[3-[4-(4,5-diphenyl-2-oxazolyl)-5-oxazolyl]phenoxy]acetic acid (BMY 45778) is a potent non-prostanoid prostacyclin partial agonist: Effects on platelet aggregation, adenylyl cyclase, cAMP levels, protein kinase, and iloprost binding

Seiler, Steven M.; Brassard, Catherine L.; Federici, Marianne E.; Romine, J.; Meanwell, Nicholas A.

doi:10.1016/s0090-6980(96)00138-4

Cited by 27 publications

(12 citation statements)

References 21 publications

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“…The presence of a diarylhetero(cyclic) moiety in the -chain is crucial . Similar properties were found for octimibate, which lacks a prostanoid ring system (Merritt et al, 1991a,b) and is a member of a series of nonprostanoid prostacyclin mimetics (Meanwell et al, 1994;Seiler et al, 1997). Some of these agents also inhibit (nonprostanoid) Gq-PLC-driven responses (Chow et al, 2001).…”

mentioning

confidence: 52%

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International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Woodward

Jones

Narumiya³

2011

Pharmacol Rev

392

414

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mentioning

confidence: 52%

“…BMY-45778 (Fig. 8) is the most potent agent within this subclass (Jones et al, 1997;Seiler et al, 1997). Caution is necessary in using these agonists to characterize IP receptors because of their high lipophilicity, partial agonism (octimibate; Merritt et al, 1991a) and ability to inhibit G q /PLC-driven effects (Chow et al, 2003).…”

mentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Woodward

Jones

Narumiya³

2011

Pharmacol Rev

392

414

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“…Five candidates were retained as follows: two nonprostanoid IP agonists -59-yl)phenoxy]acetic acid) (Seiler et al, 1997) and MRE-269 ([4-[(5,6-diphenylpyrazinyl)(1-methylethyl)amino]butoxy]-acetic acid) (Morrison et al, 2010)] and three sGC stimulators [A-350619 (3-[2-(4-chlorophenylsulfanyl)phenyl]-N-(4-dimethylaminobutyl)acrylamide hydrochloride) (Miller et al, 2003); SIN-1 (amino-3-morpholinyl-1,2,3-oxadiazolium chloride) (Maurice and Haslam, 1990);and CFM 1571 (3-[3-(dimethylamino)propoxy]-N-(4-methoxyphenyl)-1-(phenylmethyl)-1H-pyrazole-5-carboxamide hydrochloride) (Evgenov et al, 2006) (Fig. 1) MI).…”

Section: Drugsmentioning

confidence: 99%

Anodal Iontophoresis of a Soluble Guanylate Cyclase Stimulator Induces a Sustained Increase in Skin Blood Flow in Rats

Kotzki

Roustit

Arnaud³

et al. 2013

J Pharmacol Exp Ther

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The treatment of systemic sclerosis-related digital ulcers is challenging. Although the only effective drugs are prostacyclin analogs, their use is limited by vasodilation-related adverse reactions. In this study, we assessed the local iontophoresis administration of three soluble guanylate cyclase (A-350619 [3-[2-[(4-chlorophenyl)) and two nonprostanoid prostaglandin I2 (prostacyclin) receptor agonists (1-methylethyl)amino]butoxy]-acetic acid] and BMY 45778 [[3-(4,5-diphenyl[2,49-bioxazol]-59-yl)phenoxy]acetic acid]) to induce vasodilation onto the hindquarters of anesthetized rats. Skin blood flow was quantified using laser Doppler imaging during the whole experience, and safety was assessed by continuous recording of blood pressure and histopathological examination. Anodal iontophoresis of A-350619 (7.54 mM) induced a sustained increase in cutaneous blood flow (P 5 0.008 vs. control). All other drugs exhibited poor or no effect on skin blood flow. Vasodilation with A-350619 iontophoresis was concentration-dependent (7.5, 0.75, and 0.075 mM; P , 0.001, Jonckheere-Terpstra trend test), and repeated administrations do not suggest any risk of tolerance. This study also compared continuous versus intermittent iontophoresis protocols. Continuous anodal iontophoresis of A-350619 at 7.5 mM increases cutaneous blood flow with good local tolerance. Iontophoresis of soluble guanylate cyclase stimulators should be investigated as potential local therapy for digital ulceration in patients with scleroderma.

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“…Non-prostanoid analogs with partial agonist activity ( Fig. 3D) seem to consistently use ester bonds to maintain oxygen positions without including hydroxyls [35,36]. Octimibate-related prostacyclin mimetics act as partial agonists, resulting in an apparent tissue selective response specificity, with the efficacy profile appearing to be influenced by tissue type [37].…”

Section: Prostacyclin Derivativesmentioning

confidence: 99%

“…Stable prostacyclin analogues; C. non-prostanoid prostacyclin mimetics; D. partial hIP agonists, E. dual function hIP agonists / TXA2 antagonists, and F. hIP antagonists. Shown are representative compounds in each group with IC 50 (affinity or function) values and pKi, (affinity) where available[35,[109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124]. (a) IC 50 (function) was determined by inhibition of ADP induced aggregation in human platelet -rich plasma.…”

mentioning

confidence: 99%

Prostacyclin, Atherothrombosis, and Cardiovascular Disease

Arehart¹,

Gleim²,

Kasza³

et al. 2007

CMC

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Prostacyclin (PGI(2)) is a major product of COX-2 catalyzed metabolism of arachidonic acid in the endothelium. Recent studies have demonstrated that PGI(2) protects against atherothrombosis. The prostacyclin receptor knockout mice exhibit increased atherosclerosis, enhanced thrombosis, and enhanced proliferative response to carotid vascular injury with increased intima to media ratios [1-3]. Moreover, the recent withdrawal of rofecoxib (Vioxx) due to increased cardiovascular events further supports the critical role of prostacyclin in inhibiting atherothrombosis in humans. Such studies have paralleled intense chemical biology studies to develop more stable prostacyclin analogues. Indeed a number of these analogues are currently being successfully used for the treatment of pulmonary hypertension. In this review we will summarize the current literature on some principles of prostacyclin analogue development, our current understanding of the receptor, and recent developments which implicate prostacyclin in atherothrombotic protection. More than 68 million Americans suffer from cardiovascular disease, which causes more deaths, disability and economic loss than any other group of diseases. Further clinical investigations of orally stable prostacyclin analogues for treatment of cardiovascular diseases other than pulmonary hypertension may now be warranted.

show abstract

[3-[4-(4,5-diphenyl-2-oxazolyl)-5-oxazolyl]phenoxy]acetic acid (BMY 45778) is a potent non-prostanoid prostacyclin partial agonist: Effects on platelet aggregation, adenylyl cyclase, cAMP levels, protein kinase, and iloprost binding

Cited by 27 publications

References 21 publications

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Anodal Iontophoresis of a Soluble Guanylate Cyclase Stimulator Induces a Sustained Increase in Skin Blood Flow in Rats

Prostacyclin, Atherothrombosis, and Cardiovascular Disease

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