Synthesis and pharmacological evaluation of combined Thromboxane receptor antagonists/thromboxane synthase inhibitors: Pyridine-containing amino-prostanoids

Campbell, Ian B.; Collington, E. W.; Finch, Harry; Hayes, Roger N.; Lumley, P. J.; Mills, K.; Robertson, Graeme M.; Wharton, Kayla; Watts, Ian S.

doi:10.1016/s0960-894x(01)81050-7

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…ZD‐1542 (Brownlie et al. , 1993) is a pyridin‐3‐yl derivative related to ICI‐192605, while GR‐83783 (Campbell et al. , 1991a), a relative of GR‐32191, has a 4‐(pyridin‐3‐yl)‐phenyl moiety (Figure 8).…”

Section: Tp Receptor Antagonistsmentioning

confidence: 99%

Prostanoid receptor antagonists: development strategies and therapeutic applications

Jones

Giembycz

Woodward³

2009

British J Pharmacology

144

162

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Identification of the primary products of cyclo-oxygenase (COX)/prostaglandin synthase(s), which occurred between 1958 and 1976, was followed by a classification system for prostanoid receptors (DP, EP1, EP2 . . .) based mainly on the pharmacological actions of natural and synthetic agonists and a few antagonists. The design of potent selective antagonists was rapid for certain prostanoid receptors (EP1, TP), slow for others (FP, IP) and has yet to be achieved in certain cases (EP2). While some antagonists are structurally related to the natural agonist, most recent compounds are 'non-prostanoid' (often acyl-sulphonamides) and have emerged from high-throughput screening of compound libraries, made possible by the development of (functional) assays involving single recombinant prostanoid receptors. Selective antagonists have been crucial to defining the roles of PGD2 (acting on DP1 and DP2 receptors) and PGE2 (on EP1 and EP4 receptors) in various inflammatory conditions; there are clear opportunities for therapeutic intervention. The vast endeavour on TP (thromboxane) antagonists is considered in relation to their limited pharmaceutical success in the cardiovascular area. Correspondingly, the clinical utility of IP (prostacyclin) antagonists is assessed in relation to the cloud hanging over the long-term safety of selective COX-2 inhibitors. Aspirin apart, COX inhibitors broadly suppress all prostanoid pathways, while high selectivity has been a major goal in receptor antagonist development; more targeted therapy may require an intermediate position with defined antagonist selectivity profiles. This review is intended to provide overviews of each antagonist class (including prostamide antagonists), covering major development strategies and current and potential clinical usage.

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Section: Tp Receptor Antagonistsmentioning

confidence: 99%

Prostanoid receptor antagonists: development strategies and therapeutic applications

Jones

Giembycz

Woodward³

2009

British J Pharmacology

144

162

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“…11) to combine with the heme site of the synthase (see Hsu et al, 1999). Existing TP antagonists have also been modified to include similar reactive moieties: ZD-1542 (Brownlie et al, 1993), a relative of ICI-192605, contains a pyridin-3-yl group and GR-83783 (Campbell et al, 1991a), a relative of GR-32191, has a 4-(pyridin-3-yl)-phenyl moiety. In addition, sulotroban/daltroban moieties have been combined with ridogrel/isbogrel moieties (Campbell et al, 1991b;CGS-22652 (Bhagwat et al, 1993;Soyka et al, 1994) and the whole or part of the ICI-192605 nucleus has been tethered to either a dazoxiben or an isbogrel nucleus (Ackerley et al, 1995).…”

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

395

414

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“…As in the case of the thiaprostanoid, CGS 4642 (Fig. 8), the structural complexity of GR 32191 could be simplified by the introduction of a heteroatom such as sulfur or oxygen in place of the hydroxymethine moiety in GR 32191 without compromising the intrinsic activity of the parent compound [63].…”

Section: -Synthesis and Biological Activity Of Heterocyclic Prostmentioning

confidence: 99%

Synthesis and Biological Activity of Prostaglandin Analogs Containing Heteroatoms in the Cyclopentane Ring

Biaggio¹,

Rufino²,

Zaim³

et al. 2005

COC

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Prostaglandins (PG's) are a very important class of naturally occurring physiologically active substances, which have been the subject of continuous attention by biologists, pharmacists and chemists since their discovery in the 1930s. Pharmacological studies have shown that prostaglandins exhibit an extremely broad spectrum of activity such as on the smooth muscles of various organs, their mediating role in the central and peripheral nervous systems, in inflammatory processes, and their hormone-like and antihormonal activities. Due to the diversified biological activity and rapid metabolism of the natural prostaglandins, a lot of effort has been done to synthesize prostaglandin analogs. Particularly interesting are the prostaglandin analogs containing heteroatoms in the cyclopentane ring which have received a great deal of attention in relation to their potential biological properties and diversified biological activity.This article is dedicated to Prof. Sune K. Bergstrom (in memoriam) for his milestone contributions to prostaglandin research.

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Synthesis and pharmacological evaluation of combined Thromboxane receptor antagonists/thromboxane synthase inhibitors: Pyridine-containing amino-prostanoids

Cited by 6 publications

References 12 publications

Prostanoid receptor antagonists: development strategies and therapeutic applications

Prostanoid receptor antagonists: development strategies and therapeutic applications

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

Synthesis and Biological Activity of Prostaglandin Analogs Containing Heteroatoms in the Cyclopentane Ring

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