Delving into the Latest Updates on FR-166124 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

A1R

Mechanism

A1R antagonists(Adenosine A1 receptor antagonists)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Acute Kidney Injury

Originator Organization

Fujisawa Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Fujisawa Pharmaceutical Co., Ltd.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

A novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazol o[1,5-a]pyridines was synthesized and evaluated for in vitro adenosine A1 and A2A receptor binding activities. Most of the cyclohexenyl derivatives (7a-e, 8a-s) were found to be potent adenosine A1 receptor antagonists. In a series of analogues of FR166124 (3a), alcohol 7c, nitrile 7e and amide derivatives (7d, 8c, 8r) were found to be more potent A1 antagonists with higher A2A/A1 selectivity than FR166124. Amongst them, 8r showed considerable water solubility (33.3 mg/mL), but lower than that of the sodium salt of FR166124 (> 200 mg/mL). Additionally, FR166124 had strong diuretic activity by both p.o. and iv administration in rats (minimum effective dose=0.1 and 0.032 mg/kg, respectively).

01 Jul 1999·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-α]pyridine adenosine A1 receptor antagonist

Q4 · MEDICINE

Article

Author: Tenda, Yoshiyuki ; Durkin, Kieran ; Kinoshita, Takayoshi ; Itani, Hiromichi ; Sakane, Kazuo ; Nishimura, Shintaro ; Akahane, Atsushi ; Kuroda, Satoru

Novel 3-(2-cycloalkyl and cycloalkenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazo lo [1,5-a]-pyridines were synthesized and evaluated for their adenosine A1 receptor binding activities. In this series, FR166124 (3) was found to be the most potent and selective adenosine A1 receptor antagonist, and the double bond of the cyclohexenyl acetic acid group was essential for selectivity of A1 receptor binding. Furthermore, the solubility in water of the sodium salt of FR 166124 was high.

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