Unknown

Dataset Information

0

Synthesis of chiral GABAA receptor subtype selective ligands as potential agents to treat schizophrenia as well as depression.

ABSTRACT: A series of novel imidazobenzodiazepine analogs of the lead chiral ligand SH-053-2'F-S-CH3 (2), an ?2/?3/?5 (Bz)GABA (A)ergic receptor subtype selective ligand, which reversed PCP-induced prepulse inhibition (PPI) of acoustic startle, were synthesized. These chiral (S)-CH3 ligands are targeted for the treatment of schizophrenia and depression. These new ligands were designed by modifying the liable ester functionality in 2 to improve the metabolic stability, cytotoxicity, and activity as compared to 2. Based on the data to date, the most promising ligands are the N-cyclopropyl amide GL-I-55 (8c) and the methyl bioisostere GL-I-65 (9a). The in vitro metabolic stability, cytotoxicity and in vivo locomotor effects are described in this report. Based on these results, 8c and 9a are the most promising for further in vivo pharmacology.

SUBMITTER: Li G 

PROVIDER: S-EPMC7413308 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Synthesis of chiral GABA<sub>A</sub> receptor subtype selective ligands as potential agents to treat schizophrenia as well as depression.

Li Guanguan G   Stephen Michael R MR   Kodali Revathi R   Zahn Nicolas M NM   Poe Michael M MM   Tiruveedhula V V N Phani Babu VVNPB   Huber Alec T AT   Schussman Melissa K MK   Qualmann Krista K   Panhans Cristina M CM   Raddatz Nicholas J NJ   Baker David A DA   Prevot Thomas D TD   Banasr Mounira M   Sibille Etienne E   Arnold Leggy A LA   Cook James M JM  

ARKIVOC : free online journal of organic chemistry 20180311 4

A series of novel imidazobenzodiazepine analogs of the lead chiral ligand SH-053-2'F-<i>S</i>-CH<sub>3</sub> (<b>2</b>), an α2/α3/α5 (Bz)GABA (A)ergic receptor subtype selective ligand, which reversed PCP-induced prepulse inhibition (PPI) of acoustic startle, were synthesized. These chiral (<i>S</i>)-CH<sub>3</sub> ligands are targeted for the treatment of schizophrenia and depression. These new ligands were designed by modifying the liable ester functionality in <b>2</b> to improve the metaboli  ...[more]

Similar Datasets

Unknown Improved Synthesis of Anxiolytic, Anticonvulsant and Antinociceptive ?2/?3-GABA(A)ergic Receptor Subtype Selective Ligands as Promising Agents to Treat Anxiety, Epilepsy, as well as Neuropathic Pain.
| S-EPMC7413181 | biostudies-literature
Unknown Development of GABAA Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments.
| S-EPMC4899155 | biostudies-literature
Unknown Structure-based evolution of subtype-selective neurotensin receptor ligands.
| S-EPMC4234217 | biostudies-literature
Other Stereoselective RNA Reaction with Chiral 2'-OH Acylating Agents
2023-11-14 | GSE247565 | GEO
Unknown Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAA Receptor Modulators.
| S-EPMC5497587 | biostudies-literature
Unknown Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.
| S-EPMC9345797 | biostudies-literature
Unknown Estrogen receptors alpha (ER?) and beta (ER?): subtype-selective ligands and clinical potential.
| S-EPMC4192010 | biostudies-other
Unknown Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression.
| S-EPMC5342919 | biostudies-literature
Unknown Triaryl-substituted Schiff bases are high-affinity subtype-selective ligands for the estrogen receptor.
| S-EPMC4002130 | biostudies-literature
Unknown What can crystal structures of aminergic receptors tell us about designing subtype-selective ligands?
| S-EPMC4279073 | biostudies-literature