Identification

Name
Ridogrel
Accession Number
DB01207  (APRD00271)
Type
Small Molecule
Groups
Experimental
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
  • Ridogrelum
External IDs
R 68070 / R-68070
Categories
UNII
QTS5QOO42O
CAS number
110140-89-1
Weight
Average: 366.3344
Monoisotopic: 366.119127035
Chemical Formula
C18H17F3N2O3
InChI Key
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+
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

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.

TargetActionsOrganism
AThromboxane A2 receptor
antagonist
Human
AThromboxane-A synthase
inhibitor
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Ridogrel is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Ridogrel is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Ridogrel is combined with 4-hydroxycoumarin.
AbciximabRidogrel may increase the anticoagulant activities of Abciximab.
AcenocoumarolThe risk or severity of bleeding can be increased when Ridogrel is combined with Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Ridogrel is combined with Acetylsalicylic acid.
AlaproclateThe risk or severity of hemorrhage can be increased when Alaproclate is combined with Ridogrel.
AldesleukinThe risk or severity of bleeding can be increased when Ridogrel is combined with Aldesleukin.
AlemtuzumabThe risk or severity of bleeding can be increased when Ridogrel is combined with Alemtuzumab.
AloxiprinThe risk or severity of adverse effects can be increased when Ridogrel is combined with Aloxiprin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015338
PubChem Compound
5362391
PubChem Substance
46506774
ChemSpider
4515025
BindingDB
50003795
ChEBI
135542
ChEMBL
CHEMBL280728
Therapeutic Targets Database
DAP000469
PharmGKB
PA164746413

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00839 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9613
Caco-2 permeable-0.5694
P-glycoprotein substrateNon-substrate0.5312
P-glycoprotein inhibitor INon-inhibitor0.6419
P-glycoprotein inhibitor IINon-inhibitor0.8893
Renal organic cation transporterNon-inhibitor0.5991
CYP450 2C9 substrateNon-substrate0.8073
CYP450 2D6 substrateNon-substrate0.7912
CYP450 3A4 substrateNon-substrate0.5846
CYP450 1A2 substrateNon-inhibitor0.5
CYP450 2C9 inhibitorNon-inhibitor0.6234
CYP450 2D6 inhibitorNon-inhibitor0.839
CYP450 2C19 inhibitorNon-inhibitor0.5103
CYP450 3A4 inhibitorNon-inhibitor0.7368
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7691
Ames testNon AMES toxic0.6001
CarcinogenicityNon-carcinogens0.864
BiodegradationNot ready biodegradable0.9938
Rat acute toxicity2.5990 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9916
hERG inhibition (predictor II)Non-inhibitor0.6611
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Trifluoromethylbenzenes
Direct Parent
Trifluoromethylbenzenes
Alternative Parents
Pyridines and derivatives / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives
show 2 more
Substituents
Trifluoromethylbenzene / Pyridine / Heteroaromatic compound / Carboxylic acid derivative / Carboxylic acid / Monocarboxylic acid or derivatives / Organoheterocyclic compound / Azacycle / Alkyl fluoride / Hydrocarbon derivative
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Details
1. Thromboxane A2 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Thromboxane a2 receptor activity
Specific Function
Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messen...
Gene Name
TBXA2R
Uniprot ID
P21731
Uniprot Name
Thromboxane A2 receptor
Molecular Weight
37430.69 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:8831771]
  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:8289199]
  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:10522750]
  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:9272380]
  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:8697470]
Details
2. Thromboxane-A synthase
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Thromboxane-a synthase activity
Specific Function
Not Available
Gene Name
TBXAS1
Uniprot ID
P24557
Uniprot Name
Thromboxane-A synthase
Molecular Weight
60517.69 Da
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:11270983]
  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:11856082]
  3. Authors unspecified: 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:8313547]
  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:8376914]
  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:10848666]
  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:10592235]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:58