Synthesis and SAR of a novel, potent and structurally simple LTD4 antagonist of the quinoline class

Sprecher, Andreas von; Gerspacher, Marc; Beck, Andreas; Kimmel, S.; Wiestner, Hansruedi; Anderson, Gary P.; Niederhauser, U; Subramanian, N.; Bray, M.A.

doi:10.1016/s0960-894x(98)00137-1

Cited by 29 publications

(4 citation statements)

References 9 publications

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“…[1][2][3] The structural core of quinoline is often found in more complex natural products 4 and is frequently associated with biological activity, such as anticancer, 5 antifungal, 6 HIV-1 integrase inhibitors, 7 HIV protease inhibitors 8 antileishmanial activity, 9 NK-3 receptor antagonists 10 and pLT antagonists. [11][12][13] Our objectives were to synthesize a series of quinoline derivatives substituted at position 1 and 2 by a spacer linked with a series of amino acids and dipeptides as pLT antagonists regarded as important mediators of human bronchial asthma 14 .…”

Section: Introductionmentioning

confidence: 99%

Convenient syntheses of methyl 2-[2-(3-acetyl-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)acetamido] alkanoates and their O-regioisomers

Ali¹,

Fathalla²,

Rayes³

2008

Arkivoc

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Methyl 2-[2-(3-acetyl-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)acet-amido] alkano-ate 7; Oregioisomers 12 and N-substituted dipeptides 14 were efficiently prepared by azide coupling of amino acid esters with the azide derivatives 5, 11 and 13, respectively. Further the N-substituted ester 7 reacted with N 2 H 4 .H 2 O to give the hydrazide 8 which was condensed with furan-2-carbaldehyde to exhibit the hydrazone 9.

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Section: Introductionmentioning

confidence: 99%

Convenient syntheses of methyl 2-[2-(3-acetyl-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)acetamido] alkanoates and their O-regioisomers

Ali¹,

Fathalla²,

Rayes³

2008

Arkivoc

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“…The quinoline nucleus occurs in several natural compounds (cincona alkaloids) and pharmacologically active substances displaying a broad range of biological activity . The biological activity of quinoline compounds has been found in the form of antiasthmatic, antibacterial, antiinflammatory and antihypertensive properties. In addition to the medicinal applications, quinolines have been employed in the study of bioorganic and bioorganometallic processes .…”

Section: Introductionmentioning

confidence: 99%

Ionic Liquid-Promoted Regiospecific Friedlander Annulation: Novel Synthesis of Quinolines and Fused Polycyclic Quinolines

et al. 2003

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Several room-temperature ionic liquids (ILs) based on 1-butylimidazolium salts with varying anions were synthesized and evaluated for the preparation of biologically active substituted quinolines and fused polycyclic quinolines using the Friedlander heteroannulation reaction. On screening, 1-butylimidazolium tetrafluoroborate [Hbim]BF4 was found to be the best ionic liquid for the heteroannulation reaction, and the reasons to this effect are well explained. The reactions proceed very well under relatively mild conditions without any added catalyst. The IL acts as a promoter for this regiospecific synthesis and can be recycled. By this green approach, various quinolines were prepared in excellent yields and purity and well-characterized.

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“…Adicionalmente, os dados de SAR desta classe sugeriram a importância do padrão de substituição do anel aromáti-co central, visto que regioisômeros de posição são significativamente menos ativos [105][106][107][108] (Figura 12). Face à complexidade de fenômenos bioquímicos e celulares envolvidos na fisiopatologia da asma, associações terapêuticas tem sido empregadas na prática clínica, para seu tratamento.…”

Section: E/ou Fpl 55712unclassified

Agentes antiasmáticos modernos: antagonistas de receptores de leucotrienos cisteínicos

2002

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Recebido em 9/8/01; aceito em 4/10/01 MODERN ANTIASTHMATIC DRUGS: CYSTEINYL LEUKOTRIENES RECEPTORS ANTAGONISTS. In the early 1990s numerous clinical trials with antileukotriene drugs confirmed the hypothesis that cysteinyl leukotrienes are important bronchoconstrictor agents in asthma. Newly released"antiasthmatic medications include antileukotriene agents which function either by blocking the interaction of leukotrienes with receptors or by inhibiting leukotriene synthesis. Representatives of cysteinyl leukotriene receptors antagonists are zafirlukast (7), montelukast (8) and pranlukast (9). The bronchodilator efficacy and antiinflammatory property of antileukotriene drugs provided the main impetus behind their introduction as the first novel class of asthma therapy in more than 20 years.Keywords: antileukotrienes; antiasthmatic drugs; leukotriene. INTRODUÇÃOA asma constitui um estado inflamatório crônico geralmente acompanhado de sinais clínicos familiares, que se somam a uma das características principais do processo de obstrução reversível das vias aéreas, o broncoespasmo 1 . Estes sinais, representados por dispnéia, tosse, espirro intermitente, opressão torácica e broncoconstrição, são decorrentes de processos fisiológicos como edema, recrutamento e ativação de células inflamatórias, aumento da secreção de muco e contração da musculatura lisa brônquica, seguida de hipertrofia e hiperplasia muscular [1][2][3] . A asma brônquica é uma fisiopatologia genericamente classificada em asma extrínseca e intrínseca, classificação que decorre da participação (ou não) de mecanismos alergênicos envolvendo a imunoglobulina E (IgE) [4][5][6][7][8] . O processo asmático é basicamente dividido em duas fases, a saber: a) fase imediata, causada principalmente por espasmo do músculo liso bronquial, caracterizando a resposta de broncoconstrição típica desta fisiopatologia; b) fase tardia, ocorre em tempo variável após a exposição ao estímulo antigênico, ocasionada essencialmente por uma resposta inflamatória aguda que normalmente progride a um estado inflamatório crônico [9][10][11] . Esta última fase é responsável pela principal característica da asma, i.e., a hiperreatividade brônquica, que se refere à sensibilidade anormal a ampla faixa de estímulos como substâncias químicas irritantes, ar frio, fármacos, alérgenos, poluentes atmosféricos, entre outros 12 . Ademais, a resposta asmática de fase tardia é caracterizada por uma inflamação do tipo eosinofílica, que se relaciona de forma direta com o desenvolvimento da hiperreatividade brônquica [13][14][15] . PREVALÊNCIA E MORTALIDADE DA ASMA BRÔNQUICAA asma representa uma das condições patológicas crônicas de maior incidência no mundo contemporâneo. Era uma fisiopatologia rara no ínicio do século, entretanto, sua prevalência em países industrializados tem crescido assustadoramente, assumindo proporções epidêmi-cas, acometendo ca. 155 milhões de pessoas por todo mundo [16][17][18] . O custo do tratamento de pacientes asmáticos é substancial, estimando-se gastos da ordem de US$ 6 ...

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Synthesis and SAR of a novel, potent and structurally simple LTD4 antagonist of the quinoline class

Cited by 29 publications

References 9 publications

Convenient syntheses of methyl 2-[2-(3-acetyl-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)acetamido] alkanoates and their O-regioisomers

Convenient syntheses of methyl 2-[2-(3-acetyl-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)acetamido] alkanoates and their O-regioisomers

Ionic Liquid-Promoted Regiospecific Friedlander Annulation: Novel Synthesis of Quinolines and Fused Polycyclic Quinolines

Agentes antiasmáticos modernos: antagonistas de receptores de leucotrienos cisteínicos

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