Delving into the Latest Updates on PD-148903 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

PD-148903 derivatives(Parke-Davis), (S)-PD-148903, PD-148903

Target

D1 receptor x D2 receptor

Action

agonists

Mechanism

D1 receptor agonists(Dopamine D1 receptor agonists), D2 receptor agonists(Dopamine D2 receptor agonists)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Parkinson Disease

Originator Organization

Parke-Davis & Co. Ltd.

Active Organization-

Inactive Organization

Parke-Davis & Co. Ltd.

License Organization-

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC16H27NO

InChIKeyJTYVLKBMXTUORS-UHFFFAOYSA-N

CAS Registry256474-06-3

A series of racemic and enantiomerically pure oxime derivatives of the potential anti-Parkinson prodrug 6-(N,N-di-n-propylamino)-3,4,5,6,7,8-hexahydro-2H-naphthalen-1-one (1) were synthesized and pharmacologically evaluated. The oximes induced rotational behavior in the Ungerstedt rat rotation model for Parkinson's disease after oral administration. Especially the unsubstituted oxime ((-)-3) and the acetyl-oxime ((-)-10) induced a pronounced and long lasting effect. In this model, large individual differences were observed in responsiveness to treatment between rats. Though less potent than the parent prodrug, the oxime derivatives of (+/-)-1 and (-)-1 can be orally active, acting as cascade prodrugs.

01 Jun 2002·Journal of medicinal chemistryQ1 · MEDICINE

A New Type of Prodrug of Catecholamines: An Opportunity to Improve the Treatment of Parkinson's Disease

Q1 · MEDICINE

Article

Author: Johnson, Stephen J ; Dijkstra, Durk ; Meltzer, Leonard T ; Venhuis, Bastiaan J ; Wustrow, David ; Sundell, Staffan ; Rodenhuis, Nienke ; Wise, Lawrence D ; Wikström, Håkan V ; Pugsley, Thomas A

After decades of research around dopamine agonists, we have found a promising compound in S-PD148903 that represents a new type of prodrug, which in the rat is bioactivated to the catecholamine S-5,6-diOH-DPAT, known to display mixed dopamine D(1)/D(2) receptor agonist properties just like apomorphine. This prodrug has an enone structure which by an oxidative bioactivation mechanism is converted to the corresponding catechol and is delivered enantioselectively into the CNS. This novel concept has the potential to revolutionize the treatment of Parkinson's disease by competing with L-DOPA, the current treatment of choice.

100 Deals associated with PD-148903

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