2,4-Disubstituted oxazoles and thiazoles as latent pharmacophores for diacylhydrazine of SC-51089, a potent PGE2 antagonist

Hallinan, E. Ann; Hagen, Timothy J.; Tsymbalov, Sofya; Stapelfeld, Awilda; Savage, Michael A.

doi:10.1016/s0968-0896(00)00229-7

Cited by 47 publications

(25 citation statements)

References 13 publications

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“…In order to determine whether EP1 receptors are also involved, the EP1 receptor antagonist SC-51089 [32][33][34] was employed. Initially, the effect of increasing concentrations of SC-51089 on the stimulatory effect of 0.028 μM PGE 1 was examined.…”

Section: Pge 1 Stimulation Of the β1 Promoter: Signaling Through Ep1 mentioning

confidence: 99%

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Matlhagela

Taub

2006

Prostaglandins & Other Lipid Mediators

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Prostaglandins are key regulators of ion transport in the kidney. In MDCK cells, which model distal tubule cells, the transcription of the Na,K-ATPase β1 subunit is regulated by PGE 1 and PGE 2 . To identify the EP receptors that mediate transcriptional regulation, transient transfection studies are conducted using the human β1 promoter/luciferase construct, pHβ1-1141 Luc. The involvement of EP1 and EP2 receptors is indicated by studies with the EP1 selective agonist 17-phenyl trinor PGE 2 , and the EP2 selective agonist butaprost (which stimulate), as well as by studies with the antagonists SC-51089 (EP1 specific) and AH 6809 (EP1 and EP2 specific). Consistent with the involvement of Gs coupled EP2 receptors, is that the PGE 1 stimulation is inhibited by the PKAI expression vector (encoding the protein kinase A (PKA) inhibitory protein), as well as by the myristolated PKA inhibitory peptide PKI. In addition to this evidence (for the involvement of EP2 receptors), evidence for the involvement of EP1 receptors in the PGE 1 mediated stimulation of Na,KATPase β subunit gene transcription includes the stimulatory effect of 17-phenyl trinor PGE 2 , as well as the inhibitory effects of SC-51089. Also consistent with the involvement of Gq coupled EP1 receptors, the PGE 1 stimulation is inhibited by the PKCI vector (encoding the PKC inhibitory domain), the PKC inhibitor Go 6976, thapsigargin, as well as the calmodulin antagonists W7 and W13.

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Section: Pge 1 Stimulation Of the β1 Promoter: Signaling Through Ep1 mentioning

confidence: 99%

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Matlhagela

Taub

2006

Prostaglandins & Other Lipid Mediators

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“…Although specific data are not presented, the indicated affinity of the preferred compounds indicates them to compare favourably with many of the known EP 1 antagonists such as SC-51089 [5]. However, very limited data has been published on the AstraZeneca compounds, with just one small scale clinical study with ZD-6416 having been described [6].…”

Section: Expert Opinionmentioning

confidence: 99%

Novel EP1 receptor antagonists

2004

Expert Opinion on Therapeutic Patents

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“…Three isomeric forms of dibenzoxazepine systems are possible -dibenz[b,f] [1,4]oxazepine (DBO) 1, dibenz[b,e] [1,4] oxazepine 2, and dibenz[c,f] [1,2]oxazepine 3 ( Figure 1). …”

Section: Introductionmentioning

confidence: 99%

“…Compounds containing chemotype 1 include antidepressants [1], analgesics [2], calcium channel antagonists [3], a histamine H 4 receptor agonist [4], a non-nucleoside HIV-1 reverse transcriptase inhibitor [5], and a lachrymatory agent [6]. This review provides synthetic chemists with an update on the progress in the synthesis of DBO derivatives.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in dibenzo[b,f][1,4]oxazepine synthesis

Zaware

Ohlmeyer

2014

Heterocyclic Communications

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Dibenzo[b,f] [1,4]oxazepine (DBO) derivatives possess an array of pharmacological activities, and are of growing pharmaceutical interest. Twelve recent synthetic protocols to construct DBO and DBO derivatives have been described in this review. The reported methods include cyclocondensation with two precursors exemplified by substituted 2-aminophenols and substituted 2-halobenzaldehydes, substituted 2-nitro-1-bromobenzene and substituted 2-triazolylphenols, substituted 2-nitro-1-bromobenzene and substituted 2-hydrazonamidophenol, substituted 2-nitro-1-bromobenzene and substituted 2-(aminomethyl)phenol, and 2-aminobenzonitrile and 1,4-dichloro-2-nitrobenzene. Other methods include copper catalysis, 1,3-dipolar cycloaddition, domino elimination-rearrangement-addition sequence, and an Ugi four-component reaction followed by an intramolecular O-arylation. These methods will serve as a guide to chemists in developing DBO derivatives of pharmacological interest.

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2,4-Disubstituted oxazoles and thiazoles as latent pharmacophores for diacylhydrazine of SC-51089, a potent PGE2 antagonist

Cited by 47 publications

References 13 publications

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

Novel EP1 receptor antagonists

Recent advances in dibenzo[b,f][1,4]oxazepine synthesis

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