81846-19-7

Basic information

• Product Name: REMODULIN
• Synonyms: 2-[[[(1R,2R,3aS,9aS)-2α-Hydroxy-1β-[(S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-benzo[f]indene]-5-yl]oxy]acetic acid;UT-15;[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid;[1R-[1α(S*),2β,3aα,9aα]]-;2-[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic Acid;Acetic acid, 2-[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]-;Treprostinil Sodium intermediate;REMODULIN
• CAS NO: 81846-19-7
• Molecular Formula: C₂₃H₃₄O₅
• Molecular Weight: 390.51
• EINECS: 1592732-453-0
• Product Categories: Aromatics;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 81846-19-7.mol
• Article Data: 22

Chemical Properties

• Melting Point: 121-123°
• Boiling Point: 587.1 °C at 760 mmHg
• Flash Point: 199.3 °C
• Appearance: /
• Density: 1.158 g/cm³
• Vapor Pressure: 1.25E-14mmHg at 25°C
• Refractive Index: 1.553
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Chloroform (Slightly, Heated), Methanol (Slightly, Heated)
• PKA: 3.19±0.10(Predicted)
• CAS DataBase Reference: REMODULIN(CAS DataBase Reference)
• NIST Chemistry Reference: REMODULIN(81846-19-7)
• EPA Substance Registry System: REMODULIN(81846-19-7)

Safety Data

• Hazardous Substances Data: 81846-19-7(Hazardous Substances Data)

Usage

Uses

Synthetic analog of Prostacyclin (P839060). Antihypertensive. Treprostinil, marketed under the trade name Remodulin is a medication used to treat pulmonary arterial hypertension (PAH).

Pharmacokinetics

Treprostinil is rapidly absorbed from the subcutaneous site of infusion, with an almost 100% bioavailability and a mean half-life of 85 minutes (34 minutes for the IV infusion). The IV solution must be diluted with normal saline or sterile water before starting the infusion. Unlike epoprostenol, treprostinil is stable at room temperature for up to 5 years, with vasodilation action lasting from 4 to 6 hours, compared with the short, 2- to 3-minute action for epoprostenol. Because of its long life in the body, it can be administered under the skin with a microinfusion subcutaneous infusion pump rather than into the bloodstream and, thus, without hospitalization, as contrasted with the central IV infusion of epoprostenol.

Clinical Use

Treprostinil is a synthetic, stable form of prostacyclin for the treatment for advanced pulmonary hypertension with NYHA class III or IV symptoms as well as for late-stage peripheral vascular disease (PVD). Its sodium salt injectable form is administered either as a continuous subcutaneous infusion directly into the skin or, if the subcutaneous infusion is not tolerated, as a continuous IV infusion without an implanted catheter.

Side effects

Side effects include jaw pain, headaches, nausea, diarrhea, flushing, and localized pain at the delivery site under the skin. This pain has been reported as slight to severe irritation. Patients using the drug seem to ex-perience improvement in their condition, including decreased fatigue, decreased shortness of breath, and decreased pulmonary artery pressures, as well as overall improvement in quality of life.

InChI:InChI=1/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1

Upstream product

• 1425937-58-1 (R)-1-(3-(benzyloxy)benzyl)-5-oxo-3-(tert-butyldimethylsilyloxy)cyclopentene 
• 1257983-83-7 (1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-1-((3S,1E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalene-2,5-diol 
• 1425937-49-0 ((1S,2S,3R,4R)-2-(3-hydroxybenzyl)-4-(tert-butyldimethylsilyloxy)-3-((3S,1E)-3-(tert-butyldimethylsilyloxy)oct-1-enyl)cyclopentyl)methyl methanesulfonate 
• 1425937-47-8 ((1S,2S,3R,4R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)-3-((3S,1E)-3-(tert-butyldimethylsilyloxy)oct-1-enyl)cyclopentyl)methyl 4-methylbenzenesulfonate 
• 1425937-46-7 ((1S,2S,3R,4R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)-3-((3S,1E)-3-(tert-butyldimethylsilyloxy)oct-1-enyl)cyclopentyl)methyl methanesulfonate 
• 1425937-44-5 ((1S,2S,3R,4R)-2-(3-(benzyloxy)benzyl)-4-(tert-butyldimethylsilyloxy)-3-((3S,1E)-3-(tert-butyldimethylsilyloxy)oct-1-enyl)cyclopentyl)methanol 
• 1425937-43-4 (1R,2R,3R)-3-(3-(benzyloxy)benzyl)-2-((3S,1E)-3-hydroxyoct-1-enyl)-4-methylenecyclopentanol 
• 91842-31-8 (1E)-tributyl-stannyl-(3S)-tert-butyldimethylsilyloxyoctene 
• 1425937-41-2 ((3S,1E)-1-((1R,2R,5R)-2-(3-(benzyloxy)benzyl)-3-methylene-5-(tert-butyldimethylsilyloxy)cyclopentyl)oct-1-en-3-yloxy)(tert-butyl)dimethylsilane 
• 1425937-39-8 (2R,3R,4R)-2-(3-(benzyloxy)benzyl)-4-triethylsilyloxy-3-((3S,1E)-3-triethylsilyloxyoct-1-enyl)cyclopentanone 
• 1425937-59-2 (3R)-1-[3-(benzyloxy)benzyl]-5-oxo-3-(triethylsilyloxy)cyclopent-1-ene 
• 183073-00-9 (1S,2E)-1-pentyl-3-(1,1,1-tributylstannyl)-2-propenyl (1,1,1-triethylsilyl) ether 
• 1425937-52-5 (1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyloxy)-1-((3S,1E)-3-(tert-butyldimethylsilyloxy)oct-1-enyl)-1H-cyclopenta[b]naphthalen-5-ol 
• 1425937-50-3 ((1S,2S,3R,4R)-2-(3-hydroxybenzyl)-4-(tert-butyldimethylsilyloxy)-3-((3S,1E)-3-(tert-butyldimethylsilyloxy)oct-1-enyl)cyclopentyl)methyl 4-methylbenzenesulfonate 

Downstream Products

• 1355990-07-6 2-((1R,2R,3aS,9aS)-2-hydroxy-1-(S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-5-yloxylacetic acid ethyl ester 
• 1422975-19-6 C₃₇H₅₇NO₇S 
• 81845-98-9 2-((1R,2R,3aS,9aS)-2-hydroxy-1-(S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-5-yloxylacetic acid methyl ester 

Relevant articles and documents

EFFICIENT CRYSTALLIZATION PROCESS FOR PREPARING ULTRAPURE TREPROSTINIL AND CRYSTAL PREPARED THEREFROM

There is provided a crystalline Form I of anhydrous Treprostinil and processes for the preparation thereof. The crystalline Form I of anhydrous Treprostnil is a stable crystalline form, which can provide steady physicochemical properties for pharmaceutical formulations, and is advantageous widely and safety used in storage, shipment, and handling for commercially considerations.

Synthetic routes to treprostinil N-acyl methylsulfonamide

The synthesis of the prodrug candidate, treprostinil N-acyl methylsulfonamide 5 was accomplished from treprostinil 2 utilising protecting group strategies. A more direct synthesis for the prodrug was also achieved using a treprostinil triol precursor 12 and bromoacetyl acylmethylsulfonamide 14. The overall yield of treprostinil N-acyl sulfonamide 5 directly from the triol precursor 12 is similar to the protecting group strategies because deprotonation of the acidic proton in the bromoacetyl acylmethylsulfonamide 14 reduces electrophilicity. However, the more direct route using the treprostinil triol precursor holds greater promise as a strategy to prepare a wide range of treprostinil prodrug candidates. Treprostinil N-acyl methylsulfonamide prodrug 5 exhibited a 30-fold decrease in the potency at the human prostacyclin (IP) receptor compared to treprostinil 2 in an in vitro cyclic AMP assay.

Process for Preparing Treprostinil

The present invention relates to a synthesis method of treprostinil, and more specifically, to a method of synthesizing high-purity treprostinil in an economical and efficient manner; and to high-purity treprostinil crystals synthesized by the method. According to the synthesis method of the present invention, treprostinil having a purity of 99.9% or more can be produced in an economical and efficient manner.COPYRIGHT KIPO 2017