| Company Name: |
Nuray Chemicals Pvt Ltd
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| Tel: |
+91-4066616700 +91-8220444745 |
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info@nuraychemicals.com |
| Products Intro: |
Product Name:Treprostinil sodium
Purity:98% Package:1 kg,5 kg, 10 kg,25kg
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| Company Name: |
Angel Bio Pharma
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| Tel: |
08069013898Ext 347 |
| Email: |
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| Products Intro: |
Product Name:Treprostinil Sodium
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| Company Name: |
SS PHARMA LLC
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| Tel: |
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| Email: |
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| Products Intro: |
Product Name:TREPROSTINIL SODIUM
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| | TreprostinilSodium Basic information |
| | TreprostinilSodium Chemical Properties |
| | TreprostinilSodium Usage And Synthesis |
| Description | Treprostinil sodium has been launched for the treatment of pulmonary hypertension.
This synthetically designed tricyclic benzindene analog of the natural potent vasodilator
prostacyclin has been developed for subcutaneous infusion. Treprostinil sodium can be
prepared in a 15 step stereoselective process. It has been suggested that treprostinil
sodium acts via the prostacyclin receptor since the agent could only increase CAMP in
human embryonic kidney cells transiently transfected with the human prostacyclin
receptor. In a conscious spontaneously hypertensive rat model, treprostinil sodium
reduced hypoxia-induced increases in pulmonary arterial pressure and pulmonary vascular
resistance in a dose-related manner. At higher doses, the test compound reduced
systemic arterial pressure and systemic vascular resistance. In patients with primary
pulmonary arterial hypertension, a one year therapy with treprostinil improved
hemodynamics parameters: a 22% improvement in cardiac output, a 24% significant
decrease in peripheral vascular resistance, a decrease in mean pulmonary arterial
pressure (55 vs. 58 mmHg at baseline) and an improvement in NYHA functional class
were observed. In addition, 6-min walk distance was significantly improved (463 vs. 399 m
at baseline). A larger study conducted in 470 patients with pulmonary arterial hypertension
has demonstrated the same type of result. In patients with severe intermittent claudication,
infusion of treprostinil was well tolerated and increased the blood flow in most of the
peripheral arteries of the lower limb. Treprostinil is eliminated in a biphasic distribution with
a terminal half-life of 2-4 h. Approximately 79% of the administrated dose is excreted in the
urine. Thus, treprostinil, in contrast to the currently available epoprostenol remains
biologically active for a longer time and is not sensitive to light and temperature. Moreover,
the subcutaneous administration avoids the epoprostenol systemic side effects due to
continuous surgically implanted intravenous infusion. Treprostinil is well tolerated by
patients and the main adverse effects currently observed are injection site reaction and
injection site pain. | | Originator | Pharmacia/
GSK (USA) | | Uses | Treprostinil Sodium is a potent agonist of DP1, EP2 and IP receptors. | | Brand name | Remodulin | | Synthesis | The synthesis of treprostinil starts from commercially available 3-methoxybenzyl
alcohol (213). The hydroxyl group in 213 was protected as a
t-butyldimethylsilyl ether via reaction with TBDMS
chloride in DCM at rt. A regiospecific introduction of the
allylic chain and deprotection of the silyl group in situ
provided alcohol 216 in 36% yield in a three-step sequence.
Swern oxidation of alcohol 216 using oxalyl
chloride/DMSO furnished aldehyde 217 in 86% yield.
Acetylene 218 was first treated with magnesium ethyl
bromide and then reacted with aldehyde 217 to provide
adduct 219 in 52% yield. The alcohol functional group in 219 was then transformed into a carbonyl group in 220 via a
PCC-mediated oxidation. Ketone 220 was then reduced
again using chiral boron reagent to give the chiral alcohol
which was protected with TBDMS chloride in situ (221).
Optically pure intermediate 221 underwent cobalt-mediated
Pauson-Khand reaction to furnish tricyclic compound 222 in
excellent yield. Catalytic hydrogenation was employed to
reduce the double bond and the hydroxyl moiety to give
ketone 223. Sodium borohydride mediated reduction of the
carbonyl group in 223 gave single diastereomer 224. The
THP and methyl ether protecting groups were then removed
in a two-step process to give triol 226. The more reactive
hydroxyl group on the phenyl ring was then reacted with
chloroacetonitrile to furnish nitrile 227. A base mediated
hydrolysis of the nitrile provided free acid, treprostinil
(228), which was converted to its sodium salt 26 by titration
with sodium hydroxide (no yield reported). 
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| | TreprostinilSodium Preparation Products And Raw materials |
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