Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
Add more filters










Publication year range
1.
Bioorg Med Chem Lett ; 19(2): 428-32, 2009 Jan 15.
Article in English | MEDLINE | ID: mdl-19071020

ABSTRACT

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.


Subject(s)
Quinolines/pharmacology , Receptors, Serotonin, 5-HT1/drug effects , Administration, Oral , Animals , Biological Availability , Ligands , Quinolines/administration & dosage , Quinolines/chemistry , Quinolines/pharmacokinetics , Rats , Structure-Activity Relationship
2.
Bioorg Med Chem Lett ; 18(20): 5581-5, 2008 Oct 15.
Article in English | MEDLINE | ID: mdl-18829312

ABSTRACT

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.


Subject(s)
Chemistry, Pharmaceutical/methods , Selective Serotonin Reuptake Inhibitors/chemical synthesis , Serotonin 5-HT1 Receptor Antagonists , Administration, Oral , Animals , Chromatography/methods , Drug Design , Humans , Kinetics , Male , Models, Chemical , Molecular Conformation , Rats , Selective Serotonin Reuptake Inhibitors/pharmacology
3.
Chemistry ; 14(34): 10683-704, 2008.
Article in English | MEDLINE | ID: mdl-18821532

ABSTRACT

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.


Subject(s)
Insecticides/chemical synthesis , Limonins/chemical synthesis , Insecticides/chemistry , Limonins/chemistry , Molecular Conformation , Stereoisomerism
4.
J Med Chem ; 51(10): 2887-90, 2008 May 22.
Article in English | MEDLINE | ID: mdl-18433113

ABSTRACT

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.


Subject(s)
Piperazines/chemical synthesis , Quinolines/chemical synthesis , Serotonin 5-HT1 Receptor Antagonists , Animals , Blood-Brain Barrier/metabolism , Cerebral Cortex/metabolism , Humans , In Vitro Techniques , Piperazines/pharmacokinetics , Piperazines/pharmacology , Quinolines/pharmacokinetics , Quinolines/pharmacology , Radioligand Assay , Rats , Recombinant Proteins/pharmacology , Structure-Activity Relationship
5.
Bioorg Med Chem Lett ; 17(18): 5214-7, 2007 Sep 15.
Article in English | MEDLINE | ID: mdl-17629698

ABSTRACT

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.


Subject(s)
Receptors, Serotonin/metabolism , Serotonin Agents/metabolism , Administration, Oral , Biological Availability , Ligands , Serotonin Agents/pharmacokinetics
6.
Bioorg Med Chem Lett ; 17(4): 1033-6, 2007 Feb 15.
Article in English | MEDLINE | ID: mdl-17129726
8.
J Org Chem ; 70(25): 10615-8, 2005 Dec 09.
Article in English | MEDLINE | ID: mdl-16323886

ABSTRACT

[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.


Subject(s)
Ellipticines/chemical synthesis , Antineoplastic Agents/chemical synthesis , Carbazoles
10.
Bioorg Med Chem Lett ; 12(10): 1357-60, 2002 May 20.
Article in English | MEDLINE | ID: mdl-11992776

ABSTRACT

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.


Subject(s)
Piperazines/chemical synthesis , Receptors, Serotonin/metabolism , Serotonin Antagonists/chemical synthesis , Sulfonamides/chemical synthesis , Drug Design , Kinetics , Models, Molecular , Molecular Conformation , Piperazines/pharmacology , Receptors, Serotonin/drug effects , Serotonin Antagonists/pharmacology , Structure-Activity Relationship , Sulfonamides/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...