Phentolamine

Base Information

• Chemical Name: Phentolamine
• CAS No.: 50-60-2
• Molecular Formula: C17H19N3O
• Molecular Weight: 281.357
• Hs Code.: 2933290090
• European Community (EC) Number: 200-053-1
• UNII: Z468598HBV
• DSSTox Substance ID: DTXSID4023462
• Nikkaji Number: J4.105J
• Wikipedia: Phentolamine
• Wikidata: Q420360
• NCI Thesaurus Code: C62066
• RXCUI: 8153
• Pharos Ligand ID: 1AMCCN88WLZC
• Metabolomics Workbench ID: 43005
• ChEMBL ID: CHEMBL597
• Mol file: 50-60-2.mol

Synonyms:Fentolamin;Mesilate, Phentolamine;Mesylate, Phentolamine;Methanesulfonate, Phentolamine;Mono-hydrochloride, Phentolamine;Phentolamine;Phentolamine Mesilate;Phentolamine Mesylate;Phentolamine Methanesulfonate;Phentolamine Mono hydrochloride;Phentolamine Mono-hydrochloride;Regitine;Regityn;Rogitine;Z-Max

Chemical Property of Phentolamine

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 1.16E-10mmHg at 25°C
• Melting Point: 177 - 178oC
• Refractive Index: 1.625
• Boiling Point: 550.984 °C at 760 mmHg
• PKA: pKa 7.7 (Uncertain)
• Flash Point: 287.025 °C
• PSA: 47.86000
• Density: 1.185 g/cm³
• LogP: 2.60480
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 281.152812238
• Heavy Atom Count: 21
• Complexity: 363

Purity/Quality:

99% ^*data from raw suppliers

PHENTOLAMINE 95.00% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC=C(C=C1)N(CC2=NCCN2)C3=CC(=CC=C3)O
• Recent ClinicalTrials: Role of Sympathetic Vasoconstriction on Insulin-Mediated Microvascular Recruitment and Glucose Uptake in Obesity
• Recent EU Clinical Trials: Phentolamines and their role in everyday dentistry
• Recent NIPH Clinical Trials: Magnesium sulfate versus combination of magnesium and phentolamine for control of blood pressure in pregnancy induced hypertension
• description: Phentolamine is an α-adrenergicreceptor antagonist approved for use by the U.S.Food and Drug Administration (FDA) in 1952. Approved uses of phentolamine currently include (1) diagnosis of pheochromocytoma,(2) treatment of hypertension in pheochromocytoma, and (3) prevention of tissue necrosis after norepinephrine extravasation. Anearly use of injectable phentolamine involved the management of impotence (erectile dysfunction). Phentolamine is a short-acting, competitive antagonist at peripheral o-adrenergic receptors. It antagonizes both a and ozreceptors,thus blocking the actions of the circulating catecholamines epinephrine and norepinephrine. Phentolamine also stimulates β-adrenergic receptors in the heart and lungs.
• Uses: Phentolamine is a synthetic imidazoline with alpha-adrenergic antagonist activity. As a competitive alpha-adrenergic antagonist, phentolamine binds to alpha-1 and alpha-2 receptors, resulting in a decrease in peripheral vascular resistance and vasodilatation. This agent also may block 5-hydroxytryptamine (5-HT) receptors and stimulate release of histamine from mast cells. Phentolamine is used mainly in the diagnosis of pheochromocytoma and to control or prevent paroxysmal hypertension immediately prior to or during pheochromocytomectomy. Phentolamine has been used to treat hypertensive crises secondary to MAO inhibitor/sympathomimetic amine interactions and rebound hypertension on withdrawal of clonidine, propranolol or other antihypertensive agents. Phentolamine is used for peripheral blood circulation disorders, in particular in the beginning stages of gangrene, for treatment of trophic ulcers of the extremities, bedsores, and frostbite. Anti-adrenergic. Phentolamine is used to prevent or control hypertensive episodes that occurin patients with pheochromocytoma. It also has been used incombination with papaverine to treat impotence.
• clinical use: The clinical effects of phentolamine include peripheral vasodilation and tachycardia.Vasodilation results from both direct relaxation of vascular smooth muscle and a blockade. The drug produces positive inotropic and chronotropic effects,leading to an increase in cardiac output.In smaller doses, the positive inotropic effect can predominate and raise blood pressure; in larger doses, peripheral vasodilation can mask the inotropic effect and lower blood pressure.These actions make phentolamine useful in treating hypertension caused by increased circulating levels of epinephrine and norepinephrine, as occurs in pheochromocytoma. The effects of phentolamine in treating impotence are mediated by α-adrenergic blockade in penile blood vessels. Actions of the drug cause relaxation of the trabecular cavernous smooth muscles and dilation of the penile arteries; this increases arterial blood flow into the corpus cavernosa and subsequently causes an erection. Phentolamine is administered IV or IM but can be injected subcutaneously to prevent local tissue necrosis when vasoconstrictor drugs extravasate. The pharmacokinetics of phentolamine is largely unknown;10% of a parenteral dose is excreted in the urine unchanged.
• Description: Phentolamine is also a derivative of imidazoline that exhibits a direct α-adrenoblocking, muscle-relaxant effect on smooth muscle as well as cholinomimetic, histamine, and sympathomimetic effects. The chemical variation of its structure permits a few of its properties to be more expressed. For example, the aforementioned tolazoline, 2-benzyl-2-imidazoline, a structural analog of phentolamine, has more of an expressed muscle-relaxant effect on smooth muscle than an α-adrenoblocking effect.
• Indications: Human erectile tissue has a population of membrane receptors that are predominantly of the -adrenoceptor subtype. Phentolamine (Vasomax) is a nonselective - adrenoceptor blocking agent (see Chapter 11), and like other such agents, it has been used to treat ED. Nonselective adrenoceptor antagonists may provoke a reflex that increases both sympathetic outflow and the release of norepinephrine.
• Therapeutic Function: Adrenergic blocker
• Clinical Use: Phentolamine has been used orally and intracavernosally in the treatment of ED. Following oral administration, phentolamine has a plasma half-life of about 30 minutes and a duration of action of 2 to 4 hours. An intracavernosal injection of phentolamine results in the drug reaching maximum serum levels in about 20 to 30 minutes. It is rapidly metabolized. Phentolamine has been used in combination with papaverine, chlorpromazine, and vasoactive peptides in the treatment of ED.

Technology Process of Phentolamine

There total 6 articles about Phentolamine 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: 49.0%

4-methyl-3'-hydroxydiphenylamine (61537-49-3) + 2-(chloromethyl)-2-imidazoline hydrochloride (13338-49-3) → phentolamine (50-60-2)

Guidance literature:

With triethyl phosphite; In toluene; for 6h; Heating;

DOI:10.1021/acs.orglett.8b00473

Reference yield:

1-methylcyclohexan-4-one (589-92-4) → phentolamine (50-60-2)

Guidance literature:

Multi-step reaction with 2 steps

1: styrene; 10 wt% Pd(OH)2 on carbon / toluene / 24 h / 140 °C / 3750.38 Torr / Flow reactor

2: toluene / Reflux

With styrene; 10 wt% Pd(OH)2 on carbon; In toluene;

DOI:10.1002/anie.202005109

Reference yield:

p-cresol (106-44-5) → phentolamine (50-60-2)

Guidance literature:

Multi-step reaction with 3 steps

1: hydrogen; palladium on activated charcoal / toluene / 140 °C / 1500.15 Torr / Flow reactor

2: styrene; 10 wt% Pd(OH)2 on carbon / toluene / 24 h / 140 °C / 3750.38 Torr / Flow reactor

3: toluene / Reflux

With styrene; palladium on activated charcoal; 10 wt% Pd(OH)2 on carbon; hydrogen; In toluene;

DOI:10.1002/anie.202005109

upstream raw materials:

4-methyl-3'-hydroxydiphenylamine

2-(chloromethyl)-2-imidazoline hydrochloride

ethylenediamine

meta-nitrophenol

Downstream raw materials:

phentolamine mesylate

Refernces

• 1、 Roscales, Silvia,Csák?, Aurelio G.. "Synthesis of Di(hetero)arylamines from Nitrosoarenes and Boronic Acids: A General, Mild, and Transition-Metal-Free Coupling". supporting information. p. 1667 - 1671. Retrieved 2018/03/23.