Adrenoceptor blocking agents. 2. 2-(.alpha.-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective .beta.2-adrenoceptor antagonists

Jain, P. C.; Khandelwal, Y.; Tripathi, O.

doi:10.1021/jm00199a012

Cited by 5 publications

(2 citation statements)

References 5 publications

(7 reference statements)

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“…While stimulation of the beta1-adrenergic receptor is responsible for the inotropic (contractile) function of cardiac myocytes, it initially seemed counterintuitive that beta1-receptor antagonists such as bisoprolol, metoprolol, and carvedilol could improve HF symptoms and prolonged life in patients with HF [1, 16–19]. Cardiac myocyte toxicity through excessive beta1-stimulation in fact involves a cascade of intracellular biochemical events including intracellular calcium overload, programmed cell death (apoptosis), and remodeling of the extracellular matrix [18, 24].…”

Section: What Work: Pharmacological Successes In Heart Failure Treatmentioning

confidence: 99%

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Howell

Cameron

2016

Cardiol J.

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Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality.

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Section: What Work: Pharmacological Successes In Heart Failure Treatmentioning

confidence: 99%

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Howell

Cameron

2016

Cardiol J.

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“…Aziridines are a rich source of important pharmaceuticals and adrenoceptor blocking agents (1). Publications on the preparation of aziridine-2-carboxylic acid esters from shortchain 2-bromo-2,3-unsaturated or 2,3-dibromo ester are reported (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2, 3 fatty aziridines

Ahmad

Osman

1984

J Americ Oil Chem Soc

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A new route for the synthesis of 2,3-aziridines is described. The reaction of methyl 2,3-dibromohexadecanoate (I1) with ammonia at 0 C gave methyl 2-bromohexadec-2-enoate (II1, ca. 93%). Compound III, on further treatment with ammonia at 25 C, gave methyl 2-aminohexadec-2-enoate (IV, ca. 5%), methyl trans-2,3-epiminohexadecanoate (V, ca. 64%), methyl cis-2,3-epiminohexadecanoate (VI, ca 24%) and trans-2,3-epirninohexadecamide (Vll, ca 3%). The structures were established with the help of elemental analyses and infrared (IR), nuclear magnetic resonance (NMR) and mass spectral analyses.

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ChemInform Abstract: ADRENOCEPTOR BLOCKING AGENTS. 2. 2‐(α‐HYDROXYARYLMETHYL)‐3,3‐DIMETHYLAZIRIDINES, A NEW CLASS OF SELECTIVE β2‐ADRENOCEPTOR ANTAGONISTS

Jain¹,

Khandelwal²,

Tripathi³

1978

Chemischer Informationsdienst

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Adrenoceptor blocking agents. 2. 2-(.alpha.-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective .beta.2-adrenoceptor antagonists

Cited by 5 publications

References 5 publications

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Synthesis of 2, 3 fatty aziridines

ChemInform Abstract: ADRENOCEPTOR BLOCKING AGENTS. 2. 2‐(α‐HYDROXYARYLMETHYL)‐3,3‐DIMETHYLAZIRIDINES, A NEW CLASS OF SELECTIVE β2‐ADRENOCEPTOR ANTAGONISTS

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