BIOMAT Database Logo BIOMAT Database Logo

3,4-Dihydro-3-amino-2H-1-benzopyran derivatives as 5-HT1A receptor ligands and potential anxiolytic agents. 1. Synthesis and structure--activity relationship studies. 1994

T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Laboratoire de Chimie Bioorganique et Analytique, associé au CNRS, Université d'Orléans, France.

A series of 3,4-dihydro-3-amino-2H-1-benzopyran derivatives were prepared in order to determine the necessary structural requirements for good affinity for 5-HT1A receptors and high selectivity versus other receptors. Modifications of the extracyclic amino substituents, the length of the alkyl side chains, and their substituents were explored. The best compounds (9g, 9k, 15b, 15d) possess imido or sulfonamido functional groups with a preferential length of four methylenes for the side chain. After resolution, the dextrorotatory enantiomers showed better affinity and selectivity for 5-HT1A receptors. These compounds have been proven to be full agonists. 9g and its enantiomers showed anxiolytic activity in vivo in various comportemental models. The compound (+)-9g is currently under clinical investigation.

UI MeSH Term Description Entries
D010856 Columbidae Family in the order COLUMBIFORMES, comprised of pigeons or doves. They are BIRDS with short legs, stout bodies, small heads, and slender bills. Some sources call the smaller species doves and the larger pigeons, but the names are interchangeable. Columba livia,Doves,Pigeons,Domestic Pigeons,Feral Pigeons,Rock Doves,Rock Pigeons,Domestic Pigeon,Dove,Dove, Rock,Doves, Rock,Feral Pigeon,Pigeon,Pigeon, Domestic,Pigeon, Feral,Pigeon, Rock,Pigeons, Domestic,Pigeons, Feral,Pigeons, Rock,Rock Dove,Rock Pigeon
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
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
D001578 Benzopyrans Compounds with a core of fused benzo-pyran rings. Benzopyran,Chromene,Chromenes
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
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
D014151 Anti-Anxiety Agents Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. Anti-Anxiety Agent,Anti-Anxiety Drug,Anxiolytic,Anxiolytic Agent,Anxiolytic Agents,Tranquilizing Agents, Minor,Anti-Anxiety Drugs,Anti-Anxiety Effect,Anti-Anxiety Effects,Antianxiety Effect,Antianxiety Effects,Anxiolytic Effect,Anxiolytic Effects,Anxiolytics,Tranquillizing Agents, Minor,Agent, Anti-Anxiety,Agent, Anxiolytic,Agents, Anti-Anxiety,Agents, Anxiolytic,Agents, Minor Tranquilizing,Agents, Minor Tranquillizing,Anti Anxiety Agent,Anti Anxiety Agents,Anti Anxiety Drug,Anti Anxiety Drugs,Anti Anxiety Effect,Anti Anxiety Effects,Drug, Anti-Anxiety,Drugs, Anti-Anxiety,Effect, Anti-Anxiety,Effect, Antianxiety,Effect, Anxiolytic,Effects, Anti-Anxiety,Effects, Antianxiety,Effects, Anxiolytic,Minor Tranquilizing Agents,Minor Tranquillizing Agents
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

Related Publications

T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Synthesis of novel 5-substituted 3-amino-3,4-dihydro-2H-1-benzopyran derivatives and their interactions with the 5-HT1A receptor.
July 2000, Journal of medicinal chemistry,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
5-substituted 3,4-dihydro-3-amino-2H-1-benzopyran derivatives: synthesis and interaction with serotoninergic receptors.
July 2001, The Journal of pharmacy and pharmacology,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies.
July 1988, Journal of medicinal chemistry,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Synthesis and antihypertensive activity of substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols.
November 1983, Journal of medicinal chemistry,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Potential antihypertensive agents. 3. 3,4-Dihydro-2H-1,4-benzothiazine derivatives.
March 1969, Journal of medicinal chemistry,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Design, synthesis and structure-activity relationship studies of 6-phenyl-4,5-dihydro-3(2H)-pyridazinone derivatives as cardiotonic agents.
January 2008, Arzneimittel-Forschung,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Synthesis and antihypertensive activity of 6,7-disubstituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols.
September 1984, Journal of medicinal chemistry,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Novel potassium channel activators: synthesis and structure-activity relationship studies of 3,4-dihydro-2H-1,4-benzoxazine derivatives.
January 1996, Chemical & pharmaceutical bulletin,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Structure-activity relationship studies of CNS agents. XII. 1-[4-(4-aryl-1-piperazinyl)butyl]-3,4-dihydro-2(1H)-quinolinones: new 5-HT1A, 5-HT2 and D2 ligands with a potential antipsychotic activity.
April 1994, Drug design and discovery,
T Podona, and B Guardiola-Lemaître, and D H Caignard, and G Adam, and B Pfeiffer, and P Renard, and G Guillaumet
Synthesis and selective coronary vasodilatory activity of 3,4-dihydro-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol derivatives: novel potassium channel openers.
September 1996, Journal of medicinal chemistry,
Copied contents to your clipboard!