Delving into the Latest Updates on Parogrelil Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Parogrelil

+ [1]

Target

PDE3 x calcium channel

Mechanism

PDE3 inhibitors(Phosphodiesterase 3 inhibitors), calcium channel inhibitors(Calcium Channel inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Intermittent Claudication

Inactive Indication

AsthmaPeripheral Vascular Diseases

Originator Organization

Nissan Chemical Corp.

Active Organization

Taisho Pharmaceutical Co., Ltd.

Inactive Organization

Nissan Chemical Corp.

Taisho Pharmaceutical Holdings Co., Ltd.HP Indigo Ltd.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC19H19BrCl2N4O2

InChIKeyQWGUGDYWUADMGB-UHFFFAOYSA-N

CAS Registry139145-84-9

View All Structures (2)

We evaluated the effects of NT-702 (parogrelil hydrochloride, NM-702, 4-bromo-6-[3-(4-chlorophenyl) propoxy]-5-[(pyridine-3-ylmethyl) amino] pyridazin-3(2H)-one hydrochloride), a selective phosphodiesterase 3 inhibitor, on the asthmatic response in guinea pigs. NT-702 at a concentration of 1 x 10(-7)M elevated the cyclic adenosine monophosphate content in prostaglandin E(2)-treated guinea pig tracheal smooth muscle cells. Leukotriene (LT) D(4)- and histamine-induced contraction of isolated guinea pig tracheal strips was inhibited by NT-702, with EC(50) values of 3.2 x 10(-7) and 2.5 x 10(-7)M, respectively. In an in vivo study, NT-702 suppressed LTD(4)-induced bronchoconstriction and the ovalbumin-induced immediate asthmatic response in guinea pigs through its bronchodilating effect. Furthermore, NT-702 also suppressed the ovalbumin-induced late asthmatic response, airway hyperresponsiveness, and the accumulation of inflammatory cells in the bronchoalveolar lavage fluid. These results suggest that NT-702 has an anti-inflammatory effect as well as a bronchodilating effect and might be useful as a novel potent therapeutic agent for the treatment of bronchial asthma, a new type of agent with both a bronchodilating and an anti-inflammatory effect.

01 Jan 2008·The Journal of Physiological SciencesQ4 · MEDICINE

NT-702, a Selective Phosphodiesterase 3 Inhibitor, Dilates Rabbit Spinal Arterioles via Endothelium-Dependent and Endothelium-Independent Mechanisms

Q4 · MEDICINE

Article

Author: Risuke Mizuno ; Toshio Ohhashi ; Sachiko Watanabe

We investigated the effects of NT-702, a selective phosphodiesterase (PDE) 3 inhibitor, on arterioles isolated from rabbit lumbar spinal cords. NT-702 caused a dose-dependent dilation of the isolated spinal arterioles. The disruption of endothelium produced a significant reduction of higher concentrations (10(-7) and 10(-6) M), but not lower concentrations (less than 10(-8) M), of NT-702-induced vasodilation. The NT-702-induced vasodilation of the arterioles with endothelium was not affected by pretreatment with an inhibitor of nitric oxide, cyclooxygenase, or cytochrome P-450 monooxygenase. In contrast, catalase reduced significantly the higher concentrations of NT-702-induced vasodilation only. Tetraethylammonium (TEA) completely reduced the lower concentrations of NT-702-induced vasodilation, but decreased only partially the higher concentrations of NT-702-induced vasodilation of the arterioles with endothelium. Hydrogen peroxide dilated significantly the isolated arterioles with endothelium, the response of which was reduced significantly by TEA. KT5720 (a selective protein kinase inhibitor) significantly decreased both the lower and higher concentrations of NT-702-induced vasodilation of the arterioles with endothelium. The findings suggest that NT-702 dose-dependently dilated the isolated spinal arterioles of rabbits via endothelium-dependent and endothelium-independent mechanisms. Protein kinase A (PKA)- and TEA-sensitive K(+) channels may be involved in the NT-702-induced vasodilation. Moreover, hydrogen peroxide may contribute in part to the endothelium-dependent higher concentrations of NT-702-induced vasodilation.

01 Sep 2007·Life SciencesQ3 · MEDICINE

NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase inhibitor, improves reduced walking distance and lowered hindlimb plantar surface temperature in a rat experimental intermittent claudication model

Q3 · MEDICINE

Article

Author: Nobutomo Tsuruzoe ; Kenzo Takahashi ; Masafumi Kawanishi ; Norihisa Ishiwata ; Yusuke Ito ; Norimasa Shudo ; Shuya Takahashi ; Yumiko Asakura ; Hiroshi Nishiyama ; Akiko Mitani ; Kazuo Noguchi ; Shiro Nakaike ; Miyuki Hori ; Kanako Takahashi

NT-702 (parogrelil hydrochloride, NM-702), 4-bromo-6-[3-(4-chlorophenyl)propoxy]-5-[(pyridin-3-ylmethyl)amino]pyridazin-3(2H)-one hydrochloride, a novel phosphodiesterase (PDE) inhibitor synthesized as a potent vasodilatory and antiplatelet agent, is being developed for the treatment of intermittent claudication (IC) in patients with peripheral arterial disease. We assessed the efficacy of NT-702 in an experimental IC model as compared with cilostazol and additionally investigated the pharmacological property in vitro and ex vivo. NT-702 selectively inhibited PDE3 (IC(50)=0.179 and 0.260 nM for PDE3A and 3B) more potently than cilostazol (IC(50)=231 and 237 nM for PDE3A and 3B) among recombinant human PDE1 to PDE6. NT-702 inhibited in vitro human platelet aggregation induced by various agonists (IC(50)=11 to 67 nM) and phenylephrine-induced rat aortic contraction (IC(50)=24 nM). Corresponding results for cilostazol were 4.1 to 17 microM and 1.0 microM, respectively. NT-702 (3 mg/kg or more) significantly inhibited ex vivo rat platelet aggregation after a single oral dose. For cilostazol, 300 mg/kg was effective. In a rat femoral artery ligation model, NT-702 at 5 and 10 mg/kg repeated oral doses twice a day (BID) for 13 days significantly improved the reduced walking distance while the lowered plantar surface temperature was improved at 2.5 mg/kg and more. Cilostazol also improved the walking distance and surface temperature at 300 mg/kg BID but significant difference was only observed for surface temperature on day 8. These results suggest that NT-702 can be expected to have therapeutic advantage for IC.

100 Deals associated with Parogrelil Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05505

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Peripheral Vascular Diseases	Phase 2	US	Nissan Chemical Corp.	01 Apr 2003
Asthma	Discovery	JP	Nissan Chemical Corp.	-
Intermittent Claudication	Discovery	-	Taisho Pharmaceutical Holdings Co., Ltd.	-
Intermittent Claudication	Discovery	-	HP Indigo Ltd.	-