The discovery of long acting β2-adrenoreceptor agonists

Brown, Alan D.; Bunnage, Mark E.; Glossop, Paul A.; James, K.; Jones, Rhys D.O.; Lane, Charlotte A. L.; Lewthwaite, Russell A.; Mantell, Simon J.; Perros-Huguet, Christelle; Price, David A.; Trevethick, Michael A.; Webster, Rob

doi:10.1016/j.bmcl.2007.04.081

Cited by 39 publications

(42 citation statements)

References 16 publications

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“…These results are probably due to partial decomposition of the resin working at this rather high temperature. When the reaction was performed in toluene at reflux, a lower Pd leaching was detected, but competitive homocoupling of 4-bromoacetophenone to give 4,4'diacetylbiphenyl was observed (Table 3, entries [4][5][6].…”

Section: P As Catalyst Tri-mentioning

confidence: 97%

“…In the case of methyl 4-and 3-bromophenylacetates the corresponding N-styrylphthalimides 6h and 6i were obtained in 55-79% yields (Table 2, entries 23-26). It is worthy of note that the latter compound 6i, which is the main unit of the drug I [6] (Figure 2), was obtained with a high regio-and diastereoselectivity (up to 99/1). The activated 4-nitrobromobenzene furnished the insoluble product 6j, which precipitated in the reaction medium and was isolated in 71% yield (Table 2, entry 27).…”

Section: P As Catalyst Tri-mentioning

confidence: 98%

“…[2d] Although N-vinylphthalimide is commercially available, the main drawback found for this Heck acceptor is the control of the a-and b-regioselectivity, [2,3] which is due to the competition of cationic and neutral mechanisms, respectively, in electron-rich alkenes. [4] In addition, barylated N-vinylphthalimides are important compounds, [5] for instance, the metabolic drug I is a b2 adrenoceptor agonist, [6] compound II is a fungicide, [7] and III is a non-linear, optically active material [8] ( Figure 2). We have recently studied the Heck reaction [9] of electron-rich alkenes using Cy 2 NMe as base and 2 or palladacycles 3, 4, or 5 [10] (Figure 3) as catalysts under phosphine-free conditions.…”

Section: Introductionmentioning

confidence: 99%

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Regioselective Heck Reaction of N‐Vinylphthalimide: A General Strategy for the Synthesis of (E)‐N‐Styrylphthalimides and Phenethylamines

Alacid

Nájera

2008

Adv Synth Catal

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Abstract:The arylation of N-vinylphthalimide takes place at the b-position with aryl iodides, bromides and chlorides using palladium acetate [PdA C H T U N G T R E N N U N G (OAc) 2 ] or phenone oxime-derived palladacycles as catalysts under phosphine-free conditions. The reaction is succesfully carried out in organic solvents, such as DMF, in the presence of an organic base, such as dicyclohexylmethylamine, and with TBAB as additive at 120 8C under conventional or microwave heating. (E)-N-Styrylphthalimides are mainly obtained using a rather low palladium loading (0.05-1 mol%). Similar catalytic efficiency is observed using a Kaiser oxime resin-derived palladacycle, which allows reuse of the polymeric complex for three cycles. The high regioselectivity observed supports that these palladacycles work as a source of Pd(0) species operating mainly through a neutral mechanism. The syntheses of 2-thienylphenethylamine and mescaline have been performed by subsequent hydrogenation with Wilkinsons catalyst and hydrazinolysis.

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Section: P As Catalyst Tri-mentioning

confidence: 97%

Section: P As Catalyst Tri-mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Regioselective Heck Reaction of N‐Vinylphthalimide: A General Strategy for the Synthesis of (E)‐N‐Styrylphthalimides and Phenethylamines

Alacid

Nájera

2008

Adv Synth Catal

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“…The design and profile of a series of saligenin-containing LABAs has been described [46]. They have significantly longer durations of action than salmeterol and have the potential for a once-daily profile in humans.…”

Section: Las-100977mentioning

confidence: 99%

Emerging inhaled bronchodilators: an update

Cazzola¹,

Matera²

2009

European Respiratory Journal

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Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field.The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients.A variety of b 2 -agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development.The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.

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“…Deste modo, foi possível lançar no mercado, na década de 1990, outro fármaco com maior tempo de ação, o salmeterol (Serevent®). Adicionalmente, novas substâncias de ação seletiva e longa duração, como o formoterol (Symbicort®), estão sendo desenvolvidas e lançadas periodicamente a fi m de melhorar o tratamento da patologia (Brown et al, 2007;Barnes, 2006).…”

Section: Agonistas De Receptores -Adrenérgicosunclassified

Substâncias de origem vegetal potencialmente úteis na terapia da asma

Corrêa¹,

Melo²,

Costa³

2008

Rev. bras. farmacogn.

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RESUMO:A asma é uma doença infl amatória crônica, que representa um problema de saúde pública com altos números de óbitos e elevado impacto socioeconômico. A patologia é caracterizada pela fase imediata, mediada pela resposta aguda de células infl amatórias, e a tardia, que é responsável pela resposta com envolvimento de células específi cas do sistema imunológico. Atualmente, os principais tipos de fármacos utilizados no tratamento da asma são os broncodilatadores e agentes antiinfl amatórios, que aliviam os sintomas de broncoespasmo e diminuem a infl amação das vias aéreas. Entretanto, terapias com esses medicamentos não são totalmente efi cazes e provocam efeitos adversos. A escassez de fármacos seguros e o baixo acesso da população carente aos tratamentos utilizados estimulam a busca de novas substâncias potencialmente úteis no tratamento da asma. Produtos naturais de origem vegetal representam um grande potencial farmacológico contra asma, uma vez que podem fornecer moléculas diversas com mecanismos específi cos para tratamento e controle da patologia. A busca por terapias mais efi cientes e específi cas para o processo asmático mostra que a procura nos produtos naturais é promissora e possui um papel importante para a descoberta de novas terapias contra a asma.Unitermos: Asma, infl amação crônica, células Th2, plantas medicinais, produtos naturais, metabólitos secundários.ABSTRACT: "Natural products from plant origin potentially usefull in the asthma therapy". Asthma is a chronic infl ammatory disease, which represents a huge public health problem in developed and developing countries, has high death rates and elevated socioeconomic implications. The pathology is characterized by two different phases: the initial stage, mediated by acute infl ammatory cell response and the late phase, responsible for specifi c immune cells. Currently, the main drugs used for asthma treatment are bronchodilator and anti-infl ammatory agents, which mechanisms focus the relief of symptoms and attenuation of airway infl ammation. However, therapies with those drugs have side effects besides they are not totally effective. Poor accessibility in the development countries and scarcity of safety drugs lead the search for new drugs to asthma treatment. Herbal natural products have elevated pharmacological potential against asthma, once they provide several molecules with specifi c mechanisms for the pathology control and treatment. Thus, search in herbal natural products plays an important role to fi nd out specifi c and effective mechanisms.

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The discovery of long acting β2-adrenoreceptor agonists

Cited by 39 publications

References 16 publications

Regioselective Heck Reaction of N‐Vinylphthalimide: A General Strategy for the Synthesis of (E)‐N‐Styrylphthalimides and Phenethylamines

Regioselective Heck Reaction of N‐Vinylphthalimide: A General Strategy for the Synthesis of (E)‐N‐Styrylphthalimides and Phenethylamines

Emerging inhaled bronchodilators: an update

Substâncias de origem vegetal potencialmente úteis na terapia da asma

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