The chemistry and biology of novel TXA2(TP)-receptor agonists based on the prostanoid skeleton is described and structure-activity-relationships are discussed. One compound,(5Z,13E), (9R,15R)-9-fluoro-15-hydroxy-16-phenoxy-17,18,19,20-tetranor- 5,13-prostadienoic acid (33), was identified which is 10 times more potent than the standard TP-receptor against U 46619.

01 Jan 1991·Agents and Actions

Influence of some prostaglandin-analogues on mouse skin allograft survival compared to dexamethasone. Possible role of thromboxane

Article

Author: K. Becker ; G. Lueddeckens ; W. Förster

The ability of prostaglandin (PG) analogs [iloprost (I), nalador (II), nileprost (III), flunoprost(IV), and U46619 (V)] to prolong the allograft survival of mouse skin without immunosuppressants was determinedI was the most effective compound on proximal and distal allograft transplants.II retarded the rejection in the proximal allograft and IV prolonged the survival of the distal allograft; III and V had no effect.Dexamethasone (DEX) the standard prolonged both grafts, especially the distal allograft.Skin contents of TXB₂ and PGF_2α decreased with applications of I, II and III.DEX had no effect on TXB₂ and PGF_2α levels but increase PGE content.IV and V increased TXB₂ and PGF_2α levels.These results do not support the importance of thromboxane for the monitoring of skin allograft rejection as has been seen for heart allografts.What may be more important is the increase of PGE in the regenerated skin as observed with DEX actions.

01 Jun 1990·Prostaglandins, Leukotrienes and Essential Fatty AcidsQ3 · MEDICINE

Influence of some prostaglandins and prostaglandin analogues on PAF-induced shock in mice

Q3 · MEDICINE

Article

Author: K. Becker ; E. Schillinger ; M.-L. Herfurth ; W. Förster

Prostaglandins and Prostaglandin-analogues were investigated for their ability to protect mice from platelet-activating factor (PAF) induced shock. 75% mortality in female NMRI mice was induced by i.v. injection of 75 micrograms/kg PAF. Nileprost and PGE1, the most potent substances, produced a dose dependent protection against PAF. Iloprost and PGI2 were less effective. PGE2, nalador, flunoprost and U 46619 were neither protective nor deleterious. The strong difference in the effectiveness between the two prostaglandins of the E-series and the poor effect of PGI2 and the PGI2 analogue is remarkable. Flunoprost and U 46619 that increased the TXB2 synthesis or release in two experimental models did not enhance the PAF mortality; TXA2 seems to be only a secondary mediator of the acute PAF-induced death.

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Indication	Highest Phase	Country/Location	Organization	Date
Nasal Obstruction	Phase 1	-	Bayer AG	-

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