Alprostadil

Base Information

• Chemical Name: Alprostadil
• CAS No.: 745-65-3
• Deprecated CAS: 50-83-9,22299-37-2,50865-30-0
• Molecular Formula: C20H34O5
• Molecular Weight: 354.487
• Hs Code.: 29375000
• European Community (EC) Number: 212-017-2
• UNII: F5TD010360
• ChEMBL ID: CHEMBL495
• DSSTox Substance ID: DTXSID9022578
• Metabolomics Workbench ID: 2477
• NCI Thesaurus Code: C28816
• Nikkaji Number: J3.319G
• Pharos Ligand ID: GC3649M152KB
• RXCUI: 598
• Wikidata: Q579348
• Wikipedia: Prostaglandin_E1
• Mol file: 745-65-3.mol

Synonyms:Alprostadil;Caverject;Edex;Lipo PGE1;Lipo-PGE1;Minprog;Muse;PGE1;PGE1alpha;Prostaglandin E1;Prostaglandin E1alpha;Prostavasin;Prostin VR;Prostine VR;Sugiran;Vasaprostan;Viridal

Chemical Property of Alprostadil

Chemical Property:

• Appearance/Colour: Crystalline solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 115-116 °C
• Refractive Index: 1.6120 (estimate)
• Boiling Point: 529.3 °C at 760 mmHg
• PKA: pKa 4.85± 0.07(H2O,t=25±0.1,I=0.1(NaCl)) (Uncertain)
• Flash Point: 288 °C
• PSA: 94.83000
• Density: 1.131 g/cm³
• LogP: 3.47510
• Storage Temp.: −20°C
• Solubility.: ethanol: 1 mg/mL
• Water Solubility.: insoluble
• XLogP3: 3.2
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 13
• Exact Mass: 354.24062418
• Heavy Atom Count: 25
• Complexity: 432

Purity/Quality:

99%min ^*data from raw suppliers

Prostaglandin E1 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, Xi
• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-61
• Safety Statements: 36-26

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CCCCCC(C=CC1C(CC(=O)C1CCCCCCC(=O)O)O)O
• Isomeric SMILES: CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1CCCCCCC(=O)O)O)O
• Recent ClinicalTrials: ALP-1 Continuous Intravenous Infusion to Maintain Clinical Stability in Advanced Heart Failure
• Recent EU Clinical Trials: Phase IIb prospective, unicentric, randomized, parallel, double-blind, placebo-controlled clinical trial to evaluate the intravenous infusion of prostaglandins as therapy in patients with non-arteritic anterior ischemic optic neuropathy.
• Uses: Used for diabetic neuropathy, myocardial infarction, thrombotic vasculitis, arteriosclerosis obliterans, central retinal vein thrombosis. It is used in the treatment of hepatitis cirrhosis, cerebral infarction, diabetes, impotence, respiratory diseases. Liver damage is not serious childA, class B patients, especially patients with antithrombin level childA China effect. For induction of labor, oxytocin, renal insufficiency, treatment mumps, pancreatitis. Injection of prostaglandin E1 is mainly applied to myocardial infarction, heart failure, thrombotic vasculitis, chronic arterial occlusive disease, central retinal vein thrombosis, platelet protection for extracorporeal circulation, arteriography, revascularization surgery. A primary Prostaglandin; easily crystallized from purified biological extracts. Vasodilator (peripheral) Vasodilator;Prostaglandin receptor agonist
• Production method: Sheep seminal vesicles were uesd as raw material for the preparation of PGE crude , with enzyme preparation, incubation, organic solvent extraction, silica gel column separation. The preparation of PGE crude: sheep seminal vesicles [KCl, EDTANa2, PH8] → enzyme suspension [hydroquinone, glutathione] → [arachidonic acid, O2] reaction solution [acetone, ether, methylene chloride] → PGS crude [Separation] → [silica gel] PGE crude Preparation PGE1 finished product: per 1g PGE crude product used 20g silica gel, 10 times the mass of PGE activated silver nitrate silica gel from 200-250 mesh was suspended in expansion agents including: V ethyl acetate : V acetic acid: V petroleum ether: V water = 220: 22.5: 125 : 5 (bp of petroleum ether is 90-120 ℃) , with wet packed column. A small amount of the crude product was dissolved in the same expansion agents, put in the column , eluted. PGE1 and PGE2 were collected . The PGE1 part was put below 35 ℃ to nitrogen concentrating until acetic acid odor was removed, ethyl acetate was added to dissolve, added acid to wash, pH4-5, saline was added to remove silver. The ethyl acetate solution was set in the refrigerator overnight to get finished PGE1 .
• Description: PGE1?(745-65-3) is an endogenous prostaglandin with vasodilatory, anti-platelet, and anti-hypertensive activities.1,2 It is in clinical use for the treatment of erectile dysfunction3 and the emergency management of infants with patent ductus arteriosus4. It has also been used in the treatment of peripheral arterial occlusive disease (PAD).5
• Indications: Alprostadil (prostaglandin E1 [PGE1]; Edex, Topiglan) exerts a number of effects, including systemic vasodilation, inhibition of platelet aggregation, and stimulation of intestinal motility. PGE1 relaxes isolated smooth muscle cells contracted by norepinephrine. It has become widely used in the treatment of ED. Alprostadil binds with PGE receptors and results in a cyclic adenosine monophosphate (cAMP) mediated smooth muscle relaxation. Little is known about the pharmacokinetics of PGE1, but it is believed that as much as 80% is metabolized in one pass through the lungs. Such rapid degradation probably accounts for its lack of significant cardiovascular side effects when administered intracavernosally. PGE1 can also be metabolized in the penis.
• Therapeutic Function: Vasodilator, Abortifacient, Antihypertensive, Bronchodilator
• Biological Functions: Prostaglandin E1 is produced endogenously to relax vascular smooth muscle and cause vasodilation by activating the adenylate cyclase/cAMP pathway. Recent studies show that the cAMP is important in the PGE1 relaxation of penile erectile tissue and vasodilation of penile resistance arteries. Moreover, agents that stimulate the release of cAMP also crossactivate the NO/cGMP cascade.
• Clinical Use: Prostaglandin E1 (PGE1; Alprostadil) is approved for the intracavernosal (Caverject, Edex)or intraurethral suppository (Muse) treatment of ED. A three-drug combination of PGE1, papaverine, and phentolamine sometimes is used as an intracavernosal injection to achieve a synergistic action. Erectile dysfunction that is medication-induced or caused by endocrine problems, such as hypogonadism or hyper- or hypothyroidism, should be evaluated and appropriately treated before PGE1 treatment is considered.

Technology Process of Alprostadil

There total 61 articles about Alprostadil which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 90.0%

C32H64O5Si2 (1251949-12-8) → ALPROSTADIL (745-65-3)

Guidance literature:

With hydrogen fluoride; water; In acetonitrile; at 20 ℃; for 6h; stereoselective reaction;

DOI:10.1016/j.tet.2010.07.069

Reference yield: 89.0%

prostaglandin E1 methyl ester (3434-33-1) → ALPROSTADIL (745-65-3)

Guidance literature:

With porcine pancreatic lipase; sodium chloride; calcium chloride; In tetrahydrofuran; water; for 0.5h; Enzymatic reaction; pH 7.1;

DOI:10.1002/(SICI)1099-0690(199910)1999:10<2655::AID-EJOC2655>3.0.CO;2-2

Reference yield:

furan (110-00-9) + 2-lithiofuran (2786-02-9) + stannane (7440-31-5) + ammonium chloride → ALPROSTADIL (745-65-3)

Guidance literature:

With ammonium hydroxide; n-butyllithium; pyridinium p-toluenesulfonate; In tetrahydrofuran; water; acetone;

upstream raw materials:

prostaglandin E₁ methyl ester

7-{(1R,2R,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-[(E)-(S)-3-(tert-butyl-dimethyl-silanyloxy)-oct-1-enyl]-5-oxo-cyclopentyl}-heptanoic acid

(8R,11R,12R,15S)-11,15-Bis-(2-trimethylsilylethoxymethoxy)-9-oxo-prost-13-en-1-oic acid 2-trimethylsilylethoxymethyl ester

(S)-E-3-(2-trimethylsilylethoxymethoxy)-1-tributylstannyl-1-octene

Downstream raw materials:

ethyl 7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoate

prostaglandin E₁ methyl ester

(11α,13E,15S)-11,15-dihydroxy-9-oxoprost-13-en-1-oic acid 4-(3H-1,2-dithiole-3-thione-5-yl)-phenyl ester

{1-[(4-methylphenyl)sulfonyl]-4-(nitrosothio)-4-piperidyl}methyl 7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R,4R,5R)-4-hydroxy-2-oxocyclopentyl]heptanoate

Refernces

• 1、 Sih,C.J. et al.. "". . p. 3643 - 3644. Retrieved 1972.
• 2、 Jung, Jae-Chul,Park, Oee-Sook. "Efficient asymmetric synthesis of prostaglandin E1". . p. 556 - 560. Retrieved 2007.
• 3、 -. "LOW-MOLECULE DRUG-CONTAINING NANOPARTICLE HAVING SUSTAINED RELEASE NEGATIVELY CHARGED GROUP". . . Retrieved 2010/03/31.