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 which acts as an inhibitor of platelet aggregation and is recommended for the treatment of peripheral vascular diseases. The compound was shown to be a potent agonist at PGE2-sensitive and prostacyclin-sensitive receptors in animal studies. Iloprost is administered by IV infusion and has been reported to have beneficial effects in Buerger's and Raynaud's diseases as well as peripheral artery occlusive disease.

Chemical Properties

Different sources of media describe the Chemical Properties of 78919-13-8 differently. You can refer to the following data:
1. Colourless Oil
2. Quinone exists as a large, yellow, monoclinic prism with an irritating odor. Quinone is extensively used in the dye, textile, chemical, tanning, and cosmetic industries. In chemical synthesis for hydroquinone and other chemicals, quinone is used as an intermediate. It is also used in the manufacturing industries and chemical laboratories associated with protein fi ber, photographic fi lm, hydrogen peroxide, and gelatin making.

Uses

A synthetic analogue of Prostacyclin (PGI2) used to treat pulmonary arterial hypertension (PAH), scleroderma, Raynaud's phenomenon and ischemia. It acts through elevation of cAMP by binding to the prostacyclin receptor (IP receptor). Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets with an ED50 of about 13 nM. In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time.

Definition

ChEBI: A carbobicyclic compound that is prostaglandin I2 in which the endocyclic oxygen is replaced by a methylene group and in which the (1E,3S)-3-hydroxyoct-1-en-1-yl side chain is replaced by a (3R /stereo>)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl group. A synthetic analogue of prostacyclin, it is used as the trometamol salt (generally by intravenous infusion) for the treatment of peripheral vascular disease and pulmonary hypertension.

Brand name

Ventavis (Schering);Iiomedin.

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

• 17814-85-6 (4-carboxybutyl)triphenylphosphonium bromide 
• 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 
• 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 
• 74818-68-1 (3aS,5R,6aR)-4-[(E)-(S)-4-Methyl-3-(tetrahydro-pyran-2-yloxy)-oct-1-en-6-ynyl]-5-(tetrahydro-pyran-2-yloxy)-hexahydro-pentalen-2-one 
• 74818-49-8 (3aS,5R,6aR)-5-Hydroxy-4-((E)-(S)-3-hydroxy-4-methyl-oct-1-en-6-ynyl)-hexahydro-pentalen-2-one 
• 41723-91-5 4-carboxybutyliden triphenylphosphorane sodium 
• 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 
• 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 
• 126436-91-7 5-[(3aS,4R,5R,6aS)-5-(tert-Butyl-dimethyl-silanyloxy)-4-((E)-(S)-3-hydroxy-4-methyl-oct-1-en-6-ynyl)-hexahydro-pentalen-(2E)-ylidene]-pentanoic acid 
• 871095-04-4 (3aS,4S,5R,6aR)-5-((tert-butyldimethylsilyl)oxy)-4-(hydroxymethyl)hexahydropentalen-2(1H)-one 
• 32233-40-2 (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one 
• 70073-58-4 dimethyl (2-oxo-3-methylhept-5-ynyl)-phosphonate 
• 116484-93-6 (+/-)-2-methylhex-4-ynoic acid ethyl ester 
• 182809-41-2 diethyl 2-(but-2-yn-1-yl)-2-methylmalonate 

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.