Indeno isoquinolines

Nagarajan, M. Xiao, X. Antony, S. Kohlha-gen, G. Pommier, Y. Cushman, M. Design, synthesis, and biological evaluation of indeno-isoquinoline topoisomerase I inhibitors featuring polyamine side chains on the lactam nitrogen./. Med. Chem. 2003, 46, 5712-5724. 

A series of indeno[l,2-c]isoquinolines have been described [27] and INO-lOOl has been investigated in the clinic. Although the structure of INO-lOOl has not been reported, sulfonamide 28 is a representative structure (IC50 = lnM, EC5O = 10nM). CEP-9722 is in Phase I clinical trials, while its exact structure has not been disclosed, it is a prodrug of CEP-8983 (29) and patent applications highlight 30. Preclinical efficacy in combination with TMZ and camptothecin have been... 

The interaction between ammonia and l-R1-3-aryl-substituted ben-zo[c]pyrylium salts 30, as well as 3,4-diaryl-substituted indeno[e l,2-]-benzo[c]pyrylium, and other substituted cations having a similar fragment is more complicated, especially in hydroxyl-containing solvents. In these cases, mixtures in different ratios are obtained that contain isoquinolines 138, 3-hydroxy-3,4-dihydroisoquinolines 137, OR-adducts 109, anhydro-bases 119, diketones 29, a-naphthylamines 140, and a-naphthols 141 (88UP2). 

Details of the sequence of steps in the thionyl chloride-mediated transformation of 4-carboxy-3,4-dihydro-3-phenyl-l(2//)-isoquinolines into indeno[l,2-c]isoquinolones have been elucidated62 and it is confirmed that the dehydrogenation precedes the electrophilic cyclization [of (56)]. 

It has been claimed117 that 2-methyl-4-benzyTl,2-dihydroiso-quinolincs, e.g., 125, are cyclized to the 5,6,12,13-tetrahydro-l IH-indeno[l,2-c]isoquinoline (126) by mineral acid, but this reaction... 

A new synthetic route to the phthalide-isoquinoline and spiro-benzyl-isoquinoline alkaloids has been developed. The indeno[2,l-a]benzazepine (105),... 

The synthesis of the parent ring-system of the protopine alkaloids using Perkin s method has been described.224 The preparation of examples of the indeno[l,2-c]isoquinoline ring system (219), exhibited by a rearrangement product of cryptopine, has been described.225 The transformation of protopine to benzophenanthridine alkaloids will be described in Section 3 J. 

Moos WH, Gless RD, Rapoport H (1983) Codeine analogs - synthesis of 4a-aryldecahy-droisoquinolines containing nitrogen ring functionality and of octahydro-1 h-indeno[l,2,3-ef]isoquinolines - a total synthesis of codeine. J Org Chem 48 227-238 Toth JE, Euchs PL (1987) Syntheses via vinyl sulfones. 21. Total synthesis of dl-morphine. 

A soln. of 2-methyl-4-piperonyl-6,7-dimethoxy-l,2-dihydroisoquinoline in acetic acid containing coned. HCl refluxed 1.5 hrs. under Ng 3,4-dimethoxy-6-methyl-8,9-methylenedioxy-5,6,12,13-tetrahydro-l lH-indeno[l,2-c]isoquinoline. Y 75%. 

Oracin, 6-[2-(2-hydroxyethyl)aminoethyl]-5,ll-di-oxo-5,6-dihydrollH-indeno[l,2-c]isoquinoline, is a potent antineoplastic agent for oral use. Its biotransformation by rat liver microsomes to 3-hydro-xyoracin was stimulated by 3-methylcholanthrene-induced cytochrome P4501A, and decreased by the specific P4501A inhibitor a-naphthoflavone (Szo-tAkovA et al. 1999). 

Members of the cevanine subgroup have a benzo[4,5]indeno[l,2-/i]pyrido [l,2-6]isoquinoline skeleton (see Figure 1) and form the largest subgroup discussed in this chapter. 

One example of the cycloaddition of a 2-azaallenium salt 15 with diphenylacetylene is known, and the cycloadduct, 1 l//-indeno[l,2-c]isoquinoline salt 16, is obtained in 37 % yield... 

Microwave-assisted direct aiylation reactions were successfully employed in the synthesis of azafluoranthene alkaloids. Ponnala and Harding (2013) reported that direct aiylation reactions on a diverse set of phenyltetrahydroisoquinolines produced the indeno[l,2,3-ij]isoquinoline nucleus, required towards a high-yielding azafluoranthene synthesis. The method was used as a key step in the efficient preparation of the natural products rufescine and triclisine. This synthetic approach may be generally applicable to the preparation of natural and un-natural azafluoranthene alkaloids as well as azafluoranthene-like isoquinoline alkaloids. 

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