Search Results - "Showell, Graham A"

Exploitation of silicon medicinal chemistry in drug discovery by Mills, John S, Showell, Graham A

“…There remains considerable pressure on the pharmaceutical industry to increase productivity and reduce the attrition of drug candidates. Genomics, parallel…”
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Trimethylsilylpyrazoles as novel inhibitors of p38 MAP kinase: A new use of silicon bioisosteres in medicinal chemistry by Barnes, Matthew J., Conroy, Richard, Miller, David J., Mills, John S., Montana, John G., Pooni, Parminder K., Showell, Graham A., Walsh, Louise M., Warneck, Julie B.H.

“…The synthesis, physicochemical properties and pharmacological profiles of two novel silicon-containing p38 MAP kinase inhibitors are described. The synthesis,…”
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Chemistry challenges in lead optimization: silicon isosteres in drug discovery by Showell, Graham A, Mills, John S

“…During the lead optimization phase of drug discovery projects, the factors contributing to subsequent failure might include poor portfolio decision-making and…”
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Sila-venlafaxine, a Sila-Analogue of the Serotonin/Noradrenaline Reuptake Inhibitor Venlafaxine:  Synthesis, Crystal Structure Analysis, and Pharmacological Characterization by Daiss, Jürgen O, Burschka, Christian, Mills, John S, Montana, John G, Showell, Graham A, Warneck, Julie B. H, Tacke, Reinhold

“…The serotonin/noradrenaline reuptake inhibitor rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol (rac-venlafaxine, rac-1a) is in clinical use…”
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Synthesis, Crystal Structure Analysis, and Pharmacological Characterization of Disila-bexarotene, a Disila-Analogue of the RXR-Selective Retinoid Agonist Bexarotene by Daiss, Jürgen O, Burschka, Christian, Mills, John S, Montana, John G, Showell, Graham A, Fleming, Ian, Gaudon, Claudine, Ivanova, Diana, Gronemeyer, Hinrich, Tacke, Reinhold

“…Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the RXR-selective retinoid agonist bexarotene (1a)…”
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Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors by Street, Leslie J, Baker, Raymond, Book, Tracey, Kneen, Clare O, MacLeod, Angus M, Merchant, Kevin J, Showell, Graham A, Saunders, John, Herbert, Richard H

“…The synthesis and biochemical evaluation of novel 1,2,4-oxadiazole-based muscarinic agonists which can readily penetrate into the CNS is reported. Efficacy and…”
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( R)-Sila-venlafaxine: A selective noradrenaline reuptake inhibitor for the treatment of emesis by Showell, Graham A., Barnes, Matthew J., Daiss, Jürgen O., Mills, John S., Montana, John G., Tacke, Reinhold, Warneck, Julie B.H.

“…The in vitro profile and in vivo anti-emetic activity of the selective noradrenaline reuptake inhibitor ( R )- 2 are reported. Sila-substitution of drugs (the…”
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Silicon Analogues of the Nonpeptidic GnRH Antagonist AG-045572: Syntheses, Crystal Structure Analyses, and Pharmacological Characterization by Barnes, Matthew J., Burschka, Christian, Büttner, Matthias W., Conroy, Richard, Daiss, Jürgen O., Gray, Ian C., Hendrick, Alan G., Tam, L. H., Kuehn, Diana, Miller, David J., Mills, John S., Mitchell, Philip, Montana, John G., Muniandy, Parameswary A., Rapley, Helen, Showell, Graham A., Tebbe, David, Tacke, Reinhold, Warneck, Julie B. H., Zhu, Bin

“…AG‐045572 (CMPD1, 1 a) is a nonpeptidic gonadotropin‐releasing hormone (GnRH) antagonist that has been investigated for the treatment of sex hormone‐related…”
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The design of a new potent and selective ligand for the orphan bombesin receptor subtype 3 (BRS3) by Boyle, Robert G., Humphries, John, Mitchell, Tim, Showell, Graham A., Apaya, Robert, Iijima, Hiroaki, Shimada, Hiroshi, Arai, Tomonori, Ueno, Hiroaki, Usui, Yoshihiro, Sakaki, Toshiro, Wada, Etsuko, Wada, Keiji

“…Extensive SAR studies on the unselective BRS3 agonist, [H‐D‐Phe6,β‐Ala11,Phe13,Nle14]‐bombesin‐(6‐14)‐nonapeptide amide, have highlighted structural features…”
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Synthesis and antihypertensive activity of 6,7-disubstituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols by Evans, John M, Fake, Charles S, Hamilton, Thomas C, Poyser, Robert H, Showell, Graham A

“…A series of novel 6,7-disubstituted trans-3,4-dihydro-2, 2-dimethyl-4-pyrrolidino-(or piperidino)-2H-1-benzopyran-3-ols was prepared and tested for…”
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High-Affinity and Potent, Water-Soluble 5-Amino-1,4-benzodiazepine CCKB/Gastrin Receptor Antagonists Containing a Cationic Solubilizing Group by Showell, Graham A, Bourrain, Sylvie, Neduvelil, Joseph G, Fletcher, Stephen R, Baker, Raymond, Watt, Alan P, Fletcher, Alan E, Freedman, Stephen B, Kemp, John A

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Thyroid hormone analogs. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart by Leeson, Paul D, Ellis, David, Emmett, John C, Shah, Virendra P, Showell, Graham A, Underwood, Anthony H

“…Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a…”
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Synthesis and in vitro biological profile of all four isomers of the potent muscarinic agonist 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane by Showell, Graham A, Baker, Raymond, Davis, Juliet, Hargreaves, Richard, Freedman, Stephen B, Hoogsteen, Karst, Patel, Shailendra, Snow, Roger J

“…The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained…”
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Selective thyromimetics. Cardiac-sparing thyroid hormone analogs containing 3'-arylmethyl substituents by Leeson, Paul D, Emmett, John C, Shah, Virendra P, Showell, Graham A, Novelli, Ricardo, Prain, H. Douglas, Benson, Martin G, Ellis, David, Pearce, Nigel J, Underwood, Anthony H

“…Introduction of specific arylmethyl groups at the 3'-position of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3), and its known hormonally active…”
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Synthesis and characterization of all four isomers of the muscarinic agonist, 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] by Saunders, John, Showell, Graham A, Baker, Raymond, Freedman, Stephen B, Hill, David, McKnight, Alexander, Newberry, Nigel, Salamone, John D, Hirshfield, Jordan, Springer, James P

“…The four separated isomers of the muscarinic agonist 1, previously known as AF30, have been synthesized by a route that has allowed the absolute…”
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Tetrahydropyridyloxadiazoles: semi-rigid muscarinic ligands by Showell, Graham A, Gibbons, Tracey L, Kneen, Clare O, MacLeod, Angus M, Merchant, Kevin, Saunders, John, Freedman, Stephen B, Patel, Shailendra, Baker, Raymond

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2-Methyl-1,3-dioxaazaspiro[4.5]decanes as novel muscarinic cholinergic agonists by Saunders, John, Showell, Graham A, Snow, Roger J, Baker, Raymond, Harley, Elizabeth A, Freedman, Stephen B

“…Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30)…”
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Synthesis, crystal structure analysis, and pharmacological characterization of desmethoxy-sila-venlafaxine, a derivative of the serotonin/noradrenaline reuptake inhibitor sila-venlafaxine by Daiß, Jürgen O., Burschka, Christian, Mills, John S., Montana, John G., Showell, Graham A., Warneck, Julie B.H., Tacke, Reinhold

“…The syntheses and crystal structure analyses of rac-desmethoxy-sila-venlafaxine ( rac- 3) and its hydrochloride rac- 3 · HCl are reported. Compound rac- 3 is a…”
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Binding of 2,4-disubstituted morpholines at human D 4 dopamine receptors by Showell, Graham A., Emms, Frances, Marwood, Rosemarie, O'Connor, Desmond, Patel, Smita, Leeson, Paul D.

“…The synthesis of a series of 2,4-disubstituted morpholines is described and their affinities at human dopamine receptors reported. The orally bioavailable…”
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Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor by Bourrain, S, Collins, I, Neduvelil, J G, Rowley, M, Leeson, P D, Patel, S, Emms, F, Marwood, R, Chapman, K L, Fletcher, A E, Showell, G A

“…Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I…”
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