2- Methyl-5-methoxy-3-indole acetic acid

The indomethacin hydrolysis product 2-methyl-5-methoxy indole acetic acid fluoresces at 385 nm after excitation at 300 nm in 0.1N NaOH,(41) and at 387 nm after excitation at 312 nm in pH 11.6 buffer(42). The latter procedure claimed a threefold increase in detectability. Neither method distinguishes indomethacin from salicylates. Clinical studies employing subjects administered aspirin must use a separation prior to fluorescence analysis. Without adequate separation the indole metabolites as well as salicylate, produce a positive assay bias. 

Indomethacin and Analogs - Among several isosteric modifications of indomethacin studied at Merck, an indene isoster, cis -1-p-chloro-benzylidenyl-5-methoxy-2-methyl-3-indenylacetic acid (VII), was found to be half as active as indomethacin. The corresponding "trans isomer was only one-tenth as active. The structure-activity relationship of Nj-aroyl and N.-aralkyl indole acetic acids is generally parallel to that of indene isosters, indicative of a similar mode of action. Based on X-ray diffraction data, the nonplanar configuraticn of the cis-isomer was suggested as the preferred conformation of... 

Coned. H2SO4 added to a soln. of 2-phenyl-3-carbethoxy-5-methoxy 6-methyl-benzofuran in acetic acid, and refluxed 1 hr. -> 2-phenyl-5-methoxy-6-methyl-benzofuran. Y 91.5%. F. e., also indole derivatives, and use of coned. H3PO4 instead of H2SO4, s. A. N. Grinev et al., X. 28, 1853 (1958) C. A. 53, 1299a. 

CN I -(4-chlorobenzoyl)-5-methoxy-2-methyl-1 //-indole-3-acetic acid carboxymethyl ester... 

CN ( )-l-(4-chlorobenzoyl)-5-methoxy-2-methyl-lH-indole-3-acetic acid 2-I4-[3-[[4-(benzoylamino)-5-(dipropylamino)-1,5-dioxopentyl]oxy]propyl]-1 -piperazinyl]ethyl ester... 

Structural information on aromatic donor molecule binding was obtained initially by using H NMR relaxation measurements to give distances from the heme iron atom to protons of the bound molecule. For example, indole-3-propionic acid, a structural homologue of the plant hormone indole-3-acetic acid, was found to bind approximately 9-10 A from the heme iron atom and at a particular angle to the heme plane (234). The disadvantage of this method is that the orientation with respect to the polypeptide chain cannot be defined. Other donor molecules examined include 4-methylphenol (p-cresol) (235), 3-hydroxyphenol (resorcinol), 2-methoxy-4-methylphenol and benzhydroxamic acid (236), methyl 2-pyridyl sulfide and methylp-tolyl sulfide (237), and L-tyrosine and D-tyrosine (238). Distance constraints of between 8.4 and 12.0 A have been reported (235-238). Aromatic donor proton to heme iron distances of 6 A reported earlier for aminotriazole and 3-hydroxyphenol (resorcinol) are too short because of an inappropriate estimate of the molecular correlation time (239), a parameter required for the calculations. Distance information for a series of aromatic phenols and amines bound to Mn(III)-substituted HRP C has been published (240). 

Chloro-benzoyl)-5-methoxy-2-methyl-1 H-indol-3-yl]-acetic acid, C19H16CIN04, Mr 357.79, mp 153-154 °C (crystals exhibiting polymorphism, mp for another form is 162 °C) sodium trihydrate [ 74252-25-8], C19H15CINNa04. 3H20, Mr 433.82, pale yellow crystaline powder... 

Amino-4-methoxy-l-methoxymethylnaphthalene 120, obtained from the chloromethyl derivative 111, is transformed into azide 121. The latter undergoes photolytic heterocyclization to the labile 5-methoxyben-zo[cd]indole 117 which, on reduction by lithium aluminium hydride followed by acetylation, is converted into the stable l-acetyI-5-methoxy-l, 2-dihydrobenzo[o/]indole 119 (R = OMe) [71JCS(C)721]. The reduction of methyl or phenyl 8-nitro-1 -naphthyl ketones by hydrogen and platinum dioxide or by iron in acetic acid leads to a mixture of products (59M634). 

HI - 1H-INDOLE-3-ACETIC ACID, l-(4-CHLOROBENZOYL)-5-METHOXY-2-METHYL-CARBOXYMETHYL ESTER RN - 53164-05-9... 

H-INDOLE-3-ACETIC ACID, l-(1t-CHLOROBENZOYL)-5-METHOXY-2-METHYL-2-( t-(3-((It-(BENZOYLAMINO)-5"(DIPROPYLAMINO)-1,5-DIOXOPENTYL)OXY)PROPYL)-1 -PIPERAZINYL)ETHYL ESTER ( -)-, (Z)-2-BUTENEDI0ATE (1 2)... 

Chemical Name lH-Indole-3-acetic acid, 5-methoxy-2-methyl-l-(l-oxo-3-phenyl-2-propenyl)-... 

Chemical Name lH-Indole-l-acetic acid, 3-(4-chlorobenzoyl)-6-methoxy-2-methyl-... 

To a solution of the S-(+)-4-acethoxy-9-[2-(5-ethyl-l,2,3,6-tetrahydro-pyridin-3yl)-l-(lH-indol-2-yl)-l-methoxycarbonyl-ethyl]-3a-ethyl-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,ll,12,12b-octahydro-lH-6,12a-diaza-indeno[7,l-ca]fluorene-5-carboxylic acid methyl ester in dioxane and glacial acetic acid was added 37% aqueous formaldehyde and the mixture stirred at 35°C for 24 h. The solution was evaporated in vacuo and the residue suspended in chloroform and washed with cold aqueous 5% K2C03 solution. The chloroform layer was dried (MgS04), filtered, and evaporated. The residue was chromatographed eluting with EtOAc/MeOH, 10% NH4OH to give the product navelbine. 

In a study NSAIDs indomethacin (2-[l-(4-chlorobenzoyl)-5-methoxy-2-methyl-indol-3-yl]acetic acid), acemetacin (l-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid carboxymethyl ester), and etodolac (( )-l,8-diethyl-l,3,4,9-tetrahydropyrano-(3,4-b)indole-l-acetic acid) were tested on different ROS generating systems (Fig. 1). There are some satisfactory results that confirm that the anti-inflammatory activity of these compounds may be also partly due to their ability to scavenge ROS and RNS. The observed effective scavenging activity may contribute to the anti-inflammatory therapeutical effects [92,100]. 

In a systematic search for novel analogues of the anti-inflammatory indole-3-acetic acid derivative indomethacin (216), scientists at the Pierrel Laboratories in Milan reasoned that substitution of an azido group for the 4-chloro substituent on the A-benzoyl ring might represent an effective bioisosteric replacement, and thus confer interesting biological properties to the molecule [266]. l-(4-Azidobenzoyl)-5-methoxy-2-methyl-l/f-indole-3-acetic acid (zidometacin) (217) was synthesized and evaluated for its... 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

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