The benzodiazepine story

Sternbach, L. H.

doi:10.1021/jm00187a001

Cited by 406 publications

(208 citation statements)

References 56 publications

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“…The detailed theoretical analysis of the interaction of 3,5-dimethyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one (1e) with 2-sulfinylaminobenzoyl chloride (4) showed that the acylationcyclization reaction can be described as sequential three-step process. Firstly, the pre-reactive reactant complex is activated to intermediate with stabilized Van der Waals interaction between Cl and H atoms.…”

Section: Theoretical Studiesmentioning

confidence: 99%

“…22 A new approach to the synthesis of the title compounds is shown in Scheme 2. It is based on the use of the activated form of anthranilic acid, 2-sulfinylaminobenzoyl chloride (4). The high reactivity of this reagent towards imines, amides and amines allows its use in the synthesis of various compounds.…”

Section: Synthetic Studiesmentioning

confidence: 99%

“…3 Therefore, the benzodiazepine nucleus is a well-studied pharmacophoric scaffold that has emerged as a core structure unit of various biological activities and the research in this area is very active. 4 It is well documented that the pharmacological activity could be increased when an additional heterocyclic ring is fused to the heptatomic diazepine nucleus. 5 Thus, considerable attention has been directed towards the synthesis of polycyclic 1,4-benzodiazepines, as well as the 1,5-isomers.…”

Section: Introductionmentioning

confidence: 99%

“…6,13,14 Fused quinazolinones are important heterocyclic compounds with widespread occurrence in alkaloids possessing diverse biological activity. 15 Various methods for the synthesis of these alkaloids encompassing a quinazolino [1,4]benzodiazepine moiety in their skeleton have been developed and numerous research papers have recently appeared. 16,17 As part of our current studies on the development of efficient methods for the preparation of polycyclic 1,5-benzodiazepines we investigated the synthesis of quinazolino [1,5]benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

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Novel synthesis of quinazolino[3,2-a][1,5]benzodiazepines: an experimental and computational study

Janciene¹,

Javorskis²,

Mikulskiene³

et al. 2015

Arkivoc

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[ [1,5]benzodiazepin-13(5H)-one derivatives were synthesized in a one-step sequential acylation-cyclization reaction with a simple procedure from an appropriate 5-substituted 3-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one and 2-sulfinylaminobenzoyl chlorides. The mechanism of the heterocyclization reaction was studied by the DFT method using the B3LYP functional and 6-31+G(d, p) basis set.

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Section: Theoretical Studiesmentioning

confidence: 99%

Section: Synthetic Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel synthesis of quinazolino[3,2-a][1,5]benzodiazepines: an experimental and computational study

Janciene¹,

Javorskis²,

Mikulskiene³

et al. 2015

Arkivoc

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“…Os derivados 1,4-benzodiazepínicos pertencem a uma importante classe terapêutica de fármacos com atividade ansiolítica, hipnótica, anticonvulsivante e relaxante muscular 77 . De maneira semelhante aos derivados ciproeptadínicos, as 1,4-benzodiazepinas também apresentam atropoisomerismo, conforme relato de Gilman et al 78 , que descreveram as duas possíveis conformações do diazepam 82 e, por inferência, de outros análogos apresentado o mesmo esqueleto heterocíclico.…”

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Atropoisomerismo: o efeito da quiralidade axial em substâncias bioativas

Santos¹,

Pinheiro²,

Sodero³

et al. 2007

Quím. Nova

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Recebido em 26/9/05; aceito em 30/3/06; publicado na web em 26/9/06 ATROPISOMERISM: THE EFFECT OF THE AXIAL CHIRALITY IN BIOACTIVE COMPOUNDS. Atropisomerism is a special kind of stereoisomeric relationship that arises from the freezing of a certain conformation of an organic molecule, associated with a high rotational barrier about a single covalent bond. Atropisomerism has been originally described in orto-functionalyzed biphenyl derivatives, but a lot of other organic functionalities can present this structural phenomenon, characterized by the presence of chiral properties in compounds that don't present classical stereogenic centers. Atropisomeric compounds, intermediates and catalysts have well-know importance in organic synthesis, but the influence of the axial chirality in substances able to modulate biological systems is still not very exploited in drug design and development. In this context, the present account describes the importance of this structural property in the medicinal chemistry of different classes of bioactive compounds or therapeutic agents, emphasizing how atropisomerism could affect the molecular recognition of a ligand or a prototype by the target bioreceptor.Keywords: atropisomerism; atropisomerism of drugs; stereoselective molecular recognition. INTRODUÇÃOO fenômeno conhecido como atropoisomerismo, denominação oriunda da palavra grega atropos (i.e. sem rotação), é atribuído a um tipo de estereoisomerismo característico de sistemas onde a rotação livre em torno de uma ligação simples é impedida, produzindo uma barreira energética suficientemente elevada, de modo a permitir o isolamento ou simplesmente a detecção dos diferentes rotâmeros, chamados atropoisômeros 1,2 . Este tipo de isomeria axial é caracterizada pela atividade ótica promovida por um eixo de ligação, não necessitando que a substância apresente carbono estereogênico como elemento de quiralidade. O fenômeno foi observado pela primeira vez por Christie e Kenner 3 , após a resolução dos atropoisômeros do ácido 6,6'-dinitro-2,2'-difênico 1, os quais não se mostraram interconversíveis à temperatura ambiente (Figura 1).A nomenclatura de substâncias que apresentam quiralidade axial pode ser atribuída como R ou S pela aplicação das regras de prioridade de Cahn-Ingold-Prelog 4,5 , conforme exemplificado na Figura 2. A partir da projeção da estrutura vista na direção do eixo de ligação do sistema bifenílico, deve-se definir a ordem de prioridade dos grupos funcionais, iniciando por aqueles mais próximos ao observador e, em seguida, atribuir a configuração absoluta R ou S com base no sentido da rotação produzida quando se caminha do substituinte de maior prioridade para o de menor prioridade. Apesar de ser opcional, a descrição da configuração absoluta de estereoisômeros atropoisoméricos deve ser acompanhada pela introdução do prefixo a, i.e. aR ou aS, visando distinguí-los de outros tipos de compostos oticamente ativos. De maneira alternativa, os compostos atropoisoméricos podem ser vistos como hélices e suas configurações descritas...

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Thermal cycloaddition reaction of symmetrical and unsymmetrical α‐diazo‐β‐diketones with 4‐aryl‐2‐methyl‐2,3‐dihydro‐1,5‐benzothia/diazepines

Jin

1999

Heteroatom Chemistry

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Symmetrical and unsymmetrical α‐diazo‐β‐diketones undergo thermal Wolff rearrangements to generate α‐carbonylketenes to participate as dienes in Diels–Alder reactions with 4‐aryl‐2‐methyl‐2,3‐dihydro‐1,5‐benzothia/diazepines to give, whereapplicable, regiospecific cycloadducts, 4a,5,6,12‐tetrahydro‐1H/1H,7H‐1,3‐oxazino[3,2‐d][1,5]benzo‐thia/diazepin‐1‐ones. A mechanism of formation of the regiospecific cycloadducts is suggested. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 35–40, 1999

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The benzodiazepine story

Cited by 406 publications

References 56 publications

Novel synthesis of quinazolino[3,2-a][1,5]benzodiazepines: an experimental and computational study

Novel synthesis of quinazolino[3,2-a][1,5]benzodiazepines: an experimental and computational study

Atropoisomerismo: o efeito da quiralidade axial em substâncias bioativas

Thermal cycloaddition reaction of symmetrical and unsymmetrical α‐diazo‐β‐diketones with 4‐aryl‐2‐methyl‐2,3‐dihydro‐1,5‐benzothia/diazepines

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