78919-13-8

Basic information

• Product Name: ILOPROST
• Synonyms: (16r,s)-methyl-18,18,19,19-tetradehydro-6a-carbaprostaglandini(sub2);1h)-pentalenylidene)-;pentanoicacid,5-(hexahydro-5-hydroxy-4-(3-hydroxy-4-methyl-1-octen-6-ynyl)-2(;zk36374;6,9ALPHA-METHYLENE-11ALPHA,15S-DIHYDROXY-16-METHYL-PROSTA-5E,13E-DIEN-18-YN-1-OIC ACID;CILOPROST;5-[Hexahydro-5-hydroxy-4-(3-hydroxy-4-methyl-1-octen-6-ynyl)-2(1H)-pentalenylidene]pentanoic acid;Endoprost
• CAS NO: 78919-13-8
• Molecular Formula: C22H32O4
• Molecular Weight: 360.49
• Product Categories: Chiral Reagents;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 78919-13-8.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 539.2oC at 760 mmHg
• Flash Point: 294oC
• Appearance: colorless oil
• Density: 1.21g/cm3
• Vapor Pressure: 7.06E-14mmHg at 25°C
• Refractive Index: 1.629
• Storage Temp.: Desiccate at -20°C
• Solubility: Soluble in methyl acetate
• PKA: 4.77±0.10(Predicted)
• CAS DataBase Reference: ILOPROST(CAS DataBase Reference)
• NIST Chemistry Reference: ILOPROST(78919-13-8)
• EPA Substance Registry System: ILOPROST(78919-13-8)

Safety Data

• Hazardous Substances Data: 78919-13-8(Hazardous Substances Data)

Usage

Description

Iloprost is a stable epoprostenol derivative, a synthetic analogue of Prostacyclin (PGI2), which acts as an inhibitor of platelet aggregation. It is a carbobicyclic compound with unique structural features that make it a potent agonist at PGE2-sensitive and prostacyclin-sensitive receptors. Iloprost is administered by intravenous infusion and has been reported to have beneficial effects in various diseases.

Uses

Used in Pharmaceutical Industry:
Iloprost is used as a therapeutic agent for the treatment of pulmonary arterial hypertension (PAH), scleroderma, Raynaud's phenomenon, and ischemia. It acts through the elevation of cAMP by binding to the prostacyclin receptor (IP receptor), which helps in managing these conditions.
Used in Cardiovascular Applications:
Iloprost is used as a vasodilator, hypotensive, and antidiuretic agent, which aids in the treatment of peripheral vascular diseases. It has been reported to have beneficial effects in Buerger's and Raynaud's diseases, as well as peripheral artery occlusive disease.
Used in Hemostasis Regulation:
Iloprost is used as an inhibitor of platelet aggregation, with an ED50 of about 13 nM for ADP, thrombin, and collagen-induced aggregation of human platelets. This property helps in preventing excessive clotting and maintaining proper blood flow.
Brand Names:
Ventavis (Schering) and Iiomedin are some of the brand names under which Iloprost is marketed for its various applications.

Health Hazard

Exposures to quinine vapor are highly irritating to the eyes and may be followed by corneal opacities, structural changes in the cornea, and loss of vision. Solid quinone may produce discoloration, severe irritation, swelling, and form papules and vesicles.

Biological Activity

Prostacyclin (PGI 2 ) analog that binds with high affinity to IP, EP 1 and EP 3 receptors (K i values are 11, 11, 56, 284, 619, 1035, 1870 and 6487 nM for IP, EP 1 , EP 3 , EP 4 , FP, DP, EP 2 and TP receptors respectively). Inhibits platelet aggregation induced by collagen, thrombin and ADP (IC 50 values are 0.24, 0.71 and 1.07 nM respectively).

Biochem/physiol Actions

Iloprost is used to treat children with PH (pulmonary hypertension) after the surgery to clear CHD (congenital heart disease). In transplant patients, this prostacyclin analogue is used to inhibit renal dysfunction. Iloprost performs various functions like vasodilatation and cytoprotection. It has higher stability than prostacyclin.

InChI:InChI=1/C22H32O4/c1-3-4-7-15(2)20(23)11-10-18-19-13-16(8-5-6-9-22(25)26)12-17(19)14-21(18)24/h8,10-11,15,17-21,23-24H,5-7,9,12-14H2,1-2H3,(H,25,26)/b11-10+,16-8+/t15?,17-,18?,19-,20+,21+/m0/s1

Upstream product

• 117624-93-8 (1S,5R,6R,7R)-6-<<(tert-butyldimethylsilyl)oxy>methyl>-7-<(tert-butyldimethylsilyl)oxy>-2-oxabicyclo<3.3.0>octane-3-one 
• 104172-98-7 (3aS,4S,5R,6aR)-5-((tert-butyldimethylsilyl)oxy)-4-(((tert-butyldimethylsilyl)oxy)methyl)hexahydropentalen-2(1H)-one 
• 871095-04-4 (3aS,4S,5R,6aR)-5-((tert-butyldimethylsilyl)oxy)-4-(hydroxymethyl)hexahydropentalen-2(1H)-one 
• 1202227-23-3 (3S,E)-1-((3aS,4R,5R,6aR)-5-((tert-butyldimethylsilyl)oxy)-5',5'-dimethylhexahydro-1H-spiro[pentalene-2,2'-[1,3]dioxan]-4-yl)-4-methyloct-1-en-6-yn-3-ol 
• 79812-95-6 (3aS,4R,5R,6aR)-5-hydroxy-4-((3S,E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl)hexahydropentalen-2(1H)-one 
• 1202227-32-4 (3aS,4R,5R,6aR)-5-((tert-butyldimethylsilyl)oxy)-4-((3S,E)-3-((tert-butyldimethylsilyl)oxy)-4-methyloct-1-en-6-yn-1-yl)hexahydropentalen-2(1H)-one 
• 182809-41-2 diethyl 2-(but-2-yn-1-yl)-2-methylmalonate 
• 116484-93-6 (+/-)-2-methylhex-4-ynoic acid ethyl ester 
• 70073-58-4 dimethyl (2-oxo-3-methylhept-5-ynyl)-phosphonate 
• 32233-40-2 (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 79745-58-7 5-[(3aS,5R,6aS)-4-[(E)-(S)-4-Methyl-3-(tetrahydro-pyran-2-yloxy)-oct-1-en-6-ynyl]-5-(tetrahydro-pyran-2-yloxy)-hexahydro-pentalen-(2Z)-ylidene]-pentanoic acid 
• 79745-58-7 5-[(3aS,5R,6aS)-4-[(E)-(S)-4-Methyl-3-(tetrahydro-pyran-2-yloxy)-oct-1-en-6-ynyl]-5-(tetrahydro-pyran-2-yloxy)-hexahydro-pentalen-(2E)-ylidene]-pentanoic acid 
• 17814-85-6 (4-carboxybutyl)triphenylphosphonium bromide 
• 146380-17-8 (3aS,4R,5R,6aR)-5-(tert-Butyl-dimethyl-silanyloxy)-4-((E)-(S)-3-hydroxy-4-methyl-oct-1-en-6-ynyl)-hexahydro-pentalen-2-one 

Relevant articles and documents

An alternative synthesis for iloprost via a key bicyclic aldehyde intermediate

An alternative synthesis for iloprost has been accomplished in 14 steps via a convergent synthesis starting from commercially available (?)-Corey lactone diol. The syntheses employ a new and key chiral bicyclic aldehyde (4) intermediate, which is primed for attachment of the required α-side chain and ω-side chain.

PROCESS FOR THE PREPARATION OF ILOPROST

The present invention relates to a process for the preparation of iloprost of formula I through new intermediates, isolation of iloprost of formula I in solid form, as well as preparation of the 16(S)-iloprost and 16(R)-iloprost isomers of formulae (S)-I and (R)-I and isolation of iloprost of formula I and 16(S)-iloprost of formula (S)-I in solid, crystalline form.

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.