Synthesis and Characterization of Impurities of Barnidipine Hydrochloride, an Antihypertensive Drug Substance

Cheng, Zhi Gang; Dai, Xu Yong; Li, Li Wei; Wan, Qiong; Ma, Xiang; Xiang, Guang Ya

doi:10.3390/molecules19011344

Cited by 10 publications

(5 citation statements)

References 6 publications

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“…Over the years numerous methodologies have been developed for the production of enantiopure 1,4-DHP derivatives, such as stereoselective synthesis using chiral auxiliaries and chiral cyclocondensation partners [41], catalytic asymmetric synthesis [42], resolution of diastereomeric 1,4-DHP salts derived from chiral acids or bases [43], enzyme catalysed kinetic resolution, or asymmetrisation of enzymatically labile esters activated spacer groups [9,[44][45][46].…”

Section: Stereoselective Synthesis Of 14-dihydropyridinesmentioning

confidence: 99%

Recent Approaches to Chiral 1,4-Dihydropyridines and their Fused Analogues

et al. 2020

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The purpose of this review is to highlight recent developments in the synthesis of chiral 1,4-dihydropyridines and their fused analogues. 1,4-Dihydropyridines are among the most active calcium antagonists that are used for the treatment of hypertension. Enantiomers of unsymmetrical 1,4-dihydropyridines often show different biological activities and may have even an opposite action profile. Hantzsch synthesis usually produces racemic mixtures of unsymmetrical 1,4-dihydropyridines. Therefore, the development of stereoselective synthesis of 1,4-dihydropyridines is one of the priorities of medicinal chemistry. Over the years, numerous methodologies have been developed for the production of enantiopure 1,4-dihydropyridines, such as stereoselective synthesis using chiral auxiliaries and chiral cyclocondensation partners, chromatographical methods, resolution of diastereomeric 1,4-dihydropyridine salts, enzyme catalysed kinetic resolution, or asymmetrisation of ester groups of 1,4-dihydropyridines. These approaches have been studied in detail and are relatively well established. The catalytic asymmetric approach holds the greatest promise in delivering the most practical and widely applicable methods. Substantial progress has been made toward the development of enantioselective organocatalytic methods for the construction of the chiral dihydropyridines. However, most of them do not provide a convenient way to pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates. Organocatalytic enantioselective desymmetrisation of prochiral 1,4-dihydropyridine-3,5-dicarbaldehydes also has great promise in the synthesis of pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates.

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Section: Stereoselective Synthesis Of 14-dihydropyridinesmentioning

confidence: 99%

Recent Approaches to Chiral 1,4-Dihydropyridines and their Fused Analogues

et al. 2020

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“…It has been assessed by various researchers who have provided effective therapeutic agents for managing various diseases and disorders (Rucins et al, 2020). Barnidipine hydrochloride (BRN) is a potent third‐generation 1,4‐dihydropyridine antagonist—chemically, (3 S )‐1‐benzyl‐3‐pyrrolidinylmethyl(4 S )‐2,6‐dimethyl‐4‐(3‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate hydrochloride, used clinically as an antihypertensive agent for the management of various cardiovascular disorders (Cheng et al, 2014; Teramura et al, 1995). It demonstrates virtual aqueous insolubility, i.e.…”

Section: Introductionmentioning

confidence: 99%

Exploring an experimental combination of analytical quality by design and green analytical chemistry approaches for development of HPTLC densitometric protocol for the analysis of barnidipine hydrochloride

Shirkhedkar

Chaudhari

2021

Biomedical Chromatography

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An experimental combination of analytical quality by design and green analytical chemistry approaches is introduced to develop an high‐performance thin‐layer chromatography (HPTLC) approach to quantify barnidipine hydrochloride in the pharmaceutical matrix. The analytical quality by design approach was introduced to green analytical chemistry to enhance protocol knowledge while ensuring efficiency and reducing environmental impacts, energy consumption and analyst visibility. This analytical approach was systematically addressed by exploring failure mode effect analysis, risk assessment and optimization design. Subsequently, a screening of primary variables was performed to select the aptest proportion of solvents in the mobile phase resulting from the principles of green analytical chemistry. Failure mode effect analysis and a risk assessment study were attempted to estimate the critical method parameters (CMPs). The influence of the CMPs on critical analytical attributes, i.e. retention factor and peak area, was assessed through a screening design. A response surface methodology was then executed for the critical analytical attributes as a concern of the determined CMPs, and the conditions for excellent resolution were determined using a desirability procedure. The established protocol was validated in compliance with the International Conference on Harmonization guideline Q2(R1) and showed excellent specificity and sensitivity.

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“…All antihypertensive drugs with dihydropyridine structure have shown strict photolability. This vulnerability is to be held in high regard, as it involves loss of therapeutic effect and is potentially dangerous due to the probability of phototoxic reactions [ 6 , 7 ]. The chemical process of photodegradation generally consists in the oxidation of the dihydropyridine ring with the formation of the pyridine derivative.…”

Section: Introductionmentioning

confidence: 99%

“…Returning to the ground state, free radicals or photoproducts, potentially toxic to cell membranes or DNA, can be formed [ 20 , 21 ]. For some DHP drigs, data and results on phototoxicity have been reported [ 6 , 7 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

1,4-Dihydropyridine Antihypertensive Drugs: Recent Advances in Photostabilization Strategies

2019

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The 1,4-dihydropyridine (DHP) drugs are nowadays the most used drugs in the treatment of hypertension. However, all the structures in this series present a significant sensitivity to light, leading to the complete loss of pharmacological activity. This degradation is particularly evident in aqueous solution, so much so that almost all DHP drugs on the market are formulated in solid preparations, especially tablets. The first and main process of photodegradation consists in the aromatization of the dihydropyridine ring, after which secondary processes can take place on the various substituents. A potential danger can result from the formation of single oxygen and superoxide species that can in turn trigger phototoxic reactions. Several strategies for the photostabilisation of DHP drugs have been proposed in recent years, in particular with the aim to formulate these drugs in liquid preparations, as well as to limit any toxicity problems related to light degradation. This review summarizes and describes the main aspects of the studies conducted in recent years to obtain photostable formulations of DHP drugs.

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Synthesis and Characterization of Impurities of Barnidipine Hydrochloride, an Antihypertensive Drug Substance

Cited by 10 publications

References 6 publications

Recent Approaches to Chiral 1,4-Dihydropyridines and their Fused Analogues

Recent Approaches to Chiral 1,4-Dihydropyridines and their Fused Analogues

Exploring an experimental combination of analytical quality by design and green analytical chemistry approaches for development of HPTLC densitometric protocol for the analysis of barnidipine hydrochloride

1,4-Dihydropyridine Antihypertensive Drugs: Recent Advances in Photostabilization Strategies

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