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Identification
Name Ridogrel
Accession Number DB01207 (APRD00271)
Type small molecule
Groups approved
Description

Ridogrel is a dual action drug useful for the prevention of systemic thrombo-embolism and as an adjunctive agent to thrombolytic therapy in acute myocardial infarction. However, there currently are no clinical indications for preferential use of ridogrel over aspirin.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Ridogrelum [INN-Latin]
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Thrombolytic Agents
  • Platelet Aggregation Inhibitors
  • Enzyme Inhibitors
  • Gastrointestinal Agents
CAS number 110140-89-1
Weight Average: 366.3344
Monoisotopic: 366.119127035
Chemical Formula C18H17F3N2O3
InChI Key InChIKey=GLLPUTYLZIKEGF-HAVVHWLPSA-N
InChI
InChI=1S/C18H17F3N2O3/c19-18(20,21)15-7-3-5-13(11-15)17(14-6-4-9-22-12-14)23-26-10-2-1-8-16(24)25/h3-7,9,11-12H,1-2,8,10H2,(H,24,25)/b23-17+
Plain Text
IUPAC Name
5-{[(E)-{pyridin-3-yl[3-(trifluoromethyl)phenyl]methylidene}amino]oxy}pentanoic acid
SMILES
OC(=O)CCCCO\N=C(\C1=CN=CC=C1)C1=CC(=CC=C1)C(F)(F)F
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyridines and Derivatives
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
Substructures
  • Hydroxy Compounds
  • Acetates
  • Oximes and Derivatives
  • Pyridines and Derivatives
  • Halogen Derivatives
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
Pharmacology
Indication Used as an adjunctive therapy to induce thrombolysis in patients suffering acute myocardial infarction.
Pharmacodynamics Ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, is used with streptokinase as an adjunctive therapy to reduce the formation and size of blood clots. Blood clots can cause ischemic cardiac events (heart attacks). Ridogrel has the dual property of inhibiting the synthesis of thromboxane and blocking the receptors of thromboxane/prostaglandin/endoperoxides. It has been shown to accelerate the speed of recanalization and to delay or prevent reocclusion during systemic thrombolysis with tissue plasminogen activator (streptokinase). Ridogrel is a more potent antiplatelet agent than aspirin and might offer an advantage over aspirin as an adjunct to thrombolysis in patients suffering from acute myocardial infarction. While aspirin inhibits cyclooxygenase, the enzyme responsible for producing thromboxane, ridogrel inhibits thromboxane synthesis directly. A recent comparison between aspirin and ridogrel in as adjunct to thrombolysis in patients with acute myocardial infarction demonstrated that ridogrel is not superior to aspirin in enhancing the fibrinolytic efficacy of streptokinase but might be more effective in preventing new ischemic events. Clinical experience with this drug is still relatively limited.
Mechanism of action Ridogrel inhibits thromboxane A2 synthase and also blocks the thromboxane A2/prostaglandin endoperoxide receptors. Thromboxane synthetase produces thromboxane in platelets. Thromboxane is a vasoconstrictor and facilitates the clumping of platelets. Therefore by inhibiting the production and promotion of thromboxane, thrombolysis is enhanced.
Absorption Rapidly absorbed after oral administration (30-60 min)
Volume of distribution Not Available
Protein binding Approximately 60% bound to plasma proteins
Metabolism
Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP 4.3 Not Available
Predicted Properties
Property Value Source
water solubility 8.39e-03 g/l ALOGPS
logP 3.24 ALOGPS
logP 3.13 ChemAxon
logS -4.6 ALOGPS
pKa (strongest acidic) 3.5 ChemAxon
pKa (strongest basic) 4.26 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 71.78 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 88.89 ChemAxon
polarizability 34.94 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 5362391 Link_out
PubChem Substance 46506774 Link_out
ChemSpider 4515025 Link_out
BindingDB 50003795 Link_out
Therapeutic Targets Database DAP000469 Link_out
PharmGKB PA164746413 Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Thromboxane A2 receptor

Pharmacological action: yes
Actions: antagonist

Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction

Organism class: human
UniProt ID: P21731 Link_out
Gene: TBXA2R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Heinisch G, Holzer W, Kunz F, Langer T, Lukavsky P, Pechlaner C, Weissenberger H: On the bioisosteric potential of diazines: diazine analogues of the combined thromboxane A2 receptor antagonist and synthetase inhibitor Ridogrel. J Med Chem. 1996 Sep 27;39(20):4058-64. Pubmed
  3. Soyka R, Heckel A, Nickl J, Eisert W, Muller TH, Weisenberger H: 6,6-Disubstituted Hex-5-enoic acid derivatives as combined thromboxane A2 receptor antagonists and synthetase inhibitors. J Med Chem. 1994 Jan 7;37(1):26-39. Pubmed
  4. Hempelmann RG, Pradel RH, Mehdorn HM, Ziegler A: Threshold concentrations of endothelin-1: the effects on contractions induced by 5-hydroxytryptamine in isolated rat cerebral and mesenteric arteries. Pharmacol Toxicol. 1999 Sep;85(3):115-22. Pubmed
  5. Carvalho MH, Fortes ZB, Nigro D, Oliveira MA, Scivoletto R: The role of thromboxane A2 in the altered microvascular reactivity in two-kidney, one-clip hypertension. Endothelium. 1997;5(3):167-78. Pubmed
  6. Ragni M, Golino P, Cirillo P, Pascucci I, Scognamiglio A, Ravera A, Esposito N, Battaglia C, Guarino A, Chiariello M: [Inactivated factor VII exercises a powerful antithrombotic activity in an experimental model of recurrent arterial thrombosis] Cardiologia. 1996 Jan;41(1):51-8. Pubmed

2. Thromboxane-A synthase

Pharmacological action: yes
Actions: inhibitor

(5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15- hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-9-alpha,11-alpha- epoxy-15-hydroxythromboxa-5,13-dienoate

Organism class: human
UniProt ID: P24557 Link_out
Gene: TBXAS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Park SJ, Lee JJ, Vanhoutte PM: Endothelin-1 releases endothelium-derived endoperoxides and thromboxane A2 in porcine coronary arteries with regenerated endothelium. Zhongguo Yao Li Xue Bao. 1999 Oct;20(10):872-8. Pubmed
  2. Tytgat GN, Van Nueten L, Van De Velde I, Joslyn A, Hanauer SB: Efficacy and safety of oral ridogrel in the treatment of ulcerative colitis: two multicentre, randomized, double-blind studies. Aliment Pharmacol Ther. 2002 Jan;16(1):87-99. Pubmed
  3. Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in patients with acute myocardial infarction. The Ridogrel Versus Aspirin Patency Trial (RAPT). Circulation. 1994 Feb;89(2):588-95. Pubmed
  4. De Cree J, Geukens H, Gutwirth P, De Clerck F, Vercammen E, Verhaegen H: The effect of a combined administration of ridogrel and ketanserin in patients with intermittent claudication. Int Angiol. 1993 Mar;12(1):59-68. Pubmed
  5. Carty E, Macey M, McCartney SA, Rampton DS: Ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist: anti-inflammatory profile in inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Jun;14(6):807-17. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:20