Delving into the Latest Updates on Milveterol Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Milveterol, Milveterol hydrochloride (USAN), 米维特罗

+ [6]

Target

β2-adrenergic receptor

Mechanism

β2-adrenergic receptor agonists(Beta-2 adrenergic receptor agonists)

Therapeutic Areas

Immune System DiseasesRespiratory Diseases

Active Indication

AsthmaPulmonary Disease, Chronic Obstructive

Inactive Indication-

Originator Organization

GSK Plc

Innoviva, Inc.

Active Organization

Innoviva, Inc.

Inactive Organization

GSK Plc

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC25H30ClN3O4

InChIKeyQQPHRRSYJMOQOC-DKIIUIKKSA-N

CAS Registry804518-03-4

Ebola virus is the etiological agent of a severe hemorrhagic fever with a high mortality rate. As the only protein exposed on the surface of viral particles, the spike glycoprotein GP is the unique target for neutralizing monoclonal antibodies. In this study, we demonstrate the strong neutralization capacity of the monoclonal antibody #3327 and characterize its activity. GP residues that are required for recognition and neutralization were found to be located both in the internal fusion loop and in the receptor-binding domain. Analysis of Ebola virus entry in the presence of #3327 allows us to hypothesize that this antibody binds to the virus particle before internalization and endosomal processing of GP and likely prevents the final viral fusion step. Importantly, #3327 is able to block entry of virions bearing GP that contain the Q508 escape mutation common to a number of virus-neutralizing antibodies, and therefore provides future perspectives for treatment strategies against Ebola virus infection.

28 May 2015·Journal of Medicinal ChemistryQ1 · MEDICINE

Bronchodilating Drugs for Chronic Obstructive Pulmonary Disease: Current Status and Future Trends

Q1 · MEDICINE

Article

Author: Montuschi, Paolo ; Ciabattoni, Giovanni

Inhaled bronchodilators, including long-acting muscarinic receptor antagonists (LAMA) and long-acting β2-adrenoreceptor agonists (LABA), are the mainstay of pharmacological treatment of stable chronic obstructive pulmonary disease (COPD). Among approved LAMA, tiotropium bromide, glycopyrronium bromide, and umeclidinium bromide are administered once daily, whereas aclidinium bromide is administered every 12 h. New LAMA are under development for COPD. Among the approved LABA, indacaterol has a 24 h duration of action, whereas salmeterol and formoterol require twice-daily administration. New once-daily LABA, including vilanterol, olodaterol, milveterol, carmoterol, and abediterol, are in development. LAMA/LABA fixed dose combinations (FDCs) provide the convenience of two bronchodilators with different mechanism of action in a single inhaler. Indacaterol/glycopyrronium, umeclidinium/vilanterol, and olodaterol/tiotropium FDCs have been approved or are under approval and are likely to become a standard pharmacological strategy for COPD. Inhaled dual-pharmacology compounds, combining muscarinic antagonism and β2-agonism (MABA) in a single molecule, potentially provide additive or synergistic bronchodilation over either inhaled antimuscarinic or β2-agonist monotherapy.

01 Jun 2014·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: Pfeiffer, Juergen W ; Yu, Cecile ; Church, Timothy J ; Jacobsen, John R ; Pulido-Rios, Teresa M ; Moran, Edmund J ; Aggen, James B ; Thomas, G Roger ; Klein, Uwe

A series of potent β2-adrenoceptor agonists incorporating a biarylamine secondary binding group was identified. The previously reported milveterol (5), identified by a multivalent approach and containing a typical β2-agonist primary binding group linked via a phenethylamine linker to a hydrophilic secondary binding group, served as an initiation point. A more hydrophobic set of secondary binding groups was explored, prepared rapidly from a common intermediate by Buchwald-Hartwig amination. TD-5471 (25), a potent and selective full agonist of the human β2-adrenoceptor, was identified as the most promising agent. It is potent, with slow onset in an in vitro guinea pig trachea model and shows a dose-dependent and long duration of action in an in vivo guinea pig model of bronchoprotection. TD-5471 is structurally differentiated from milveterol and its long duration of action is consistent with a correlation with hydrophobicity observed in other long-acting β2-agonist discovery programs.

100 Deals associated with Milveterol Hydrochloride

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