Papaverine structure

CgHjoO,. A compound of largely historical interest for its role in establishing the structure of many natural products. Methylation of vanillin gives veratraldehyde which may be oxidized to veratric acid. Veratric acid was identified as a degradation product of the alkaloid papaverine. 

In this, the first serious and successful work on the structure of a complex alkaloid, there was naturally at first some confusion between Moquinoline and the better-known quinoline. The 6 7-dimethoxy-woquinolinecarboxylic acid was thought to be a dimethoxycinchoninic acid. It known, however, that quinoline benzylchloride on oxidation furnished formylbenzylanthranilic acid, CjH4(COOH)—N(C,H,)—CHO, whereas various papaverine alkyl halides gave what were presumed to be... 

As shown in Scheme 26, Papaverine hydrochloride yields a separable mixture of Protopapaverine (67) and the salt norpapaverinium chloride (68) when heated slightly beyond its melting point for several minutes. Molecule 67 can exist as conjugated mesomeric betaine 67A (7-hydroxy form) or as 2-substituted-2//-isoquinolin-6-one 67B (6-hydroxy form) (66TL1177). Similar structures were described as zwitterionic pentacyclic... 

Although this isoquinoline at first bears little structural resemblance to morphine (108), careful rearrangement of the structure (A) shows the narcotic to possess the benzylisoquinoline fragment within its framework. Indeed, research on the biogenesis of morphine has shown that the molecule is formed by oxidative coupling of a phenol closely related to papaverine. 

FIG. 22 Chemical structures of (a) dextromethorphan hydrobromide, (b) papaverine hydrochloride, (c) quinine hydrochloride, and (d) berberine chloride. 

Diarylalkanes are important structural motifs that can be found in a variety of pharmaceuticals, agrochemicals and fine chemicals. Examples are papaverin, avrainvilleol and beclobrate (Scheme 2). Traditionally, 1,1-diarylalkanes can be prepared from benzyl halides and the corresponding arenes under Friedel-Crafts-type conditions. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent. 

Verapamil, the first clinically useful member of this group, was the result of attempts to synthesize more active analogs of papaverine, a vasodilator alkaloid found in the opium poppy. Since then, dozens of agents of varying structure have been found to have the same... 

Papaverine (Figure 6.45) is a benzylisoquinoline alkaloid, and is structurally very different from the morphine, codeine, thebaine group of alkaloids (morphinans). It has little or no analgesic or hypnotic properties put possesses spasmolytic and vasodilator activity. It has been used in some expectorant preparations, and in the treatment of gastrointestinal spasms, but its efficacy was not substantiated. It is sometimes used as an effective treatment for male impotence, being administered by direct injection to achieve erection of the penis. 

Hanna and Shutt (146) studied the relationship between the chemical structure and the coronary dilator action of papaverine analogs on anesthetized dogs. The 6-alkoxy-, 5,6-dialkoxy-, and 6,7-dialkoxy-isoquinoline derivatives acted as dilators. The 6,7-dialkoxyisoquinoline derivatives were most effective. Optimum results were obtained when the isoquinoline nucleus was aromatic, but the 3,4-dihydro- and 1,2,3,4-... 

In rats, papaverine had a choleretic effect (271). It caused relaxation of the duodenum, of the sphincter of Oddi, and of the muscles of the bile duct (272-277). It paralyzed the spasmogenic effect of morphine on these structures. Papaverine (0.36 g) in combination with 100 ml of 60% sorbitol, administered to man by means of a duodenal probe, showed a higher choleretic and a lower cholecystokinetic effect than a 30% solution of magnesium sulfate (277). 

Therapeutic Function Vasodilator, Platelet aggregation inhibitor Chemical Name Papaverine adenosine 5-monophosphate Common Name Papaverine adenylate Structural Formula ... 

Completely unrelated structures have appeared in the patent literature disclosed by Japanese inventors (Figure 9.33). The two imidazole derivatives 139 and 140 are micromolar PDE1 inhibitors [114]. More potent, and bearing some structural resemblance to the alkaloid papaverine, are the quinazolines 141 and 142 from... 

In 1803 the German pharmacist Seturner achieved the isolation of morphine as one of the active ingredients of opium. He named the compound after Morpheus, Ovid s god of dreams, the son of sleep. Among the other alkaloids of opium are codeine, isolated in 1832, thebaine, narceine, narcotine, and papaverine. From the isolation of pure morphine to the elucidation of its structure by first Gulland and Robinson(1,2) and later Schopf(3) took another 120 years. A total synthesis by Gates and Tschudi(4,5) confirmed the structure in the early 1950s. 

Papaverine is an alkaloid present in opium, but is structurally unrelated to morphine. It inhibits phosphodiesterase and its principal action is to relax smooth muscle throughout the body, especially in the vascular system. It is occasionally injected into an area where local vasodilatation is desired. 

Verapamil is a synthetic compound possessing slight structural similarity to papaverine. It can be separated into its optically active isomers, of which the levorotatory enantiomer is the most potent. It is absorbed rapidly after oral administration. The drug is metaboli zed quickly and. as a result, has low bioavailability. The liver is the main site of first-pass metaboli.sm. forming several products. The preferential metabolic step involves N-dealkylation. followed by O-demethylation. and subsequent conjugation of the product before elimination. The metabolites have no significant biological activity. Verapamil has an elimination half-life of approximately 5 hours. 

Two basic types of structures arc recognized among the opium alkaloids, the plmnanthreite (morphine) type and the benzylisoqtiinoline (papaverine) type (.see structures). 

In 1886 Guido Goldschmiedt reduced papaverine with tin and hydrochloric acid and isolated 1,2,3.4-tetrahydropapaverine and a crystalline base now known as pavine, the structure of which was established by Battersby and Binks. ... 

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