Naphthalene acetic acid analogues

The reeent intensive quest for non-steroid anti-inflammatory drugs and arylacetic acids in particular offer a brighter seope that the naphthalene acetic acid analogues might turn out to be the leading compounds of an extensive series of promising clinical agents. Example Naproxen. 

2-Acetyl-6-methoxy-naphthalene may be prepared by the acylation of 6-methoxynaphthalene. The resulting product is then subjected to a series of reactions, namely Wilgerodt-Kindler reaction, esterification, alkylation and hydrolysis ultimately yields /)Z-Naproxen. Resolution of the resulting racemic mixture is caused through precipitation of the more potent /)-enantiomer as the cinchonidine salt. 

It possesses analgesie, anti-inflammatory and anti-pyretic actions. It is normally used in the treatment of rheumatic or musculoskeletal disorders, rheumatoid arthritis, dysmenorrhea, and acute gout However, the sodium salt is mostly employed as an analgesic for a variety of other painful conditions. 

Dose Adult, in rheumatoid arthritis, 250 to 375mg as initial dose 2 times per day in acute gout, 750mg as loading dose followed by 250mg 3 times a day until relieved. 

It is a naphthalene acetic acid structural analogue available commercially as the acid and its sodium salt and is sold OTC. The drug is fairly comparable to aspirin both in the management and control of disease symptoms. Nevertheless, it has relatively lesser frequency and severity of nervous system together with milder GI-effects. 

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Heteroarylacetie aeid analogues 2. Arylacetic acid analogues 3. Arylpropionie aeid analogues 4. Naphthalene acetic acid analogues... 

Naproxen derived from naphthalene acetic acid analogue proved to be the leading compoimd of an extensive series of promising elinieal agents. Deseribe its synthesis from 6-methoxy naphthalene. 

Of the bicyclic acids, i-naphthaleneacetic acid (NAA, IX) is the best known structural analogue of indoleacetic acid, also resembling the natural auxin in many aspects of its actions. The fact that the isomeric 2-naphthalene-acetic acid (X) is very weakly active only, forms one of the most intriguing questions on structure-activity relationships, especially when compared with the inverse relations found with the naphthoxyacetic acids (c/. Section 4). 

A series of 2-(5-((naphthalen-6-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid analogues have been prepared as aldose reductase inhibitors. In vitro inhibitory activities of bovine lens aldose reductase were determined by a conventional method (Scheme 9.7). 

Metacyclophane (4a) behaves similarly on treatment with TFA, 4a and its derivatives 4b-d (s. Scheme 9) gave the corresponding benzocycloheptenes 24a-d (Structures 12) [66], Monohalogenated products 24e-f (Structures 12) were also obtained in the case of 4b-d, which were formed by abstraction of a halonium ion from cationic intermediates. Similar isomerization of the naphthalene analogue 64 (s. Scheme 16) was effected by acetic acid, giving orthocyc-lophane 89 (Structures 14) [43],... 

The analogues (24) of tropic acid have been made from the pentose dialdehyde derivative using the Grlgnard reagent derived from naphthalene acetic acld.- ... 

The initial stimulus for synthesizing analogues came mainly from the work of Zimmerman, Wilcoxon and Hitchcock - cf. also Haagen-Smit and Went ), which showed that naphthalene-i-acetic acid (II) and 2,4-dichlorophenoxyacetic acid (2,4-D, III) in several tests come up to the level of activity of lAA, while the practical implications of the selective toxicity of 2,4-D were discerned. 

An ingenious synthesis of steroidal annulenes has appeared. The close relationship of annulenes to the classical aromatic substance naphthalene stimulated the synthesis of l,6-methano-[10]annuleno-steroids, which are analogues of equilenin (97). The y,5-cyclopropyl-a -unsaturated ketone (98) was the initial target. Treatment of the cyclopropyl ketone (98) with acetic anhydride and methyl orthoformate in the presence of an acid catalyst then gave (99). Conversion of the cycloheptatriene (99) into the requisite 10 c-electron system (100) was then accomplished by dehydrogenation. ... 

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