Computational and spectral studies of 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one)

Abstract

Detection and qualification of unknown impurities during commercial drug synthesis have been mandated by the regulatory authorities. 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo [d]azepin-2-one) in short IVA-9, is one such process-related impurity formed during the synthesis of cardiotonic drug Ivabradine. The structure and properties of this molecule have not been explored yet. A suggestive reaction route for the chance formation of IVA-9 during the commercial synthesis of parent drug molecule has been reported in this article. Further, the optimized geometry and vibrational studies have been computed using Gaussian 09. Experimental FTIR scan has also been performed and values show satisfactory consilience with the computational data. The frontier orbital energies and energy band gaps of the reaction fragments and products were computed. The evaluation of ADME parameters such as absorption, distribution, metabolism, and excretion are performed using SwissADME tool to assess the drug-likeness and medicinal chemistry friendliness. Six physiochemical parameters namely flexibility, lipophilicity, size, polarity, solubility and saturation and their critical limits are depicted using the bioavailability radar of the programme to provide insights into pharmacokinetic properties such as human gastrointestinal absorption (HIA), blood-brain-barrier (BBB) permeability, total polar surface area (TPSA) and inhibitor action to important cytochromes etc.

From Infection Clusters to Metal Clusters: Significance of the Lowest Occupied Molecular Orbital (LOMO)

“…. Using C j , eq 8 can be rewritten as 46 ε = HC C j j j (10) If one uses the adjacency matrix of A instead of H, eq 10 can be changed into…”

“…The two electrons occupying the HOMO are distinct from the other electrons in that they are essential to the reactivity of a molecule as they interact with the LUMO of another molecule. 1 This simplistic picture has made it possible to develop an understanding of a variety of physicochemical properties of molecules, including thermodynamic stability, 10 reorganization energies, 11 and electron transmission. 12 In this paper, we will focus on the lowest occupied molecular orbital (LOMO).…”

Preliminary investigation of drug impurities associated with the anti-influenza drug Favipiravir – An insilico approach

“…These parameters also give us a preclinical assessment of the overall toxicity of the lead molecules. ADME-based filtering studies help us to handpick the best druglike molecules and also help to minimize potential failures at an advanced stage, by avoiding the unsuitable candidates initially [34] , [35] . For better pharmacological efficacy, the selected drugs are expected to present inside the body in the right quantity for the right duration of time before getting excreted.…”

Computational, Spectral, and Bioavailability Studies of Venlafaxine Cyclic Impurity

“…To the best of our knowledge, the structure, properties, and assaying techniques of the title molecule have not been explored yet. As part of their studies of therapeutically important impurity molecules (28)(29)(30)(31)(32)(33), the authors propose to explore the structural and spectral properties of VEN-CI.…”