35121-78-9

Usage

Uses

Used in Pharmaceutical Industry:
Epoprostenol is used as an inhibitor (platelet) for managing conditions that involve abnormal blood clotting or high blood pressure in the arteries of the lungs (pulmonary arterial hypertension). It helps to prevent blood clot formation and dilates blood vessels, improving blood flow and reducing the workload on the heart.
Used in Cardiovascular Applications:
In the cardiovascular field, Epoprostenol is used as a vasodilator to treat pulmonary arterial hypertension. It works by relaxing the smooth muscle cells in the walls of blood vessels, leading to the widening of the blood vessels and a subsequent decrease in blood pressure.
Used in Hematology:
Epoprostenol is utilized as an antiplatelet agent in the field of hematology, particularly for patients with conditions that increase the risk of blood clot formation, such as sickle cell disease or those undergoing procedures that may cause clotting issues.
Used in Critical Care Medicine:
In critical care medicine, Epoprostenol is used as a therapeutic agent for patients with severe pulmonary hypertension, as it can help to improve oxygenation and reduce the strain on the right side of the heart.
Used in Research and Development:
Epoprostenol is also used in research and development for the study of prostaglandins and their role in various physiological processes, as well as for the development of new medications with similar or improved properties.

Originator

Prostacyclin,ZYF Pharm Chemical

Manufacturing Process

Preparation of prostacyclin:Pig aortas were stripped of adventitia, snap frozen in liquid nitrogen, crushed into a fine powder, resuspended in 0.05 M Tris buffer (pH 7.5) (1:4, w:v) andhomogenised at high speed in a Polytron (KIMENATIC, LUCERNE, SWITZERLAND) homogenizer. The homogenate was centrifuged for 15 min and the resulting supernatant centrifuged again for 5 min. The pellet was discarded, while the pellet obtained after centrifugation of the supernatant was resuspended in deionized water and lyophilized. An average yield of 150 mg of aortic microsomal powder (51% protein) per 100 g of aortic tissue was obtained.

Therapeutic Function

Platelet aggregation inhibitor, Antimetastatic

InChI:InChI=1/C20H32O5/c1-2-3-4-7-14(21)10-11-16-17-12-15(8-5-6-9-20(23)24)25-19(17)13-18(16)22/h8,10-11,14,16-19,21-22H,2-7,9,12-13H2,1H3,(H,23,24)/b11-10+,15-8-/t14-,16+,17?,18+,19?/m0/s1

Upstream product

• 42935-17-1 9,11-Epidioxy-15-hydroxy-5,13-icosadiensaeure 
• 149-73-5 trimethyl orthoformate 
• 78824-82-5 11,15-O-bis(tert-butyldimethylsilyl)PGI₂ methyl ester 
• 59926-53-3 5,6-didehydro-11,15-O-bis(tert-butyldimethylsilyl)PGF_2α methyl ester 
• 61799-74-4 PGI₂ methyl ester 

Downstream Products

• 58962-34-8 7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-6-oxo-heptanoic acid 

Relevant academic research and scientific papers

A SHORT WAY TO PROSTACYCLIN

A facile, stereospecific preparation of prostacyclin has been accomplished starting from a 5,6-dehydroprostaglandin F2α derivative.

THERAPY FOR COMPLICATIONS OF DIABETES

A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

ANTIHYPERTENSIVE THERAPY

A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.

Method for treating resistant hypertension

A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.

Prodrug derivatives of carboxylic acid drugs

Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.

Method for preparing 10,10-difluoro prostacyclin intermediates and new compounds produced thereby

A method is provided for preparing intermediates for use in 10,10-difluoro prostacyclin syntheses which method includes the steps of aceylating ketopinic acid or its acid halide to form the corresponding ketopinoyl diene ester intermediate, subjecting the diene ester to a Diels-Alder reaction by reacting same with cyclopentendione, subjecting the resulting chiral ester intermediate to a fluorination and reduction to form the corresponding chiral ester diol intermediate, subjecting the diol to solvolysis to form the chiral triol intermediate, hydroxylating the chiral triol to form a pentol intermediate, subjecting the pentol to a ring cleavage to form the difluoro dihydroxy prostacyclin intermediate STR1 and subjecting same to a Wittig reaction to form the difluoro dihydroxy prostacyclin intermediate STR2 All of the above-mentioned intermediates are novel compounds and thus are also provided.

Pharmaceutical combination

Combinations comprising an anti-aggregatory substance together with one or more of an anti-oxidant and a thromboxane A2 synthetase inhibitor are disclosed. Combinations are useful for the treatment/prophylaxis of disorders attributable to blood platelet aggregation.