Biomaterial Database

Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha(2)-adrenoceptor antagonistic activities: a novel series of potential antidepressants. 2003

J Ignacio Andrés, and Jesús Alcázar, and José M Alonso, and Rosa M Alvarez, and José M Cid, and Ana I De Lucas, and Javier Fernández, and Sonia Martínez, and Carmen Nieto, and Joaquín Pastor, and Margot H Bakker, and Ilse Biesmans, and Lieve I Heylen, and Anton A Megens

Johnson & Johnson Pharmaceutical Research & Development, Medicinal Chemistry Department, Jarama s/n, 45007 Toledo, Spain. iandres@prdes.jnj.com

The synthesis of a series of novel 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles as novel dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists is described. Their affinity at the three different human alpha(2)-adrenoceptor subtypes and the 5-HT transporter site is reported. The in vivo activity of the compounds was measured in two different assays: (1). inhibition of pCA-induced excitation, which evaluates the ability to block the central 5-HT transporter, and (2). inhibition of xylazine-induced loss of righting, which evaluates the ability to block central alpha(2)-adrenoceptors.

UI	MeSH Term	Description	Entries
D007555	Isoxazoles	Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.	Isoxazole
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D000317	Adrenergic alpha-Antagonists	Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.	Adrenergic alpha-Receptor Blockaders,alpha-Adrenergic Blocking Agents,alpha-Adrenergic Receptor Blockaders,alpha-Blockers, Adrenergic,Adrenergic alpha-Blockers,alpha-Adrenergic Antagonists,alpha-Adrenergic Blockers,Adrenergic alpha Antagonists,Adrenergic alpha Blockers,Adrenergic alpha Receptor Blockaders,Agents, alpha-Adrenergic Blocking,Antagonists, alpha-Adrenergic,Blockaders, Adrenergic alpha-Receptor,Blockaders, alpha-Adrenergic Receptor,Blockers, alpha-Adrenergic,Blocking Agents, alpha-Adrenergic,Receptor Blockaders, alpha-Adrenergic,alpha Adrenergic Antagonists,alpha Adrenergic Blockers,alpha Adrenergic Blocking Agents,alpha Adrenergic Receptor Blockaders,alpha Blockers, Adrenergic,alpha-Antagonists, Adrenergic,alpha-Receptor Blockaders, Adrenergic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000928	Antidepressive Agents	Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.	Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014991	Xylazine	An adrenergic alpha-2 agonist used as a sedative, analgesic and centrally acting muscle relaxant in VETERINARY MEDICINE.	BAY-Va 1470,Rompun,Xylaxine,Xylazin,Xylazine Hydrochloride,Xylazine Monohydrochloride,Xylazine Phosphate (1:1),BAY Va 1470,BAYVa 1470