Delving into the Latest Updates on RWJ-38063 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

α1A-AR

Mechanism

α1A-AR antagonists(Alpha-1a adrenergic receptor antagonists)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Prostatic Hyperplasia

Originator Organization

Johnson & Johnson Pharmaceutical Research & Development LLC

Active Organization-

Inactive Organization

Johnson & Johnson Pharmaceutical Research & Development LLC

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H34N4O3

InChIKeyIIRJWNCOXHFIBK-UHFFFAOYSA-N

CAS Registry216252-56-1

The development of alpha(1a)-adrenergic receptor (AR) subtype-selective antagonists is likely to result in uroselective agents that effectively treat benign prostatic hyperplasia (BPH) symptoms without causing undesirable side effects that may be due to vascular alpha(1)-AR blockade. The properties of four aryl piperazine compounds (RWJ-38063, RWJ-68141, RWJ-68157, and RWJ-69736) are described in this report and compared with the properties of tamsulosin, an alpha(1)-AR antagonist that is used in the treatment of BPH. Radioligand binding studies show that all four RWJ compounds have significantly higher affinity for the alpha(1a)-AR subtype than for the alpha(1b) or alpha(1d) subtype and display a higher level of receptor subtype selectivity than tamsulosin. The RWJ compounds were more potent in inhibiting (+/-)-norepinephrine-induced contractions of isolated rat prostate tissue than those of isolated rat aorta tissue, whereas tamsulosin had the reversed tissue selectivity. RWJ-38063 and RWJ-69736 had the highest potency in the isolated prostate tissue assays of the four RWJ compounds, with pK(B) values of 8.24 and 9.26, respectively, and were 319- and 100-fold more potent in their effects on isolated prostate tissue than aorta tissue. The in vivo uroselectivities of RWJ-38063, RWJ-69736, and tamsulosin were examined in anesthetized dogs. Both RWJ compounds suppressed the intraurethral pressure response to phenylephrine to a greater extent than the mean arterial pressure response; however, RWJ-69736 also caused a marked transient rise in heart rate. Although less potent, RWJ-38063 and RWJ-69736 were notably more uroselective than tamsulosin in this canine model.

100 Deals associated with RWJ-38063

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