Page last updated: 2024-11-12

azd 0837

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

AZD 0837: anticoagulant prodrug of AR-H067637 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	9961205
CHEMBL ID	4297593
SCHEMBL ID	9914214
MeSH ID	M0549199

Synonyms (22)

Synonym
atecegatran fexenetil
atecegatran fexenetil [inn]
4gu1d587jv ,
azd 0837
atecegatran metoxil
atecegatran metoxil [inn]
2-azetidinecarboxamide, 1-((2r)-(3-chloro-5- (difluoromethoxy)phenyl)hydroxyacetyl)-n-((4-(imino(methoxyamino)methyl)phenyl)methyl)-, (2s)-
azd0837
unii-4gu1d587jv
azd 0837 [who-dd]
2-azetidinecarboxamide, 1-((2r)-(3-chloro-5-(difluoromethoxy)phenyl)hydroxyacetyl)-n-((4-(imino(methoxyamino)methyl)phenyl)methyl)-, (2s)-
(2s)-1-((2r)-2-(3-chloro-5-(difluoromethoxy)phenyl)-2-hydroxyacetyl)-n-((4-((z)-n'-methoxycarbamimidoyl)phenyl)methyl)azetidine-2-carboxamide
2-azetidinecarboxamide, 1-((2r)-2-(3-chloro-5-(difluoromethoxy)phenyl)-2-hydroxyacetyl)-n-((4-(imino(methoxyamino)methyl)phenyl)methyl)-, (2s)-
atecegatran metoxil [who-dd]
SCHEMBL9914214
DB12507
CHEMBL4297593
(2s)-1-[(2r)-2-[3-chloro-5-(difluoromethoxy)phenyl]-2-hydroxyacetyl]-n-[[4-[(e)-n'-methoxycarbamimidoyl]phenyl]methyl]azetidine-2-carboxamide
(2s)-1-[(2r)-2-[3-chloro-5-(difluoromethoxy)phenyl]-2-hydroxyacetyl]-n-[[4-[(z)-n'-methoxycarbamimidoyl]phenyl]methyl]azetidine-2-carboxamide
HY-10273
CS-0002522
AKOS040750618

Research Excerpts

Toxicity

Excerpt	Reference	Relevance
" A numerically higher incidence of serious adverse events was observed with 350mg bid AZD0837 compared with 150mg bid, with six of 13 being cardiac related, all with different diagnoses."	( Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Jensen, E; Olsson, SB; Panfilov, S; Rasmussen, LH; Tveit, A; Wåhlander, K; Wessman, P, 2010)	0.36

Bioavailability

Excerpt	Reference	Relevance
"AZD0837 was rapidly absorbed, with a mean oral bioavailability of 22 - 52%, and bioconverted to the active form, AR-H067637."	( Single-dose pharmacokinetics, pharmacodynamics and safety of AZD0837, a novel oral direct thrombin inhibitor, in young healthy male subjects. Cullberg, M; Dunér, K; Elg, M; Eriksson, UG; Jensen, E; Johansson, S; Wåhlander, K; Wollbratt, M, 2011)	0.37
" Bioavailability over the gut-wall was estimated to be high in duodenum (70%) compared to the small intestine (25%)."	( A semi-mechanistic modeling strategy for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations. Bergstrand, M; Eriksson, UG; Karlsson, MO; Söderlind, E; Weitschies, W, 2012)	0.38

Dosage Studied

Excerpt	Relevance	Reference
" Concomitant dosing with ketoconazole increased the area under the plasma concentration-time curve for AZD0837 (by 99%) and for AR-H067637 (by 51%)."	( Effects of ketoconazole on the in vivo biotransformation and hepatobiliary transport of the thrombin inhibitor AZD0837 in pigs. Bottner, P; Eriksson, UG; Knutson, L; Lennernäs, H; Lundahl, A; Matsson, EM; Palm, JE, 2011)	0.37

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (19)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (5.26)	29.6817
2010's	17 (89.47)	24.3611
2020's	1 (5.26)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	7 (36.84%)	5.53%
Reviews	5 (26.32%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	7 (36.84%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
beta-alanine [no description available]	4.1	2	0	amino acid zwitterion; beta-amino acid	agonist; fundamental metabolite; human metabolite; inhibitor; neurotransmitter
chlorine chloride : A halide anion formed when chlorine picks up an electron to form an an anion.	2.05	1	0	halide anion; monoatomic chlorine	cofactor; Escherichia coli metabolite; human metabolite
dalteparin Dalteparin: A low-molecular-weight fragment of heparin, prepared by nitrous acid depolymerization of porcine mucosal heparin. The mean molecular weight is 4000-6000 daltons. It is used therapeutically as an antithrombotic agent. (From Merck Index, 11th ed)	2.05	1	0
methanol Methanol: A colorless, flammable liquid used in the manufacture of FORMALDEHYDE and ACETIC ACID, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness.. primary alcohol : A primary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has either three hydrogen atoms attached to it or only one other carbon atom and two hydrogen atoms attached to it.. methanol : The primary alcohol that is the simplest aliphatic alcohol, comprising a methyl and an alcohol group.	2.07	1	0	alkyl alcohol; one-carbon compound; primary alcohol; volatile organic compound	amphiprotic solvent; Escherichia coli metabolite; fuel; human metabolite; mouse metabolite; Mycoplasma genitalium metabolite
cimetidine Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.. cimetidine : A member of the class of guanidines that consists of guanidine carrying a methyl substituent at position 1, a cyano group at position 2 and a 2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl group at position 3. It is a H2-receptor antagonist that inhibits the production of acid in stomach.	3.44	1	1	aliphatic sulfide; guanidines; imidazoles; nitrile	adjuvant; analgesic; anti-ulcer drug; H2-receptor antagonist; P450 inhibitor
ketoconazole 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.	3.86	2	1	dichlorobenzene; dioxolane; ether; imidazoles; N-acylpiperazine; N-arylpiperazine
thiophenes Thiophenes: A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.. thiophenes : Compounds containing at least one thiophene ring.	3.16	1	0	mancude organic heteromonocyclic parent; monocyclic heteroarene; thiophenes; volatile organic compound	non-polar solvent
thiazoles [no description available]	3.16	1	0	1,3-thiazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene
ferric chloride ferric chloride: RN given refers to cpd with MF of Fe-Cl3; used to induce experimental arterial thrombosis to evaluate antithrombotic agents	2.05	1	0	iron coordination entity	astringent; Lewis acid
dabigatran Dabigatran: A THROMBIN inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic EMBOLISM in patients with nonvalvular atrial fibrillation.. dabigatran : An aromatic amide obtained by formal condensation of the carboxy group of 2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazole-5-carboxylic acid with the secondary amoino group of N-pyridin-2-yl-beta-alanine. The active metabolite of the prodrug dabigatran etexilate, it acts as an anticoagulant which is used for the prevention of stroke and systemic embolism.	4.72	3	0	aromatic amide; benzimidazoles; beta-alanine derivative; carboxamidine; pyridines	anticoagulant; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; EC 3.4.21.5 (thrombin) inhibitor
vitamin k semiquinone radical vitamin K semiquinone radical: found in active preparations of vitamin K-dependent carboxylase. vitamin K : Any member of a group of fat-soluble 2-methyl-1,4-napthoquinones that exhibit biological activity against vitamin K deficiency. Vitamin K is required for the synthesis of prothrombin and certain other blood coagulation factors.	6.55	4	2
ximelagatran ximelagatran: prodrug (via hydroxylation) of melagatran & a direct thrombin inhibitor; liver toxicity concerns so AZD0837 being developed to replace this. ximelagatran : A member of the class of azetidines that is melagatran in which the carboxylic acid group has been converted to the corresponding ethyl ester and in which the amidine group has been converted into the corresponding amidoxime. A prodrug for melagatran, ximelagatran was the first orally available direct thrombin inhibitor to be brought to market as an anticoagulant, but was withdrawn in 2006 following reports of it causing liver damage.	5.77	3	1	amidoxime; azetidines; carboxamide; ethyl ester; hydroxylamines; secondary amino compound; secondary carboxamide; tertiary carboxamide	anticoagulant; EC 3.4.21.5 (thrombin) inhibitor; prodrug; serine protease inhibitor
rivaroxaban Rivaroxaban: A morpholine and thiophene derivative that functions as a FACTOR XA INHIBITOR and is used in the treatment and prevention of DEEP-VEIN THROMBOSIS and PULMONARY EMBOLISM. It is also used for the prevention of STROKE and systemic embolization in patients with non-valvular ATRIAL FIBRILLATION, and for the prevention of atherothrombotic events in patients after an ACUTE CORONARY SYNDROME.. rivaroxaban : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-chlorothiophene-2-carboxylic acid with the amino group of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one. An anticoagulant used for prophylaxis of venous thromboembolism in patients with knee or hip replacement surgery.	3.16	1	0	aromatic amide; lactam; monocarboxylic acid amide; morpholines; organochlorine compound; oxazolidinone; thiophenes	anticoagulant; EC 3.4.21.6 (coagulation factor Xa) inhibitor
apixaban [no description available]	3.16	1	0	aromatic ether; lactam; piperidones; pyrazolopyridine	anticoagulant; EC 3.4.21.6 (coagulation factor Xa) inhibitor
edoxaban edoxaban : A monocarboxylic acid amide that is used (as its tosylate monohydrate) for the treatment of deep vein thrombosis and pulmonary embolism.	3.16	1	0	chloropyridine; monocarboxylic acid amide; tertiary amino compound; thiazolopyridine	anticoagulant; EC 3.4.21.6 (coagulation factor Xa) inhibitor; platelet aggregation inhibitor
methylcellulose Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative.	3.46	1	1
warfarin Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.. warfarin : A racemate comprising equal amounts of (R)- and (S)-warfarin. Extensively used as both an anticoagulant drug and as a pesticide against rats and mice.. 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one : A member of the class of coumarins that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenyl-3-oxo-1-butyl group.	5.76	3	1	benzenes; hydroxycoumarin; methyl ketone

Condition	Indicated	Relationship Strength	Studies	Trials
Apoplexy [description not available]	0	7.33	6	3
Auricular Fibrillation [description not available]	0	7.73	7	4
Cardiovascular Stroke [description not available]	0	3	1	0
Atrial Fibrillation Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.	1	9.73	7	4
Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).	0	3	1	0
Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)	0	7.33	6	3
Embolus [description not available]	0	5.62	3	2
Embolism Blocking of a blood vessel by an embolus which can be a blood clot or other undissolved material in the blood stream.	0	5.62	3	2
Bleeding [description not available]	0	3.85	2	1
Hemorrhage Bleeding or escape of blood from a vessel.	0	3.85	2	1
Deep Vein Thrombosis [description not available]	0	2.05	1	0
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	0	2.05	1	0
Blood Clot [description not available]	0	3.85	2	1
Thrombosis Formation and development of a thrombus or blood clot in the blood vessel.	0	3.85	2	1
Venous Thrombosis The formation or presence of a blood clot (THROMBUS) within a vein.	0	2.05	1	0
Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.	0	2.98	1	0
Acute Coronary Syndrome An episode of MYOCARDIAL ISCHEMIA that generally lasts longer than a transient anginal episode that ultimately may lead to MYOCARDIAL INFARCTION.	0	2.98	1	0

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