Analgetics

Modifications of the morphine skeleton have produced butorphanol [42408-82-2] (35) and drotebanol [3176-03-2] (36), which in animal models have demonstrated antitussive activity much greater than that of codeine (51,52). Butorphanol is also a potent analgetic of the narcotic antagonist type (51). Both compounds possess a unique 14-hydroxyl group. 

Levopropoxyphene [2338-37-6] (42), the optical antipode of the dextrorotatory analgetic propoxyphene, is an antitussive without analgetic activity. The 2-naphthalenesulfonate salt has a less unpleasant taste than the hydrochloride salt, and is widely used. Clinical effectiveness has been demonstrated against pathological and artificially induced cough, but the potency is somewhat less than codeine. The compound is reported not to cause addiction. Levopropoxyphene can be prepared (62) by first resolving [ -dimethylamino-CX-methylpropiophenone with dibenzoyl-(+)-tartaric acid. The resolved... 

Tire tautomeric equilibrium of azocinones 65 has been studied by NMR, IR, and UV spectroscopy (90JHC1323). Dioxo derivatives of diazocines all exist as such, as illustrated by the analgetic 66 (75MI37) and the extensively studied dibenzo[h,/][l,4]diazocines (67) [81JCS(P1)988]. 

This drug is quite frequently found in headache remedies in com-liination with aspirin and caffeine (APC , PAG ). Although the iniline derivatives show analgetic potency comparable to aspirin,... 

Analgetic (analgesic). An agent that cau-ses the loss of response to pain without affecting the general level of consciousness. 

Fluproquazone (97) contains a 2-quinazolinone nucleus and is found to be an analgetic agent useful in mild to moderate pain. One of the preparations involves reaetion of 2-isopropylamino-4-methyl-4 -fluoro-benzophenone (96) with potassium cyanate in hot acetic acid [27],... 

Reaction of 2,6-dimethylaniline with thiophosgene produces isothiocyanate 171. When the latter is treated with 3-aminopropanol, thiourea 172 is formed, and this, when treated with hot concentrated hydrochloric acid, cyclizes to xylazine (173), an analgetic... 

Finally, three additional pyridazine-derived analgetic agents, which are cited in reference book [96] should be mentioned their structures are given in formulae (24), (25) and (26). 

A nonulcerogenic analgetic, antipyretric and nonsteroidal anti-inflammatory drug, glafenine was introduced in 1965 and was marketed under the brand names... 

Salicylic acid is manufactured on a large scale. In the dye industry it serves for the production of valuable azo-dyes which exhibit great fastness. To some extent these dyes are applied to mordanted fibres. In addition, the acid and its derivatives are widely used in pharmacy. Being a phenolcarboxylic acid it has a powerful disinfecting action (preservative). It has further proved itself an important antirheumatic and an analgetic. The derivative in which the phenolic hydroxyl group is acetylated (aspirin) has become especially popular. The first medicament of the series was the phenyl ester of salicylic acid, salol, which is produced as a by-product in the technical process. The preparation of salicylaldehyde has been described above (p. 235). 

Leonard, F., and I. Ehrenthal Thienyl-Substituted Aminoesters with Analgetic and Spasmolytic Properties. J. Amer. chem. Soc. 73, 2216 (1951). 

Badio B, Daly JW (1994) Epibatidine, a potent analgetic and nicotinic agonist. Mol Pharmacol 45 563-569... 

Aldrich, J.V., Virgil-Cruz, S.C. Narcotic analgetics, in Burger s Medicinal Chemistry and Drug Discovery, vol. vi Nervous System Agents, ed. Abraham, D. J., John Wiley Sons, New York, 2003, pp 329-481. 

Endorphins, dynorphins, and enkephalins are a particularly interesting group of neuropeptides. They act as endogenous opiates by producing analgetic, sedative, and euphoriant effects in extreme situations. Drugs such as morphine and heroin activate the receptors for these peptides (see p. 354). 

Aminonitrile formation on 125 with potassium cyanide and piperidine hydrochloride affords the derivative, 135. Hydrolysis as above gives the corresponding amide (136). Debenzylation is accomplished by catalytic reduction. Alkylation of the secondary amine with the side chain (96) used in the preparation of diphenoxylate affords pirintramide (138) This confound, interestingly enough, is an analgetic agent, although still one that follows the morphine rule, albeit in the side chain. 

Flick, K., Frankus, E Friderichs, E. Studies on chemical structure and analgetic activity of phenyl substituted aminomethylcyclohexanoles, Arzneim.-Forsch./Drug Res. 1978, 28 (I), 107-113. 

Synthesis (Pohland, 1953 1955 1963 janssen and Karel (Janssen)1956 Sullivan et al., 1963) In the Grignard reaction of 3-dimethylamino-2-methyl-1-phenyl-propan-lone with benzylmagnesium chloride 4-dimethylamino-3-methyl-1,2-diphenyl-butan-2-ol is formed. The preferred product is the a-diastereomer(75 % a-form, 15 % p-form). The a-form crystallizes and the diastereomeric p-form remains in solution, because of its better solubility. Racemic resolution to obtain the analgetically (+) enantiomer can be achieved on the pure a-Grignard product via fractional crystallization of the salts with D-camphorsulfonic acid. Alternatively the resolution can be achieved by treating the racemic mannich product 3-dimethylamino-2-methyl-1-phenyl-propan-1-one with (-)-dibenzoyltartaric acid in acetone as solvent. 

Friderichs, E., Felgenhauer, F., Jongschaap, P., Osterloh, G. [Pharmacological studies on analgesia, dependence on and tolerance of tramadol, a potent analgetic drug (author s transl)], Arzneimittelforschung 1978, 28, 122-134. 

Pert, C.B. and Snyder, S.H. Correlation of opiate receptor affinity with analgetic effects of meperidine homologues, J. Med. Chem. 1976, 19, 1248-1250. 

Dehmlow, E. V. Epibatidine competition synthetic work on a novel natural analgetic., J. Prakt. Chem. 1995, 337, 164-174. 

In conjunction with other bicyclic amidines, the indolamine N-methyl transferase inhibitory activities of 3,4,6,7,8,9-hexahydro-2//-pyrido[ 1,2-a]-pyrimidines have been studied.246 The analgetic and antiinflammatory activities of 6-oxopy rido [1,2-a] pyrimidines have been tested in comparison with those of phenylbutazone.221,222... 

Knoll, Meszaros and others studied the structure-activity relationship of analgetic 4-oxo-4W-pyrido[l,2-u]pyrimidine-3-carboxylic acid deriva-tives.133,258 389,390 Following detailed investigations,391-436 derivatives... 

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