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

Similar Structures

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.

Target	Actions	Organism
AThromboxane A2 receptor	antagonist	Humans
AThromboxane-A synthase	inhibitor	Humans

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

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
(R)-warfarin	The risk or severity of bleeding can be increased when Ridogrel is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Ridogrel is combined with (S)-Warfarin.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Ridogrel is combined with 4-hydroxycoumarin.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	The risk or severity of bleeding and hemorrhage can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Ridogrel.
Abciximab	The risk or severity of bleeding can be increased when Ridogrel is combined with Abciximab.
Aceclofenac	The risk or severity of bleeding can be increased when Aceclofenac is combined with Ridogrel.
Acemetacin	The risk or severity of bleeding can be increased when Acemetacin is combined with Ridogrel.
Acenocoumarol	The risk or severity of bleeding can be increased when Ridogrel is combined with Acenocoumarol.
Acetylsalicylic acid	Acetylsalicylic acid may increase the antiplatelet activities of Ridogrel.
Alaproclate	The risk or severity of hemorrhage can be increased when Alaproclate is combined with Ridogrel.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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

Property	Value	Source
logP	4.3	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00839 mg/mL	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 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	88.89 m³·mol^-1	ChemAxon
Polarizability	34.94 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

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 inhibitor	Non-inhibitor	0.6234
CYP450 2D6 inhibitor	Non-inhibitor	0.839
CYP450 2C19 inhibitor	Non-inhibitor	0.5103
CYP450 3A4 inhibitor	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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 derivativesCarbonyl compounds / Alkyl fluorides
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

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1700	N/A	N/A	8289199 / 8831771 / 10197967
IC 50 (nM)	2100	N/A	N/A	7932586
IC 50 (nM)	5200	N/A	N/A	8289199
Kd (nM)	8000	N/A	N/A	9876106

Details1. Thromboxane A2 receptor

Kind: Protein
Organism: Humans
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

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
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]
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]
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]
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]
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]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	14.7	N/A	N/A	9876106
IC 50 (nM)	3	N/A	N/A	1447738
IC 50 (nM)	4	N/A	N/A	8289199 / 10197967
IC 50 (nM)	7	N/A	N/A	8831771
IC 50 (nM)	8	N/A	N/A	8289199

Details2. Thromboxane-A synthase

Kind: Protein
Organism: Humans
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

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]
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]
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]
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]
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]
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 December 02, 2019 05:45

Ridogrel

Identification

Structure for Ridogrel (DB01207)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References