Multivalent design of long-acting β2-adrenoceptor agonists incorporating biarylamines

Jacobsen, John R.; Aggen, James B.; Church, Timothy; Klein, Uwe; Pfeiffer, Juergen; Pulido-Rios, T; Thomas, Glyn; Yu, Cecile; Moran, Edmund J.

doi:10.1016/j.bmcl.2014.04.069

Cited by 10 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…indacaterol, require once-a-day dosing ( 17 ). Other β 2 -agonists, which are currently being developed as once-a-day treatment, include vilanterol ( 18 ), olodaterol ( 19 ), carmoterol ( 20 ), abediterol ( 21 ), milveterol ( 22 ) and TD-5471 ( 23 ). The clinical effectiveness of these drugs for the treatment of COPD is not surprising given their similarities in efficacy in activating the canonical Gs protein pathway leading to elevation of cyclic AMP ( 24 ).…”

Section: Labamentioning

confidence: 99%

Pharmacology of novel treatments for COPD: are fixed dose combination LABA/LAMA synergistic?

Spina

2015

European Clinical Respiratory Journal

View full text Add to dashboard Cite

Bronchodilators are mainstay for the symptomatic treatment of chronic obstructive pulmonary disease (COPD) and the introduction of long-acting bronchodilators has led to an improvement in the maintenance treatment of this disease. Various clinical trials have evaluated the effects of fixed dose long-acting β2-agonists (LABA)/long-acting anti-muscarinics (LAMA) combinations and documented greater improvements in spirometry but such improvements do not always translate to greater improvements in symptom scores or reduction in the rates of exacerbation compared with a single component drug. An analysis of whether this significantly greater change in spirometry with combination therapy is additive or synergistic was undertaken and is the subject of this review. Bronchodilators are not disease modifiers and whilst glucocorticosteroids have been shown to reduce rates of exacerbation in moderate to severe COPD, the increase risk of pneumonia and bone fractures is a motivation enough to warrant developing novel anti-inflammatory and disease-modifying drugs and with the expectation of positive outcomes.

show abstract

Section: Labamentioning

confidence: 99%

Pharmacology of novel treatments for COPD: are fixed dose combination LABA/LAMA synergistic?

Spina

2015

European Clinical Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…TD-5471 was developed by modification of the 4-aminophenethylamine linking group of the milveterol scaffold. 72 In the guinea pig trachea assay, it has a slow onset of action with pEC 50 of 8.7±0.1. TD-5471's selectivity for the human β 2 -adrenergic receptor is comparable to formoterol with a β 2 pEC 50 of 9.4±0.4, intrinsic activity of 83±9%, and functional selectivity β 2 /β 1 of 56 and β 2 /β 3 of 100.…”

Section: Td-5471mentioning

confidence: 99%

<p>Ultra Long-Acting β-Agonists in Chronic Obstructive Pulmonary Disease</p>

Burkes¹,

Panos²

2020

JEP

View full text Add to dashboard Cite

Introduction Inhaled β-agonists have been foundational medications for maintenance COPD management for decades. Through activation of cyclic adenosine monophosphate pathways, these agents relax airway smooth muscle and improve expiratory airflow by relieving bronchospasm and alleviating air trapping and dynamic hyperinflation improving breathlessness, exertional capabilities, and quality of life. β-agonist drug development has discovered drugs with increasing longer durations of action: short acting (SABA) (4–6 h), long acting (LABA) (6–12 h), and ultra-long acting (ULABA) (24 h). Three ULABAs, indacaterol, olodaterol, and vilanterol, are approved for clinical treatment of COPD. Purpose This article reviews both clinically approved ULABAs and ULABAs in development. Conclusion Indacaterol and olodaterol were originally approved for clinical use as monotherapies for COPD. Vilanterol is the first ULABA to be approved only in combination with other respiratory medications. Although there are many other ULABA’s in various stages of development, most clinical testing of these novel agents is suspended or proceeding slowly. The three approved ULABAs are being combined with antimuscarinic agents and corticosteroids as dual and triple agent treatments that are being tested for clinical use and efficacy. Increasingly, these clinical trials are using specific COPD clinical characteristics to define study populations and to begin to develop therapies that are trait-specific.

show abstract

“…TD-5471 -сильный и селективный полный аго-нист человеческих β 2 -адренорецепторов, был иден-тифицирован как наиболее перспективный агент в серии потенциальных β 2 -агонистов, содержащих вторично связанную группу биариламина [65].…”

Section: обзорыunclassified

Progress and Prospects for Long-Acting Β 2 -Agonists in the Treatment of Chronic Obstructive Pulmonary Disease

Mario¹,

Ermanno²,

Ora³

et al. 2018

BCCM

View full text Add to dashboard Cite

Статья итальянских авторов дает полное пред-ставление о развитии адреномиметиков ультрадли-тельного действия при ХОБЛ. Ценность статьи -во всесторонней оценке проблемы, отсутствии ангажированности и тенденциозности в изложении проблемы. Мы надеемся, что знакомство с русской версией статьи обогатит наших читателей новыми знаниями и расширит их мировоззрение. Реферат. Лечение хронической обструктивной болезни легких (ХОБЛ), как правило, предполагает назначение комбинации лекарственных препаратов, одним из которых зачастую является агонист β 2 -адренорецепторов. Цель данной статьи -представить информацию об агонистах β 2 -адренорецепторов длительного действия (ультра-ДДВА) -современную форму препаратов, обеспечивающую высокую приверженность пациентов к лечению, благодаря упрощенной схеме приема 1 раз в сут. Материал и методы. Проанализированы совре-менные литературные данные об агонистах β 2 -адренорецепторов. В частности, новейшие данные о применении ультра-ДДВА в лечении ХОБЛ, а также вопросы безопасности препарата для сердечно-сосудистой системы. Результаты и их обсуждение. Рассматривается инновационный метод назначения фиксированных доз ДДБА в комбинации с антихолинергическими препаратами длительного действия (ДДАХ) и/или с ингаляционными кор-тикостероидами, а также новейших препаратов ультра-ДДВА, находящихся на этапах клинического исследования и доклинической разработки. Выводы. Огромный интерес к разработке новых агонистов β 2 -адренорецепторов длительного действия значительно снизился за последние годы. Тем не менее ультра-ДДВА считаются одним из основных компонентов лечения ХОБЛ в комбинации с другими классами препаратов (ДДАХ и ингаляционные кортикостероиды), которые в настоящее время находятся на этапе внедрения для регулярного использования. Vergata, Via Montpellier,1, Italy, 00133, Rome, Abstract. Aim. The treatment of chronic obstructive pulmonary disease (COPD) is generally based on the assumption of drug combinations in which β 2 -agonists are commonly included. Ultra-LABAs were developed to induce a greater adherence to the treatment as a result of the simplification of treatment with the reduction of the daily dose to be taken. Material and methods. We analyzed the current literature data on β 2 -adrenergic agonists. The potential positioning of ultra-LABAs in the treatment of COPD and their cardiovascular safety is discussed according to the new information on the topics. Results and discussion. The novel fixed-dose combinations of ultra-LABAs with LAMAs and/or ICSs are examined, as well as the novel ultra-LABAs under clinical development and the ultra-LABAs in preclinical development. PROGRESS AND PROSPECTS FOR LONG-ACTING β 2 -AGONISTS IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

show abstract

Multivalent design of long-acting β2-adrenoceptor agonists incorporating biarylamines

Cited by 10 publications

References 23 publications

Pharmacology of novel treatments for COPD: are fixed dose combination LABA/LAMA synergistic?

Pharmacology of novel treatments for COPD: are fixed dose combination LABA/LAMA synergistic?

<p>Ultra Long-Acting β-Agonists in Chronic Obstructive Pulmonary Disease</p>

Progress and Prospects for Long-Acting Β 2 -Agonists in the Treatment of Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About