TP receptor as a therapeutic target in atherosclerosis and related cardiovascular diseases.

Abstract

It had already showed that several thromboxane A(2) receptor (TP receptor) antagonists might be utilized in the treatment of cardiovascular diseases. In addition, recent reports suggested that TP receptor antagonism may be able to restrict vascular inflammation in atherosclerotic vessels. In particular, S18886 has been developed as a non-prostanoid TP receptor antagonist derived from sulotroban that is characterized by a tetrahydronaphthalene ring as a spacer between the 4-cholophenylsulfonamide group and carboxylic acid. Several reports using experimental animal models of atherosclerosis indicated that S18886 caused a regression of advanced atherosclerosis. More recently, several studies and patents showed that new thromboxane modulators combined with another pharmacological activities have been developed. Ohtake et al. discovered TRA-418 (a benzene-condensed heterocyclic derivative) having a TP receptor antagonistic activity and a prostaglandin I(2) receptor agonistic activity. Cesagrande found that 4-methyl-N- (4-trans-nitrooxycyclohexyl)-N-(3-pyridinylmethyl)-1,3- benzenedicarboxamide is endowed with anti-thromboxane and NO-donor actions. Oketani et al. discovered that E3040, a novel benzothiazole derivative, inhibited TXA(2) synthase and 5-LO activities. EK112, a combined angiotensin II and TP receptor antagonist, was developed. These new compounds may be able to restrict further infiltration of inflammatory cells in atherosclerotic vessels, thus stabilizing vulnerable plaques in the related cardiovascular diseases.

• Authors: Toshiaki Ishizuka, Hideaki Higashino
• Journal: Recent patents on cardiovascular drug discovery (Recent Pat Cardiovasc Drug Discov) Vol. 1 Issue 3 Pg. 241-7 (Nov 2006) United Arab Emirates
• PMID: 18221089 (Publication Type: Journal Article)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Fatty Acids, Unsaturated
• Hydrazines
• Lipoxygenase Inhibitors
• Naphthalenes
• Propionates
• Receptors, Thromboxane A2, Prostaglandin H2
• SQ 29548
• terutroban

Topics

• Animals
• Atherosclerosis (drug therapy)
• Bridged Bicyclo Compounds, Heterocyclic
• Cardiovascular Diseases (drug therapy)
• Fatty Acids, Unsaturated
• Humans
• Hydrazines (therapeutic use)
• Lipoxygenase Inhibitors
• Naphthalenes (therapeutic use)
• Oxidative Stress
• Propionates (therapeutic use)
• Receptors, Thromboxane A2, Prostaglandin H2 (antagonists & inhibitors, physiology)
• Signal Transduction