GABRA1 inhibitors(gamma-aminobutyric acid type A receptor subunit alpha1 inhibitors), GABRB2 inhibitors(gamma-aminobutyric acid type A receptor subunit beta2 inhibitors), GABRG2 inhibitors(gamma-aminobutyric acid type A receptor subunit gamma2 inhibitors)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Anxiety Disorders

Originator Organization

Pharmacia & Upjohn Co., Inc.

Active Organization-

Inactive Organization

Pharmacia & Upjohn Co., Inc.

License Organization-

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC18H15N5O2

InChIKeyKIGZWNHARYMTNM-UHFFFAOYSA-N

CAS Registry180989-85-9

100 Clinical Results associated with U-89267

100 Translational Medicine associated with U-89267

100 Patents (Medical) associated with U-89267

Literatures (Medical) associated with U-89267

01 Jan 1996·Journal of Medicinal ChemistryQ1 · MEDICINE

High-Affinity α-Aminobutyric Acid A/Benzodiazepine Ligands: Synthesis and Structure−Activity Relationship Studies of a New Series of Tetracyclic Imidazoquinoxalines

Q1 · MEDICINE

Article

Author: Tang, Andy H. ; Sethy, Vimala H. ; Mickelson, John W. ; Im, Wha Bin ; Petke, James D. ; Schreur, Peggy J. K. D. ; McGee, James E. ; Jacobsen, E. Jon ; Carter, Donald B. ; Im, Haesook K.

A series of tetracyclic imidazoquinoxaline analogs was developed which constrain the carbonyl group of the partial agonist 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-[(dimethylamino)carbonyl] - 4,5-dihydroimidazo[1,5-alpha]quinoxaline (2, U-91571) away from the benzene ring. These analogs orient the carbonyl group in the opposite direction of the previously reported full agonist 1-(5- cyclopropyl-1,2,4-oxadiazol-3-yl)-12,12a-dihydroimidazo[1,5- alpha]pyrrolo [2,1-c]quinoxalin-10(11H)-one (3, U-89267). A number of approaches were utilized to form the "bottom" ring of this tetracyclic ring system including intramolecular cyclizations promoted by Lewis acids or base, as well as metal-carbenoid conditions. The size and substitution pattern of the additional ring was widely varied. Analogs within this series had high affinity for the benzodiazepine receptor on the alpha-aminobutyric acid A chloride ion channel complex. From TBPS shift and Cl- current assays, the in vitro efficacy of compounds within this class ranged from antagonists to partial agonists with only 18a identified as a full agonist. Additionally, several analogs were quite potent at antagonizing metrazole-induced seizures indicating possible anticonvulsant or anxiolytic activity. Unlike 3, analogs in this series did not have high affinity for the diazepam insensitive alpha 6 beta 2 delta 2 subtype. These results suggest that either constraining the carbonyl group away from the benzene ring or the greater planarity that results from the additional cyclic structure provides analogs with partial agonist properties and prevents effective interaction with the alpha 6 beta 2 delta 2 subtype.

01 Mar 1994·Journal of Medicinal ChemistryQ1 · MEDICINE

Antagonist, Partial Agonist, and Full Agonist Imidazo[1,5-a]quinoxaline Amides and Carbamates Acting through the GABAA/Benzodiazepine Receptor

Q1 · MEDICINE

Article

Author: Sethy, Vimala H. ; Tang, Andrew H. ; Im, Wha B. ; Carter, Don B. ; TenBrink, Ruth E.

(4RS)-1-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)-12,12a-dihyd roimidazo[1,5- a]pyrrolo[2,1-c]quinoxalin-10(11H)-one (1a), 5-benzoyl-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4,5- dihydroimidazo[1,5-a]quinoxaline (13b), and tert-butyl (4S)-12,12a-dihydroimidazo[1,5-a]pyrrolo[2,1- c]quinoxaline-1-carboxylate (1e), as well as other imidazo[1,5-a]quinoxaline amides and carbamates, represent a new series of compounds which bind with high affinity to the GABAA/benzodiazepine receptor. These compounds exhibit a wide range of intrinsic efficacies as measured by [35S]TBPS binding ratios. The synthesis of 1a begins with the addition of DL-glutamic acid to 1-fluoro-2-nitrobenzene, followed by reduction of the nitro group and subsequent ring closure to form 3-(carbethoxymethyl)-1,2,3,4-tetrahydroquinoxalin-2-one, followed by a second ring closure to afford (4RS)-1,5-dioxo-1,2,3,4,5,6-hexahydropyrrolo[1,2-a]quinoxali ne as the key intermediate. Appendage of a substituted imidazo ring via the anion of 5-cyclopropyl-1,2,4-oxadiazol-3-yl gives 1a. The (-)- and (+)-isomers of 1a were prepared from 1-fluoro-2-nitrobenzene and L- and D-glutamic acid, respectively. 1a and its enantiomers demonstrated affinity for the [3H]flunitrazepam binding site with Ki's of 0.87, 0.62, and 0.65 nM, respectively.

100 Deals associated with U-89267

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Anxiety Disorders	Discovery	United States	Pharmacia & Upjohn Co., Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

U-89267

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation