Publications by authors named "Peter J Lovell"

10 Publications

  • Page 1 of 1

Studies on a series of potent, orally bioavailable, 5-HT(1) receptor ligands--part II.

Bioorg Med Chem Lett 2009 Jan 19;19(2):428-32. Epub 2008 Nov 19.

Neuroscience Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.

A series of 5-(piperidinylethyloxy)quinoline 5-HT(1) receptor ligands have been studied by elaboration of the series of dual 5-HT(1)-SSRIs reported previously. These new compounds display a different in vitro pharmacological profile with potent affinity across the 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors and selectivity against the serotonin transporter. Furthermore, they have improved pharmacokinetic profiles and CNS penetration.
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http://dx.doi.org/10.1016/j.bmcl.2008.11.052DOI Listing
January 2009

Novel 5-HT(1A/1B/1D) receptors antagonists with potent 5-HT reuptake inhibitory activity.

Bioorg Med Chem Lett 2008 Oct 3;18(20):5581-5. Epub 2008 Sep 3.

Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.

Novel 2-methyl-5-quinolinyl-1-piperazinylalkyl-3,4-dihydro-2H-1,4-benzoxazin-3-ones showing high affinities for the 5-HT(1A/1B/1D) receptors coupled with potent 5-HT reuptake inhibitory activity have been discovered. This is the first report describing docking of the lead compound 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-2H-1,4-benzoxazin-3(4H)-one 1, into a model of the 5-HT transporter and the 5-HT(1A) receptor model.
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http://dx.doi.org/10.1016/j.bmcl.2008.08.110DOI Listing
October 2008

The synthesis of azadirachtin: a potent insect antifeedant.

Chemistry 2008 ;14(34):10683-704

Department of Chemistry, University of Cambridge, UK.

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.
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http://dx.doi.org/10.1002/chem.200801103DOI Listing
December 2008

Discovery of potent, orally bioavailable, selective 5-HT1A/B/D receptor antagonists.

J Med Chem 2008 May 24;51(10):2887-90. Epub 2008 Apr 24.

Psychiatry Centre of Excellence for Drug Discovery and Molecular Discovery Research, GlaxoSmithKline, Essex, UK.

5-HT1 receptor antagonists have been discovered with good selectivity over the 5-HT transporter. This is the first report of highly potent, selective ligands for the 5-HT1A/B/D receptors with low intrinsic activity, which represent a useful set of molecules for further understanding the roles of the 5-HT1 receptor subtypes and providing new approaches for the treatment of depression.
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http://dx.doi.org/10.1021/jm8001444DOI Listing
May 2008

Studies on a series of potent, orally bioavailable, 5-HT(1) receptor ligands.

Bioorg Med Chem Lett 2007 Sep 30;17(18):5214-7. Epub 2007 Jun 30.

Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.

A series of 5-(piperidinylethyloxy)quinoline 5-HT(1) receptor ligands have been studied by elaboration of the series of dual 5-HT(1)-SSRIs reported previously. These new compounds display a different pharmacological profile with potent affinity across the 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors and selectivity against the serotonin transporter. Furthermore, they have improved pharmacokinetic profiles and CNS penetration.
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http://dx.doi.org/10.1016/j.bmcl.2007.06.078DOI Listing
September 2007

3,4-Dihydro-2H-benzoxazinones as dual-acting 5-HT1A receptor antagonists and serotonin reuptake inhibitors.

Bioorg Med Chem Lett 2007 Feb 15;17(4):1033-6. Epub 2006 Nov 15.

Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.

Investigation of halogen substitution in lead compound 1 has led to the identification of analogues which combine high affinity for 5-HT(1A) receptors and potent serotonin reuptake inhibitory activity. Several compounds show an improved selectivity over 5-HT(1B) and 5-HT(1D) receptors and a superior pharmacokinetic profile in the rat.
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http://dx.doi.org/10.1016/j.bmcl.2006.11.031DOI Listing
February 2007

Synthesis of ellipticine: a radical cascade protocol to aryl- and heteroaryl-annulated[b]carbazoles.

J Org Chem 2005 Dec;70(25):10615-8

Department of Chemistry, Loughborough University, Loughborough, Leics. LE11 3TU, Great Britain.

[reaction: see text] Imidoyl selanides, synthesized from amides, have been used as radical precursors of imidoyl radicals in cascade reactions. The novel radical cascade has been developed for the simple synthesis of the medicinally important aryl-annulated[b]carbazoles. The protocol has been exemplified with the high-yielding total synthesis of the anticancer alkaloid ellipticine.
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http://dx.doi.org/10.1021/jo0519920DOI Listing
December 2005

The identification of potent and selective imidazole-based inhibitors of B-Raf kinase.

Bioorg Med Chem Lett 2006 Jan 2;16(2):378-81. Epub 2005 Nov 2.

Department of Medicinal Chemistry, Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.

A novel triarylimidazole derivative, SB-590885 (33), bearing a 2,3-dihydro-1H-inden-1-one oxime substituent has been identified as a potent and extremely selective inhibitor of B-Raf kinase.
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http://dx.doi.org/10.1016/j.bmcl.2005.09.072DOI Listing
January 2006

A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists.

Bioorg Med Chem Lett 2005 Nov;15(22):4989-93

Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithkline Pharmaceuticals, Third Avenue, Harlow, Essex CM19 5AW, UK.

Bisaryl cyclic ureas have been identified as high affinity 5-HT2C receptor antagonists with selectivity over 5-HT2A and 5-HT2B. Compounds such as 8 and 22 have shown oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function in rodents.
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http://dx.doi.org/10.1016/j.bmcl.2005.08.004DOI Listing
November 2005

Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor antagonists.

Bioorg Med Chem Lett 2002 May;12(10):1357-60

Department of Psychiatry, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.

The synthesis of novel 3-(octahydropyrido[1,2-a]pyrazin-2-yl)- and 3-(hexahydropyrrolo[1,2-a]pyrazin-2-yl)phenyl-2-benzo[b]thiophene sulphonamide derivatives 3, (S)-4 and (R)-4 is described. The compounds show high affinity for the 5-HT6 receptor, excellent selectivity against a range of other receptors and good brain penetration.
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http://dx.doi.org/10.1016/s0960-894x(02)00172-5DOI Listing
May 2002