2- Indolones

The photolysis of 2,3,4-triphenylisoxazolin-5-imine generated an imidazolone and an indolone via an aziridinone <70LA(732)195,74CB13). Acid treatment of the imine transformed it into an indole (Scheme 70) <74CB13). 

The Af-oxide of indolone rearranged to produce 3-benzoyl-2,1-benzisoxazole (65JOC1104, and an isoxazolyl-2,1-benzisoxazole (587) was prepared from a benzilideneacetylacetone... 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

Significant progress has been made in the development of nonpeptidic ligands for the GAL3 receptor (Fig. 1). 3-Arylimino-2-indolones including SNAP 37889 and SNAP 398299 were shown by Swanson... 

Merour J. Y., Piroelle S., Joseph B. Synthesis and Reactivity of lH-Indol-3(2H)-One and Related Compounds Trends Heterocycl. Chem. 1997 J 115-126 Keywords inverse electron-demand Diels-Alder reaction, indolone... 

Indolones and isoindolones have been utilised in the synthesis of fused azepine derivatives. In the one reaction, rearrangement of the alkynes 18 to 2-benzazepine-l,5-diones 19 in the presence of Lewis acids has been reported <96XL393>. Xhe yields vary from moderate to very good. Xricyclic azepines 20 are obtained by the reaction of the 4-[2 -(p-toluenesulfonyloxy)ethyl]-2-oxindole with imines <96JHC209>. 

Incorporation of fluorine at a site adjacent to a "metabolic soft spot" has also been used as a strategy to increase duration of action. Linopir-dine (24) was among the first clinical compounds that enhanced potassium-evoked release of acetylcholine in preclinical models of AD [22]. Linopirdine showed no clinical efficacy and its human pharmacokinetic profile was suggested as the reason for this lack of clinical efficacy. Specifically noted was the molecule s poor brain exposure and short half-life due to formation of the N-oxides 25 and 26 (Table 3) [23,24]. Optimization of 24 resulted in replacement of the indolone core by the anthracenone 27, which had improved in vitro activity, but still exhibited a short duration of action. To improve the metabolic stability, fluorine... 

Ring expansion of 4J5>6,7-tetrahydro-4-indolone oximes also underpinned the synthesis of the 3//-azeto[l,2-a]pyrrolo[3,2-c]azepin-8-ones 30 (eg. R = H, Me) in good yield <00H(53)557>. 

In this process o-nitrobenzaldehyde is condensed in alkaline solution with acetone. The so-called o-nitrophenyUactic acid ketone thus formed loses acetic acid, and by further loss of a molecule of water is changed into indolone, which corresponds to half of the indigo molecule. Possibly o-nitrostyrene is an intermediate stage in this transformation. Indolone cannot exist in the free state, and hence polymerises at once to the dye ... 

An ingenious multi-step synthesis of oxo[l,3]thiazolo[5,4-/]azocine 214 is based on the transformations of ethyl tetrahydro[l,3]benzothiazolyl acetate 209 (81CPB1780 Scheme 59). Under the action of methylamine, 209 cyclizes to thiazolo[4,5-e]indolone 210 which, through compounds 211 and 212, converts into quaternary salt 213. The key stage of the process is the efficient rearrangement of this salt into thiazoloazocine under the action of alcoholic base. 

The base-catalyzed reaction of 4-hydroxycoumarin 184 with indolones 213 or with isatin and MN 27a on short heating leads to spiro pyrano-benzopyrans 220 (89JHC1097, 05RCB992, 08JCO741, 08RCB2373) (Scheme 82). 

Under analogous conditions, the 3-cyanomethylene-2-indolones 213 react with barbituric acid and its derivatives 191 with the formation of spiro-annulated pyranopyrimidines 223 (88JIC202, 90H(31)31)... 

N-Methyl-4-hydroxy-2-quinolone 183 in a three-component reaction gives spiro pyrano[3,2-c]qionoline-2-ones (02MI2), but indolones 213 with 4-hydroxy-6-methyl-2-pyridone 177 react in a complicated way (97BCJ1625). Ethoxycarbonyl-methylene indolone (Z = COOEt) forms pyrans 224, while dicyano analogs (Z = CN) yield substituted quinoline 225 (Scheme 85). 

N-Phenylpyrazolone 194a adds to indolones 213 to form spiro pyrano-pyrazoles 226, which possess herbicidal activity (88JIC277) (Scheme 86). 

Indandione 120 with indolones 213 forms pyrans 227 as the only products (89JHC1097, 08H(75)955) (Scheme 87). 

Chemical Class Dipropylaminoethyl indolone derivative Clinical Pharmacology ... 

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

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