58-74-2 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.
Check Digit Verification of cas no
The CAS Registry Mumber 58-74-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 8 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 58-74:
(4*5)+(3*8)+(2*7)+(1*4)=62
62 % 10 = 2
So 58-74-2 is a valid CAS Registry Number.
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
58-74-2Relevant articles and documents
Photochemistry and photophysics of papaverine N-oxide
Souto-Bachiller,Perez-Inestrosa,Suau,Rico-Gomez,Rodriguez-Rodriguez,Coronado-Perez
, p. 875 - 881 (1999)
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.
KLEINSCHMIDT,MOTHES
, p. 52 - 56 (1959)
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Easy access to drug building-blocks through benzylic C-H functionalization of phenolic ethers by photoredox catalysis
Brandhofer, Tobias,Derdau, Volker,García Manche?o, Olga,Méndez, María,P?verlein, Christoph,Stinglhamer, Martin
supporting information, p. 6756 - 6759 (2021/07/13)
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
Opsomer, Tomas,Van Hoof, Max,D'Angelo, Andrea,Dehaen, Wim
supporting information, p. 3596 - 3600 (2020/04/21)
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.