A search for new 5-HT1A/5-HT2A receptor ligands. In vitro and in vivo studies of 1-[omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones. 1998

M J Mokrosz, and B Duszyńska, and S Misztal, and A Kłodzińska, and E Tatarczyńska, and E Chojnacka-Wójcik, and M Dziedzicka-Wasylewska
Department of Medicinal Chemistry, Polish Academy of Sciences, Kraków, Poland.

A series of 1-¿omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2-14 was synthesized in order to obtain ligands with a dual 5-HT1A/5-HT2A activity. The majority of those compounds (2-5, 7, 10-13) exhibited a high 5-HT1A (Ki = 2-44 nM) and/or 5-HT2A affinity (Ki = 51 and 39 for 5 and 7, respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these effects evoked by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5-HT1A receptors. The 5-HT2A antagonistic activity was assessed by the blocking effect on the head twitches induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in mice. Two of the tested compounds, 1-¿3-[4-(3-chlorophenyl)-1-piperazinyl]propyl¿-6-fluoroindolin-2(1 H)-one (5) and 1-¿3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl¿indolin-2(1H)-one (7), demonstrated a high 5-HT1A/5-HT2A affinity and an in vivo antagonistic activity towards both receptor subtypes.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008297 Male Males
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
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
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D044263 Receptors, Serotonin, 5-HT1 A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels. Serotonin 5-HT1 Receptor,Serotonin Receptors, 5-HT1,5-HT1 Receptor,5-HT1 Receptors,Serotonin 5-HT1 Receptors,Serotonin, 5-HT1 Receptors,5 HT1 Receptor,5 HT1 Receptors,5-HT1 Receptor, Serotonin,5-HT1 Receptors Serotonin,5-HT1 Receptors, Serotonin,5-HT1 Serotonin Receptors,Receptor, 5-HT1,Receptor, Serotonin 5-HT1,Receptors Serotonin, 5-HT1,Receptors, 5-HT1,Receptors, 5-HT1 Serotonin,Receptors, Serotonin 5-HT1,Serotonin 5 HT1 Receptor,Serotonin 5 HT1 Receptors,Serotonin Receptors, 5 HT1,Serotonin, 5 HT1 Receptors
D044402 Receptor, Serotonin, 5-HT2A A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD. Serotonin 2A Receptor,5-HT(2A) Receptor,5-HT2A Receptor,Receptor, Serotonin 2A,Serotonin 2A Receptors,5 HT2A Receptor,Receptor, 5-HT2A,Receptors, Serotonin 2A
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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