerge from this work. The development of these and other podophyllotoxin analogues has been reviewed. In spite of extensive synthetic work, the natural product podophyllotoxin remains the preferred source of all the analogues developed to date. 

The case of hypercalcaemia with the use of a topical vitamin D analogue is rare and the strength of the preparation of tacalcitol used was fivefold higher than the current licensed preparation of 4 micrograms/g (Curato-derm). However, bear this case in mind should a patient taking thiazides with a topical vitamin D analogue develop hypercalcaemia. 

Scheme 23.8 Gram-scale synthesis of Ramipril analogues developed by Feng and coworkers. ...

A large number of ansamacrolides, exemplified by maytansine, 8, have potent antitumor activity. Maytansine has been subjected to clinical studies in the NCI program and has been disappointing as an anticancer agent. Furthermore, it has been shown to be quite toxic. Analogue development may produce a more useful and less toxic antitumor agent in the future (881). 

The intensive program of analogue synthesis initiated after the discovery of cisplatin has led to clinical trials for a number of second-generation complexes. Again it should be emphasized that analogue development in general has been responsible for many compounds of clinical usefulness and their study contributes to our better understanding of the parent complex. 

Figure 41.7 Chiral 4-pyrrolidinopyridine analogues developed by Kawabata et al. (Cbz = benzyloxycarbonyl).

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