11H-isoindolo[2,1 -a]indol-11-ones: novel rearrangement products from the attempted preparation of 2-(2-diethylaminomethylphenyl)isatogens

Hooper, M.; Imam, Syed Haider

doi:10.1039/p19850001583

Cited by 15 publications

(6 citation statements)

References 3 publications

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“…The required known [26][27][28] 4-(dialkylaminoalkoxy)anilines were prepared by the general method of Kaye 26 as modified by Buchi, 29 involving alkylation of sodium 4-nitrophenoxide by known substituted alkyl chlorides, [30][31][32] followed by catalytic reduction. Similarly, 1-methyl-4-(p-aminophenyl)piperazine 33 was obtained by alkylation of 1-methylpiperazine with 4-nitrofluorobenzene, followed by catalytic reduction (Pd/C).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60^c^-src

et al. 2000

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7-substituted 3-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-ones are potent inhibitors of protein tyrosine kinases, with some selectivity for c-Src. The compounds were prepared by condensing 4, 6-diaminonicotinaldehyde with 2,6-dichlorophenylacetonitrile and selectively converting the 2- and 7-amino groups of the product to hydroxy and fluoro groups, respectively, by prolonged diazotization in 50% aqueous fluoboric acid. N-Methylation, followed by treatment with aliphatic diamines, aromatic amines, or their derived lithium anions, gave the desired compounds. Selected isomeric 1, 8-naphthyridin-2(1H)-ones were also prepared in order to evaluate the relative contributions of both ring A aza atoms of the related pyrido[2,3-d]pyrimidin-7(8H)-ones to the inhibitory activity. The compounds were evaluated for their ability to prevent phosphorylation of a model substrate by c-Src, FGF-1 receptor, and PDGF-beta receptor enzymes. Overall, there was a high degree of correlation of the activities against the different kinases, with c-Src being generally the most sensitive to structural changes. 1, 6-Naphthyridin-2(1H)-one analogues bearing basic aliphatic side chains [7-NH(CH(2))(n)()NRR, 7-NHPhO(CH(2))(n)()NRR, or 7-NHPhN(CH(2))(4)NMe] were the most potent against c-Src (IC(50)s of 10-80 nM), showing good selectivity with respect to PDGFR (10-300-fold) but less with respect to FGFR. The 1, 6-naphthyridin-2(1H)-ones showed broadly similar activity to the analogous pyrido[2,3-d]pyrimidin-7(8H)-ones, whereas the 1, 8-naphthyridin-2(1H)-ones were at least 10(3)-fold less potent. These results, indicating that the 3-aza atom in the pyrido[2, 3-d]pyrimidin-7(8H)-ones is mandatory, whereas the 1-aza atom is not, support the published binding model for these compounds to c-Src (J. Med. Chem. 1998, 41, 1752), where the 3-aza and 2-NH atoms form a bidentate H-bond donor-acceptor motif that interacts with Met341 and the 1-aza atom is not involved in specific binding interactions.

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Section: Chemistrymentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60^c^-src

et al. 2000

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“…However, the synthesis of functionalized indoles still presents a major challenge in organic synthesis. Isoindolo[2,1- a ]indoles are a class of these functionalized indoles that have been synthesized by employing classical synthetic organic, photochemical, radical, , and palladium-mediated , methodologies. The classical synthetic, photochemical, and radical methods that have been reported all afford relatively low yields of the tetracyclic products and have yet to be employed on targets bearing much functionality.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Isoindolo[2,1-a]indoles by the Palladium-Catalyzed Annulation of Internal Acetylenes

2000

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A wide variety of substituted isoindolo[2,1-alpha]indoles have been prepared via annulation of internal alkynes by imines derived from o-iodoanilines in the presence of a palladium catalyst. This methodology provides an extremely efficient route for the synthesis of these tetracyclic heterocycles from readily available starting materials. The mechanism of this interesting annulation process appears to involve (1) oxidative addition of the aryl iodide to Pd(0), (2) alkyne insertion, (3) addition of the resulting vinylic palladium intermediate to the C-N double bond of the imine, (4) either electrophilic palladation of the resulting sigma-palladium intermediate onto the adjacent aromatic ring derived from the internal alkyne or oxidative addition of the neighboring aryl carbon-hydrogen bond, and (5) reduction of the tetracyclic product and Pd(0). A variety of internal acetylenes have been employed in this annulation process in which the aromatic ring of the alkyne contains either a phenyl or a heterocyclic ring.

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“…Isoindoloindolone derivatives are reported as potent ligands of MT 3 . 5 The third melatonin binding site, MT 3 , is an enzyme, quinone reductase-2 and not a usual seven transmembrane domains receptor. Hydroxyisoindoloindolone derivative 2a has subnanomolar affinity for the melatonin binding site MT 3 .…”

Section: Biological Activitymentioning

confidence: 99%

“…5 The third melatonin binding site, MT 3 , is an enzyme, quinone reductase-2 and not a usual seven transmembrane domains receptor. Hydroxyisoindoloindolone derivative 2a has subnanomolar affinity for the melatonin binding site MT 3 . Chloroisoindoloindolone derivative 2b, amidoisoindoloindolone derivative 2c, and aminoisoindoloindolone 2d show DNA binding ability and non-specific interference with the topoisomerase-I catalytic cycle (Figure 2).…”

Section: Biological Activitymentioning

confidence: 99%

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Isoindoloindolones - biological activities and syntheses

Kadam¹,

Tilve

2015

Arkivoc

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11H-isoindolo[2,1 -a]indol-11-ones: novel rearrangement products from the attempted preparation of 2-(2-diethylaminomethylphenyl)isatogens

Abstract: Die Isatogene (IV), deren Synthese durch Cyclisierung der o‐Nitrophenyl‐aryl‐acetylene (III) (die als instabile Öle anfallen) angestrebt wurde, konnten nicht isoliert werden.

Cited by 15 publications

References 3 publications

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60^c^-src

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60^c^-src

Synthesis of Isoindolo[2,1-a]indoles by the Palladium-Catalyzed Annulation of Internal Acetylenes

Isoindoloindolones - biological activities and syntheses

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11H-isoindolo[2,1 -a]indol-11-ones: novel rearrangement products from the attempted preparation of 2-(2-diethylaminomethylphenyl)isatogens

Abstract: Die Isatogene (IV), deren Synthese durch Cyclisierung der o‐Nitrophenyl‐aryl‐acetylene (III) (die als instabile Öle anfallen) angestrebt wurde, konnten nicht isoliert werden.

Cited by 15 publications

References 3 publications

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60c-src

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60c-src

Synthesis of Isoindolo[2,1-a]indoles by the Palladium-Catalyzed Annulation of Internal Acetylenes

Isoindoloindolones - biological activities and syntheses

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Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60^c^-src

Synthesis and Structure−Activity Relationships of 7-Substituted 3-(2,6-Dichlorophenyl)-1,6-naphthyridin-2(1H)-ones as Selective Inhibitors of pp60^c^-src