Design and Synthesis of Indole and Tetrahydroisoquinoline Hydantoin Derivatives as Human Chymase Inhibitors

Alagille, David; Pfeiffer, Bruno; Scalbert, Elizabeth; Ferry, Gilles; Boutin, Jean A.; Renard, Pierre; Viaud‐Massuard, Marie‐Claude

doi:10.1080/14756360310001650200

Cited by 10 publications

(6 citation statements)

References 13 publications

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“…Tricyclic compounds containing a hydantoin moiety were obtained starting from tetrahydroisoquinoline and analogs. The reaction of tetrahydroisoquinoline-3-carboxylic acid 357−360 or its carboxylate derivatives, 357,361 which indeed act as an amino acid analogues, and potassium cyanate has been reported. The indole analog was also prepared in the same way.…”

Section: Tetrahydroisoquinoline Hydantoinsmentioning

confidence: 99%

“…The indole analog was also prepared in the same way. 357,359 Otherwise, the ureido derivatives could be prepared by N-activation of the tetrahydroisoquinoline ring with CDI or triphosgene and subsequent addition of an amine before their cyclization into hydantoins (Scheme 57). 362−364 9.2.2.…”

Section: Polycyclic Fused 135-trisubstituted Hydantoinsmentioning

confidence: 99%

“…The reaction of tetrahydroisoquinoline-3-carboxylic acid − or its carboxylate derivatives, , which indeed act as an amino acid analogues, and potassium cyanate has been reported. The indole analog was also prepared in the same way. , Otherwise, the ureido derivatives could be prepared by N- activation of the tetrahydroisoquinoline ring with CDI or triphosgene and subsequent addition of an amine before their cyclization into hydantoins (Scheme ). − …”

Section: Fused Hydantoinsmentioning

confidence: 99%

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Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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The review highlights the hydantoin syntheses presented from the point of view of the preparation methods. Novel synthetic routes to various hydantoin structures, the advances brought to the classical methods in the aim of producing more sustainable and environmentally friendly procedures for the preparation of these biomolecules, and a critical comparison of the different synthetic approaches developed in the last twelve years are also described. The review is composed of 95 schemes, 8 figures and 528 references for the last 12 years and includes the description of the hydantoin-based marketed drugs and clinical candidates.

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Section: Tetrahydroisoquinoline Hydantoinsmentioning

confidence: 99%

Section: Polycyclic Fused 135-trisubstituted Hydantoinsmentioning

confidence: 99%

Section: Fused Hydantoinsmentioning

confidence: 99%

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Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

et al. 2017

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“…Despite the elegant synthesis of tetrasubstituted alkenes via Co, Ru, and Rh ,, catalysis, our process stands as an unprecedented example of Rh(III)-catalyzed synthesis of tetrasubstituted alkenes carrying a gem -difluoromethylene functionality at the α-position. Considering the prevalence of the imidazo[1,5- a ]indole and tetrasubstituted alkene scaffolds in bioactive molecules (Figure S1), , our protocol is quite appealing, as it allows the divergent synthesis of the challenging C1-alkynylated quaternary imidazo[1,5- a ]indoles and α,α-difluoromethylene tetrasubstituted alkenes via rhodium catalysis.…”

mentioning

confidence: 99%

Rh(III)-Catalyzed Divergent Synthesis of Alkynylated Imidazo[1,5-a]indoles and α,α-Difluoromethylene Tetrasubstituted Alkenes

Zhao

Jin

et al. 2021

Org. Lett.

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Herein, we report the divergent synthesis of alkynylated imidazo[1,5-a]indoles and α,α-difluoromethylene tetrasubstituted alkenes through Rh(III)-catalyzed [4 + 1] annulation/alkyne moiety migration and C–H alkenylation/DG migration, respectively. This protocol features tunable product selectivity, excellent chemo-, regio-, and stereoselectivity, broad substrate scope, moderate to high yields, good tolerance of functional groups, and mild redox-neutral conditions.

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“…Polycyclic isoquinoline compounds are well known as anticancer [1] and antitumour [2] agents, and as acetylcholinesterase [3] and human chymase inhibitors [4]. Recently, the synthesis and biological properties of isoquinolines spirofused with carbocycles and heterocycles in position 4 have been reviewed [5].…”

mentioning

confidence: 99%

A novel synthesis of 2-substituted 2H-imidazo[1,5-b]isoquinoline-1,5-diones by in situ desulfurization

Khurana

Sharma

2008

Chem Heterocycl Comp

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reported with nickel boride in dry methanol at ambient temperature.Keywords: nickel boride, polycyclic isoquinoline, desulfurization.Polycyclic isoquinoline compounds are well known as anticancer [1] and antitumour [2] agents, and as acetylcholinesterase [3] and human chymase inhibitors [4]. Recently, the synthesis and biological properties of isoquinolines spirofused with carbocycles and heterocycles in position 4 have been reviewed [5]. In view of their importance, we decided to explore the synthesis of a new class of substituted imidazo[1,5-b]isoquinoline-1,5-dione derivatives by reductive desulfurization of 2-substituted 3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones with nickel boride. Nickel boride has been used successfully for desulfurization of the C=S group flanked by the NH group of dialkyl thioureas [6], 2(1H)-benzimidazolinethiones [6], 1,3-diaryl-2-thioxo-2H,5H-1,3-dihydropyrimidine-4,6-diones [6], 2-thioxo-4(3H)-quinazolinones [7], and 4-oxo-2-thioxo-5H-pyrano-[2,3-d]pyrimidines [8] by our research group besides reductions of other functionalities [9][10][11][12][13][14][15][16].We report herein a convenient and efficient synthesis of 2-substituted 2H-imidazo[1,5-b]isoquinoline-1,5-diones 2a-f with nickel boride in dry methanol at ambient temperature following a simple workup procedure. Nickel boride was prepared in situ from anhydrous nickel chloride and sodium borohydride in dry methanol. Various 2-substituted 3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones 1a-f underwent complete reductive desulfurization with nickel boride using a 1:7:7 or 1:9:9 molar ratio of substrate/NiCl 2 /NaBH 4 in dry methanol and yielded the corresponding 2-substituted 2H-imidazo[1,5-b]isoquinoline-1,5-diones 2a-f in nearly quantitative yields. The starting 2-substituted 3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones were prepared by condensation of 2-formylbenzoic acid with 3-substituted 2-thiohydantoins [17]. N N O S O R N N O O R N O NiCl 2 / NaBH 4 MeOH, r. t. 1a-f 2a-f 1,2 a R = H, b R = Me, c R = i-Pr, d R = Ph, e R = CH 2 Ph, f R = CH 2 _________________________________________________________________________________________

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Design and Synthesis of Indole and Tetrahydroisoquinoline Hydantoin Derivatives as Human Chymase Inhibitors

Abstract: The synthesis of new potential inhibitors of human chymase is described. Treatment of dihydroimidazo[1,5-a]indole and [1,5-b]isoquinoline-dione with thioaryl followed by oxidation gave the N-arylsulfonylmethyl of polycyclic hydantoin derivatives 3, 5 and 6.

Cited by 10 publications

References 13 publications

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Rh(III)-Catalyzed Divergent Synthesis of Alkynylated Imidazo[1,5-a]indoles and α,α-Difluoromethylene Tetrasubstituted Alkenes

A novel synthesis of 2-substituted 2H-imidazo[1,5-b]isoquinoline-1,5-diones by in situ desulfurization

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