Download Analogue-based Drug Discovery by Janos Fischer, C. Robin Ganellin, David P. Rotella PDF

By Janos Fischer, C. Robin Ganellin, David P. Rotella

The 1st authoritative review of earlier and present concepts for profitable drug improvement via analog new release, this targeted source spans all vital drug periods and all significant healing fields, together with histamine antagonists, ACE inhibitors, beta blockers, opioids, quinolone antibiotics, steroids and anticancer platinum compounds.Of the nineteen analog periods provided intimately, nine are defined by way of the scientists who discoverd them.The publication encompasses a desk of the main profitable drug analogs as in line with the IMS score and compares them by way of chemical constitution, mode of motion and patentability.

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In 2001, the antimalarial drug quinacrine and the antipsychotic drug chlorpromazine (Fig. 14) were shown to inhibit prion infection in cells. Prusiner and coworkers [24] identified the drugs independently, and found that they inhibited the conversion of normal prion protein into infectious prions, and also cleared prions from infected cells. Both drugs can cross over from the bloodstream to the brain, where the prion diseases are localized. CH3 N N HN Cl MeO N quinacrine Cl N S chlorpromazine Fig.

Natl. Acad. Sci. USA, 2001, 98, 9836–9841. 25 Terret NK, Bell AS, Brown D, Ellis P. Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg. Med. Chem. , 1996, 6, 1819–1824. 26 Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IHC. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treat- ment of penile erectile dysfunction. Int.

10 Cholinergic twin drugs. Other examples of twin drugs are the antioxidant probucol, which lowers the cholesterol level in blood, and cromolyn, a chromone heterocycle, which is useful in the inhalational treatment of bronchial asthma (Fig. 11). S HO2C S HO O O CO2H OH OH O probucol O O O cromolyn Fig. 11 Probucol and cromolyn are also twin drugs. 2 The Pros and Cons of Analogue Design The usual objectives of analogue design are the identification and development of a possibly improved version of a prototype drug.

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