58-74-2

Basic information

• Product Name: PAPAVERINE HYDROCHLORIDE
• Synonyms: Papaverine,99%;18) META CHLORO BENZALDEHYDE;isoquinoline, 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethox;Papacon;Papalease;Papanerin-HCl [German];Papaveri;PAPAVERINE
• CAS NO: 58-74-2
• Molecular Formula: C₂₀H₂₁NO₄
• Molecular Weight: 375.85
• EINECS: 200-502-1
• Mol File: 58-74-2.mol
• Article Data: 36

Chemical Properties

• Melting Point: 226 °C
• Boiling Point: 475.36°C (rough estimate)
• Flash Point: 172.2°C
• Appearance: white/powder
• Density: d420 1.337
• Refractive Index: 1.6250 (estimate)
• Solubility: H2O: 25 mg/mL
• PKA: 6.4(at 25℃)
• Water Solubility: 37.33mg/L(37.5 oC)
• Merck: 14,7019
• BRN: 312930
• CAS DataBase Reference: PAPAVERINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: PAPAVERINE HYDROCHLORIDE(58-74-2)
• EPA Substance Registry System: PAPAVERINE HYDROCHLORIDE(58-74-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 22
• RIDADR: UN 1544 6.1/PG 3
• WGK Germany: 1
• RTECS: NW8575000
• F: 8
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 58-74-2(Hazardous Substances Data)

Usage

Chemical Properties

White crystalline powder; obtained asorthorhombic prisms from an alcohol–ethermixture; melts at 147°C (296.6°F); sublimesunder vacuum; insoluble in water; soluble inacetone, glacial acetic acid, and benzene.

Originator

Lempav Ty-Med ,Lemmon,US,1975

Uses

Different sources of media describe the Uses of 58-74-2 differently. You can refer to the following data:
1. Papaverine occurs in opium to the extent of0.8–1.0%, commonly associated with narcotine.It is used as a smooth muscle relaxantand in medicine for its vasodilator action onthe blood vessels in the brain. It is effectiveagainst asthma.
2. folate metabolic inhibitor, coccidiostat
3. opium alkaloid

Definition

ChEBI: A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.

Indications

Papaverine (Pavabid) is a nonspecific phosphodiesterase inhibitor that increases cAMP and cGMP levels in penile erectile tissue. Papaverine is particularly known as a smooth muscle relaxant and vasodilator. Its principal pharmacological action is as a nonspecific vasodilator of smooth muscles of the arterioles and capillaries. Various vascular beds and smooth muscle respond differently to papaverine administration both in intensity and duration. Papaverine decreases the resistance to arterial inflow and increases the resistance to venous outflow.

Manufacturing Process

To 3.65 g (0.01 mol) of monohydrated adenosine-5'-monophosphoric acid, brought into suspension in a mixture of 45 ml of water and 5 ml of ethanol, are added 339 g (0.01 mol) of papaverine base (melting point, 147°C). The mixture is gently heated until a final temperature of 40°C is reached. The solution obtained is then filtered and the filtrate is concentrated under vacuum. The remaining product quickly crystallizes. After drying to 50°C to constant weight, there are obtained 6.68 g of desired product, in the monohydrated state, as a white crystalline powder, which melts at 140°C and is very soluble in water.

Brand name

Pavabid (Hoechst Marion Roussel).

Therapeutic Function

Vasodilator, Platelet aggregation inhibitor

Health Hazard

Papaverine is an inhibitor of cyclic nucleotidephosphodiesterase, producing vasodilatoryeffect. The acute toxic effects relative tophenanthrene-type opium alkaloids (e.g.,morphine, heroin) are low and the symptomsare not the same. Papaverine is neither a narcoticnor an addictive substance. Excessivedoses may produce drowsiness, headache,facial flushing, constipation, nausea, vomiting,and liver toxicity.The LD50 data reported in the literatureshow variation. An oral LD50 value in rats ison the order of 400 mg/kg.

Mechanism of action

When administered by intracavernosal injection, papaverine, a weak and nonspecific PDE inhibitor, is thought to cause relaxation of the cavernous smooth muscles and vasodilation of the penile arteries by inhibition of PDE. These effects result in increased arterial blood flow into the corpus cavernosa and in swelling and elongation of the penis. Venous outflow also is reduced, possibly as a result of increased venous resistance.

Clinical Use

Papaverine is highly effective in men with psychogenic and neurogenic ED but less effective in men with vasculogenic ED. Papaverine–phentolamine combinations have been used in self-injection procedures. Papaverine doses may range from 15 to 60 mg. Papaverine treatment in patients with severe arterial or venous incompetence is usually unsuccessful, but autoinjections using low doses sufficient to achieve an erection are safe and efficient.

Side effects

Major side effects associated with papaverine therapy include priapism, corporeal fibrosis, and occasional increases in serum aminotransferases. Intracorporeal scarring may be related to the low pH of the vehicle that is necessary to solubilize papaverine.Attempts to buffer papaverine to render it more suitable for intracavernosal injection have not been entirely satisfactory, and such delivery may still lead to intracorporeal scarring.

Safety Profile

Poison by ingestion, intramuscular, subcutaneous, intradermal, intraperitoneal, and intravenous routes. Human systemic effects: coma, somnolence. Its central nervous system action is about midway between those of morphme and codeine, and large doses do not produce the amount of excitement caused by codeine or the soporific action of morphine. Mutation data reported. A cerebral vasodilator and smooth muscle relaxant. Combustible when exposed to heat or flame. When heated to decomposition it emits toxic fumes of NOx. See also MORPHINE.

Synthesis

Papaverine, 1-veratryl-6,7-dimethoxyisoquinolin (19.4.7), is synthesized from veratrol. Veratrol undergoes chloromethylation, forming 3,4-dimethoxybenzylchloride (19.4.1). Reacting this with potassium cyanide gives 3,4-dimethoxybenzylcyanide (19.4.2). The resulting 3,4-dimethoxybenzylcyanide undergoes reduction by hydrogen over Raney nickel, forming homoveratrylamine (19.4.3). At the same time 3,4-dimethoxybenzylcyanide (19.4.2) undergoes acidic hydrolysis giving 3,4-dimethoxyphenylacetic acid (19.4.4). The interaction of the resulting compounds brings to corresponding amide (19.4.5). The cyclization of this by Bischler–Napieralski method, using phosphorous oxychloride, gives 3,4-dihydropapaverine (19.4.6), which is dehydrated into the desired papverine when heated in tetraline at high temperatures.

InChI:InChI=1/C20H21NO4/c1-22-17-6-5-13(10-18(17)23-2)9-16-15-12-20(25-4)19(24-3)11-14(15)7-8-21-16/h5-8,10-12H,9H2,1-4H3

Upstream product

• 60-18-4 L-tyrosine 
• 73168-84-0 1-(2-iodo-4,5-dimethoxybenzyl)-6,7-dimethoxyisoquinoline 
• 51449-10-6 1-(2'-bromo-4',5'-dimethoxybenzyl)-6,7-dimethoxyisoquinoline 
• 33520-96-6 Bis[1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisochinolin-2-oxid] 
• 139-76-4 N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)acetamide 
• 61-25-6 papaverine hydrochloride 
• 5884-22-0 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3.4-dihydroisoquinoline hydrochloride 
• 140696-57-7 Benzoic acid (R)-((S)-2-benzoyl-6,7-dimethoxy-1,2-dihydro-isoquinolin-1-yl)-(3,4-dimethoxy-phenyl)-methyl ester 
• 2679-26-7 2-Methylpapaverinium iodide 
• 102449-80-9 6,7-dimethoxy-1-veratryl-3,4-dihydro-isoquinoline-3-carboxylic acid 
• 861056-23-7 (3,4-dimethoxy-phenyl)-acetic acid-(3,4,β-trimethoxy-phenethylamide) 
• 78004-24-7 (3,4-dimethoxy-phenyl)-acetic acid-(β-hydroxy-3,4-dimethoxy-phenethylamide) 
• 50299-95-1 2-benzoyl-1-cyano-6,7-dimethoxy-1,2-dihydroisoquinoline 
• 591-51-5 phenyllithium 

Downstream Products

• 577-68-4 m-hemipinic acid 
• 522-57-6 papaveraldine 
• 123348-80-1 3-hydroxy 6-demethyl papaveraldine 
• 115698-47-0 4-hydroxy 6-demethyl papaveraldine 
• 123348-81-2 3-hydroxy 4'-demethyl papaveraldine 
• 115698-48-1 4-hydroxy 4'-demethyl papaveraldine 
• 144-62-7 oxalic acid 
• 93-07-2 Veratric acid 
• 23740-74-1 papaveroline hydrobromide 
• 113542-03-3 6'-bromopapaveraldine 
• 113542-05-5 6'-bromopapaverine N-oxide 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 88205-34-9 2-acetamido-1-(3',4'-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 88205-36-1 1-(3',4'-dimethoxybenzyl)-6,7-dimethoxy-2-(N-methylacetamido)-1,2,3,4-tetrahydroisoquinoline 

Relevant articles and documents

Photochemistry and photophysics of papaverine N-oxide

The photochemistry and photophysics of papaverine N-oxide in polar aprotic and protic solvents has been studied in detail. Complex energy and charge-transfer phenomena between chromophores occur in papaverine. New photochemistry for the papaverine N-oxide system is reported. Irradiation in protic media results in the formation of an emissive charge-transfer state with ensuing intramolecular hydroxylation in high isolated yields (75-80%).

Physiology and biosynthesis of alkaloids of Papaver sominferum.

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Easy access to drug building-blocks through benzylic C-H functionalization of phenolic ethers by photoredox catalysis

A visible light-mediated photocatalyzed C-C-bond forming method for the benzylic C-H functionalization of phenolether containing synthetic building blocks based on a radical-cation/deprotonation strategy is reported. This method allows the mild, selective generation of benzyl radicals in phenolic complex molecules and drug-like compounds, providing new entries in synthetic and medicinal chemistry.

1,2,3-Triazole-Mediated Synthesis of 1-Methyleneisoquinolines: A Three-Step Synthesis of Papaverine and Analogues

A metal-free three-step synthesis toward functionalized 1-methyleneisoquinolines from readily available substrates is reported. First, acetal-containing 1,2,3-triazoles were prepared via a high-yielding triazolization reaction and quantitatively converted into triazolo[5,1-a]isoquinolines. Next, the acid-promoted ring opening of these fused triazoles was studied in order to obtain coupling to a diverse scope of nucleophiles, including carbon nucleophiles such as veratrole. By means of non-nucleophilic strong acids under anhydrous conditions, a series of unprecedented isoquinolines and imidazo[5,1-a]isoquinolines was synthesized.