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Identification
NameRidogrel
Accession NumberDB01207  (APRD00271)
TypeSmall Molecule
GroupsApproved
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
Synonyms
SynonymLanguageCode
R-68070Not AvailableNot Available
RidogrelNot AvailableNot Available
RidogrelumLatinINN
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number110140-89-1
WeightAverage: 366.3344
Monoisotopic: 366.119127035
Chemical FormulaC18H17F3N2O3
InChI KeyGLLPUTYLZIKEGF-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+
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassNot Available
Direct parentBenzene and Substituted Derivatives
Alternative parentsPyridines and Derivatives; Oxime Ethers; Polyamines; Carboxylic Acids; Enolates; Organofluorides; Imines; Alkyl Fluorides
Substituentsoxime ether; polyamine; enolate; carboxylic acid derivative; carboxylic acid; organohalogen; imine; organofluoride; organonitrogen compound; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the benzene and substituted derivatives. These are aromatic compounds containing at least one benzene ring.
Pharmacology
IndicationUsed as an adjunctive therapy to induce thrombolysis in patients suffering acute myocardial infarction.
PharmacodynamicsRidogrel, 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 actionRidogrel 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.
AbsorptionRapidly absorbed after oral administration (30-60 min)
Volume of distributionNot Available
Protein bindingApproximately 60% bound to plasma proteins
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9925
Blood Brain Barrier + 0.9613
Caco-2 permeable - 0.5694
P-glycoprotein substrate Non-substrate 0.5312
P-glycoprotein inhibitor I Non-inhibitor 0.6419
P-glycoprotein inhibitor II Non-inhibitor 0.8893
Renal organic cation transporter Non-inhibitor 0.5991
CYP450 2C9 substrate Non-substrate 0.8073
CYP450 2D6 substrate Non-substrate 0.7912
CYP450 3A4 substrate Non-substrate 0.5846
CYP450 1A2 substrate Non-inhibitor 0.5
CYP450 2C9 substrate Non-inhibitor 0.6234
CYP450 2D6 substrate Non-inhibitor 0.839
CYP450 2C19 substrate Non-inhibitor 0.5103
CYP450 3A4 substrate Non-inhibitor 0.7368
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7691
Ames test Non AMES toxic 0.6001
Carcinogenicity Non-carcinogens 0.864
Biodegradation Not ready biodegradable 0.9938
Rat acute toxicity 2.5990 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9916
hERG inhibition (predictor II) Non-inhibitor 0.6611
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP4.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00839ALOGPS
logP3.24ALOGPS
logP3.13ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)3.5ChemAxon
pKa (Strongest Basic)4.26ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.78 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity88.89 m3·mol-1ChemAxon
Polarizability34.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound5362391
PubChem Substance46506774
ChemSpider4515025
BindingDB50003795
Therapeutic Targets DatabaseDAP000469
PharmGKBPA164746413
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Thromboxane A2 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Thromboxane A2 receptor P21731 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Thromboxane-A synthase P24557 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13