Application of Ugi three component reaction for the synthesis of quinapril hydrochloride

Borase, Bhushan B; Godbole, Himanshu M.; Singh, Girij Pal; Upadhyay, Pritesh R.; Trivedi, Anurag; Bhat, Varadaraj G; Shenoy, Gautham G.

doi:10.1080/00397911.2019.1682168

Cited by 9 publications

(6 citation statements)

References 7 publications

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“…Moreover, it is indicated as an adjunctive therapy for heart failure. [168] Godbole et al [168] synthesized quinapril hydrochloride through a sequence of reactions, where an U-3CR was the key step. Therefore, benzyl-2-isocyano-3-phenyl propanoate, acetaldehyde and ethyl-2-amino-4-phenylbutanoate were treated with TiCl 4 (5 mol-%) as the catalyst in methanol.…”

Section: Post Modifications Of the U-3crmentioning

confidence: 99%

The Ugi Three‐Component Reaction; a Valuable Tool in Modern Organic Synthesis

2020

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The Ugi three component reaction (U‐3CR) is a variation of the famous Ugi reaction, discovered almost 60 years ago. Today it is somehow neglected, compared to the classical variation, although the α‐aminoamides, derived from this reaction, have been utilized as inhibitors for various targets and even commercial drugs, offering improved pharmacokinetic properties. In this review, we are describing the scope and limitations of the reaction with a special focus on the developed catalytic protocols, the bioactive compounds, and drugs which are based on the reaction and finally the post modifications that have been reported in order to access drug‐like and privileged scaffolds. A special focus is given to the 3D solid state conformations of the U‐3CR derivatives.

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Section: Post Modifications Of the U-3crmentioning

confidence: 99%

The Ugi Three‐Component Reaction; a Valuable Tool in Modern Organic Synthesis

2020

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“…Este pró-fármaco, que é ativado por metabolismo à sua forma ativa, um diácido, através da hidrólise do grupo éster, é usado no tratamento da hipertensão, pertencendo ao grupo dos inibidores da enzima conversora da angiotensina (IECA), considerado o grupo terapêutico de primeira escolha para esta patologia crónica [46]. A sua síntese através da reação de Ugi permite a formação de um precursor com a cadeia α-amino amida, uma característica estrutural de vários fármacos da classe dos IECA, de forma rápida e eficaz, num total de quatro passos reacionais (Esquema 8) [47].…”

Section: Um Caso Particular De Rmc -A Reação De Ugiunclassified

“…Esquema 8 -Síntese de quinapril iniciada por uma reação de Ugi de três componentes [47]. mental, com alguns detalhes sobre o isolamento e purificação dos compostos, o que permite fazer uma comparação sobre a sustentabilidade dos dois processos de síntese desta molécula, em escala piloto (> 1 g).…”

Section: Sustentabilidade E Rmc: O Exemplo Da Lacosamidaunclassified

Reações Multicomponente – Uma Ferramenta Valiosa na Descoberta e Produção de Fármacos

Brandão¹,

Burke²,

Piñeiro³

2020

BSPQuimica

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“…[6] The valuable contribution of the Ugi reaction in the field of drug discovery and development can be confirmed by the number of active pharmaceutical ingredients (APIs) which can be prepared using this MCR (directly or in the preparation of one of their precursors). [7] Some of the most relevant examples include the antiepileptic drugs levetiracetam [8] and lacosamide, [9] local anesthetic lidocaine, [10] antiplatelet clopidogrel, [11] HMG-CoA reductase inhibitor atorvastatin, [12] antiretroviral indinavir, [13] antihypertensive quinapril, [14] and antiparasitic praziquantel. [15] Isatin (1H-Indole-2,3-dione) is a privileged structure in plethora of biological activities, being inclusively present in several commercialized drugs, such as ropinirole and ziprasidone.…”

Section: Introductionmentioning

confidence: 99%

Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties

et al. 2021

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Multicomponent reactions (MCRs) are a valuable tool for the sustainable synthesis of new molecules in a fast, effective and eco-friendly manner, leading to the generation of structurally diverse libraries. Their application in synthetic organic chemistry and medicinal chemistry, in combination with privileged scaffolds, is gaining momentum in recent years. The Ugi reaction is one of the most widely used MCRs in medicinal chemistry, and it is even used for the synthesis of several active pharmaceutical ingredients. Isatin, known for its biological activities and synthetic versatility, has been vastly used in several MCRs, however it was rarely used in combination with the Ugi reaction. Herein we report the first library of isatin-based Ugi 4 component reaction (U4CR) derivatives. Reaction optimization and scope were thoroughly explored, as well as mechanistic insights were obtained using DFT calculations. The resulting library was evaluated in what concerns its druglike properties, pharmacokinetic profile assessment in silico and antiproliferative activity in vitro, with several compounds bearing interesting druglike properties. Biological screening against six tumor cell lines, showed that the majority of the compounds display antiproliferative activity in the low and sub-micromolar range, with the achievement of nanomolar activity (0.1 nM, 6.5 nM and 5.4 nM against HBL-100, HeLa and WiDr, respectively) for the more active compound.

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Application of Ugi three component reaction for the synthesis of quinapril hydrochloride

Cited by 9 publications

References 7 publications

The Ugi Three‐Component Reaction; a Valuable Tool in Modern Organic Synthesis

The Ugi Three‐Component Reaction; a Valuable Tool in Modern Organic Synthesis

Reações Multicomponente – Uma Ferramenta Valiosa na Descoberta e Produção de Fármacos

Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties

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