The potencies for in vivo inhibition of substantia nigra pars compacta dopamine single cell firing were determined for apomorphine, BHT 920, N-0923, (+/-)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), (+)-3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), pramipexole, quinelorane, quinpirole, RU 24926, U-86170, and U-91356. Significant correlation was obtained between the potencies of these 11 highly efficacious dopamine receptor agonists and the in vitro binding affinities at dopamine D3 receptors, but not at dopamine D2L receptors. These results support a functional role for the dopamine D3 receptor subtype in the autoreceptor-mediated regulation of dopamine cell activity, while a role for dopamine D2 receptors awaits further analysis. In addition, the results demonstrate the limitations of using currently available dopamine receptor agonists to delineate relative in vivo roles for the dopamine D2 and D3 receptor subtypes.

Drug Design and Discovery

Medicinal chemistry of imidazoquinolinone dopamine receptor agonists

Author: Hsi, R. S. P. ; Lawson, C. F. ; Morris, J. K. ; Moon, M. W. ; Heier, R. F. ; Royer, M. E. ; Manis, M. O. ; Walters, R. R. ; Smith, M. W.

(R)-5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2(1H)-one (I, U-86170), a potent high intrinsic activity dopamine (D2) agonist, has been prepared in eleven steps from quinoline.In several tests, the compound showed dopamine autoreceptor agonist activity at low doses.It showed postsynaptic agonist activity at somewhat higher doses, reversing the effects of reserpine in mice and increasing striatal acetylcholine levels.The compound showed some serotonergic (5HT_1A) activity, but was inactive at other receptors.The related monopropylamine (II, U-91356), also showed good dopaminergic agonist activity, and had improved metabolic stability and oral bioavailability in the rat and monkey when compared to I.Compounds I and II have been prepared in tritiated form, and [³H]I (69 Ci/mmol) has found use as a D2 agonist radioligand in binding assays.The dopaminergic (D2) and serotonergic (5HT_1A) activities of a series of compounds related to I have been evaluated using this ligand, [³H]raclopride, and [³H]8-OH DPAT.

100 Deals associated with U-91356

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Discovery	US	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

Chat with Hiro

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-91356

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation