John Maclean

Publications (3)7.95 Total impact

• Article: Structure-activity studies of a novel series of isoxazole-3-carboxamide derivatives as TRPV1 antagonists.

  Ronald Palin, Lynn Abernethy, Nasrin Ansari, Kenneth Cameron, Tom Clarkson, Maureen Dempster, David Dunn, Anna-Marie Easson, Darren Edwards, John Maclean, [......], Lesley-Anne Nisbet, Michael Ohlmeyer, Quynhchi Pham, Paul Ratcliffe, Yajing Rong, Andrew Roughton, Melanie Sammons, Robert Swanson, Heather Tracey, Glenn Walker
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  ABSTRACT: Optimisation of a screening hit incorporating both TRPV1 activity and solubility was conducted. Substitution of the isoxazole-3-carboxamide with the bespoke 1S, 3R-3-aminocyclohexanol motif afforded the requisite balance of potency and solubility. Compounds 32 and 40 were found to have antihyperalgesic effects in the rat CFA Hg assay and induce a mechanism based hyperthermia.
  Bioorganic & medicinal chemistry letters 02/2011; 21(3):892-8. · 2.65 Impact Factor
• Article: Discovery of potent, soluble and orally active TRPV1 antagonists. Structure-activity relationships of a series of isoxazoles.

  Paul Ratcliffe, Lynn Abernethy, Nasrin Ansari, Ken Cameron, Tom Clarkson, Maureen Dempster, David Dunn, Anna-Marie Easson, Darren Edwards, Katy Everett, [......], Lesley-Anne Nisbet, Michael Ohlmeyer, Ronnie Palin, Quynhchi Pham, Yajing Rong, Andrew Roughton, Melanie Sammons, Robert Swanson, Heather Tracey, Glenn Walker
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  ABSTRACT: Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration.
  Bioorganic & medicinal chemistry letters 01/2011; 21(15):4652-7. · 2.65 Impact Factor
• Article: Identification of potent, soluble, and orally active TRPV1 antagonists.

  Paul Ratcliffe, John Maclean, Lynn Abernethy, Tom Clarkson, Maureen Dempster, Anna-Marie Easson, Darren Edwards, Katy Everett, Helen Feilden, Peter Littlewood, Duncan McArthur, Deborah McGregor, Hazel McLuskey, Olaf Nimz, Lesley-Anne Nisbet, Ronnie Palin, Heather Tracey, Glenn Walker
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  ABSTRACT: Optimization of a water soluble, moderately potent lead series of isoxazole-3-carboxamides was conducted, affording a compound with the requisite balance of potency, solubility and physicochemical properties for in vivo use. Compound 8e was demonstrated to be efficacious in a rat model of inflammatory pain, following oral administration.
  Bioorganic & medicinal chemistry letters 01/2011; 21(8):2559-63. · 2.65 Impact Factor