Pyrido[1′,2′:1,2]pyrimido[5,4‐<i>d</i>]indoles. A new heterocyclic ring system

This paper describes the synthesis of two 4‐amino‐5H‐pyrimido[5,4‐b]indoles 5, 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole 6, two 1,2,4‐triazolo[4,3‐c]pyrimido[5,4‐b]indoles 8, and tetrazolo[4,5‐c]pyrimido[5,4‐b]indole 10. Starting with ethyl 3‐aminoindole‐2‐carboxylate 1, 5H‐pyrimido[5,4‐b]indol‐4‐one 2 was obtained (80%) by condensing with formamide. Reactions of 2 with phosphorus oxychloride and phosphorus pentasulfide gave respectively, 4‐chloro‐5H‐pyrimido[5,4‐b]indole 3 (70%) and 5H‐pyrimido[5,4‐b]indole‐4‐thione 4 (80%). Compound 3 reacted with amines (morpholine, piperidine) to give the respective 4‐amino‐5H‐pyrimido[5,4‐b]‐indoles 5, and compound 4 reacted with hydrazine to give 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole 6 (80%). Two hydrazones of 6 (benzylidene, isopropylidene) 7 were also prepared (90%). Compound 6 reacted with formic and acetic acids to give (65–75%) the respective 1,2,4‐triazolo[4,3‐c]pyrimido[5,4‐b]indoles 8 and with nitrous acid to give tetrazolo[4,5‐c]pyrimido[5,4‐b]indole 9 (85%). All the new compounds 2 to 9 were characterized by elemental analysis and spectral data (ir, nmr).

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“…Compound 1 (mp 150-152O) was prepared by reported methods from 2-aminobenzonitrile [12] or ethyl indole-2-carboxylate [14].…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole and related compounds

Monge

Palop

GONI

et al. 1986

Journal of Heterocyclic Chem

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“…Merck Kieselgel 60F 254 plates were used for TLC, and Merck Silica gel 60 (0.063–0.100) for column chromatography. Ethyl 3‐aminoindole‐2‐carboxylate ( 7 ) was prepared by a literature method [20].…”

Section: Methodsmentioning

confidence: 99%

One‐step ring‐closure procedure for 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indole derivatives with Lawesson's reagent. The fifth dihydro‐1,3‐thiazino[b]indole isomer

Csomós

Fodor

Bernáth

et al. 2011

Journal of Heterocyclic Chem

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We report a convenient approach for the synthesis of a new ring system: 4,5-dihydro-1,3-thiazino [5,4-b]indoles. The procedure involves the use of Lawesson's reagent in the presence of silica to achieve the one-step ring-closure reactions of 2-benzoylamino-3-hydroxymethylindole intermediates to furnish 4,5-dihydro-2-aryl-1,3-thiazino [5,4-b]indoles. 2-Phenylimino-1,3-thiazino[5,4-b]indoles were obtained via the corresponding 3-phenylthiourea-2-carboxylic acid ester derivatives by chemoselective reduction of the ester group, followed by ring closure under acidic conditions. The structures of the novel products were elucidated by IR, 1 H-NMR, and 13 C-NMR spectroscopy, including 2D-HMQC, 2D-HMBC, and DEPT measurements.

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“…The starting aminoester 5 , which was prepared according to the Unangst's method, was reacted with triethylortho esters of formic, acetic, or propionic acids to afford the corresponding iminoethers 6 − 8 . Products 6 − 8 were reacted with 2-ethanolamine or 3-amino-1-propanol to obtain tricyclic alcohols 9 − 14 .…”

Section: Chemistrymentioning

confidence: 99%

New Pyrimido[5,4-b]indoles as Ligands for α₁-Adrenoceptor Subtypes

et al. 2003

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A new series of compounds were designed as structural analogues of the alpha(1)-AR ligand RN5 (4), characterized by a tricyclic 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione system connected through an alkyl chain to a phenylpiperazine (PP) moiety. These compounds were synthesized and tested in binding assays on human alpha(1A)-AR, alpha(1B)-AR, and alpha(1D)-AR subtypes expressed in HEK293 cells. Several structural modifications were performed on the PP moiety, the tricyclic system, and the connecting alkyl chain. Many of the new molecules showed a preferential affinity for the alpha(1D)-AR subtype. Some compounds, including 39 and 40, displayed substantial alpha(1D)-AR selectivity with respect to alpha(1A)-AR, alpha(1B)-AR, serotonergic 5-HT(1A), 5-HT(1B), 5-HT(2A), and dopaminergic D(1) and D(2) receptors. Two conformationally rigid analogues of 4, useful for studying the architecture of the receptor/ligand complex, were also prepared and tested. A subset of the new compounds was then used to evolve a preliminary pharmacophore model for alpha(1D)-AR antagonists, based on a more generalized model we had developed for alpha(1)-AR antagonists. This new model rationalized the relationships between structural properties and biological data of the pyrimido[5,4-b]indole compounds, as well as other compounds.

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Pyrido[1′,2′:1,2]pyrimido[5,4‐d]indoles. A new heterocyclic ring system

Cited by 27 publications

References 6 publications

Synthesis of 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole and related compounds

Synthesis of 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole and related compounds

One‐step ring‐closure procedure for 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indole derivatives with Lawesson's reagent. The fifth dihydro‐1,3‐thiazino[b]indole isomer

New Pyrimido[5,4-b]indoles as Ligands for α₁-Adrenoceptor Subtypes

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Pyrido[1′,2′:1,2]pyrimido[5,4‐d]indoles. A new heterocyclic ring system

Cited by 27 publications

References 6 publications

Synthesis of 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole and related compounds

Synthesis of 4‐hydrazino‐5H‐pyrimido[5,4‐b]indole and related compounds

One‐step ring‐closure procedure for 4,5‐dihydro‐1,3‐thiazino[5,4‐b]indole derivatives with Lawesson's reagent. The fifth dihydro‐1,3‐thiazino[b]indole isomer

New Pyrimido[5,4-b]indoles as Ligands for α1-Adrenoceptor Subtypes

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New Pyrimido[5,4-b]indoles as Ligands for α₁-Adrenoceptor Subtypes