A Facile, Improved Synthesis of Sildenafil and Its Analogues

Reddy, A. Venugopal; Garaga, Srinivas; Takshinamoorthy, Chandiran; Peruri, Badarinadh Gupta; Naidu, A.

doi:10.3390/scipharm84030447

Cited by 12 publications

(10 citation statements)

References 10 publications

(10 reference statements)

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“…Lastly, upon the hydrolysis of the latter with sodium hydroxide, lisinopril 47 was obtained in pure form. 86 Enalapril 51, commercialized under the brand name Vasotec among others, is a drug, employed for the treatment of high blood pressure, kidney disease caused by diabetes and heart failure in which is frequently used with a diuretic, such as furosemide. 90 Enalapril was patented in 1978, and approved as prescribed drug, coming to market in 1984.…”

Section: Five-membered Heterocyclesmentioning

confidence: 99%

“…Lisinopril 47, is a drug of the angiotensin-converting enzyme (ACE) inhibitor family which is used, primarily in the treatment of hypertension, heart failure, and frequently utilized after heart attack. 86 Lisinopril 47, chemically is named as N 2 -[(1 S )-1-carboxy-3-phenylpropyl]- l -lysyl- l -proline, but sold under the brand name of PRINVIL® provided by Merck. Lisinopril 47 was patented in 1978, and approved for medical use in the United States in 1987.…”

Section: Synthesis Of Nitrogen Prescribed Drugs Havingmentioning

confidence: 99%

“…Lastly, upon the hydrolysis of the latter with sodium hydroxide, lisinopril 47 was obtained in pure form. 86 …”

Section: Synthesis Of Nitrogen Prescribed Drugs Havingmentioning

confidence: 99%

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Prescribed drugs containing nitrogen heterocycles: an overview

2020

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Section: Five-membered Heterocyclesmentioning

confidence: 99%

Section: Synthesis Of Nitrogen Prescribed Drugs Havingmentioning

confidence: 99%

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Prescribed drugs containing nitrogen heterocycles: an overview

2020

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“…Our process for the synthesis of sildenafil citrate 1 is shown in Based on the synthetic process of sildenafil citrate, there is a possibility of the formation of sildenafil sulfonyl esters due to the usage of alcohol and its intermediates like sildenafil sulfonyl chloride (4) and sildenafil sulfonic acid (3). So many references [9][10][11][12] are available for sildenafil-related substances and its Sildenafil sulfonyl methyl ester 6 was prepared in two ways, i.e., reacting sildenafil sulfonyl chloride 4 with methanol in the presence of pyridine in dichloromethane gives compound 6 and the other way [13] is treating sildenafil sulfonic acid 3 with trimetyl orthoformate in methanol (as shown in Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

Identification, synthesis, and characterization of potential genotoxic impurities of sildenafil citrate drug substance

Reddy¹,

Musunuri

Reddy

et al. 2020

Futur J Pharm Sci

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Background Sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specifil phophodiesterase type 5 (PDE5). Sildenafil enhances the effect of nitric oxide by inhibiting phosphodiesterase type 5, which is responsible for the degradation of cGMP in the corpus cavernosum. The possible genotoxic impurities of sildenafil were synthesized, i.e., sildenafil sulfonyl methyl ester, sildenafil sulfonyl ethyl ester, and sildenafil sulfonyl isopropyl ester. The present work describes the synthesis and characterization of these sulfonyl ester compounds related to sildenafil. Results All the synthesized sildenafil sulfonyl esters have proved to be beneficial for the pharmaceutical industry in view of the regulatory importance. Conclusion A simple, efficient, and repeatable method was developed for the preparation of sildenafil sulfonyl esters in view of the regulatory importance of the potential genotoxic impurities in the active pharmaceutical ingredient. A detailed study of various impurities in sildenafil was conducted. Different process-related sulfonyl esters in sildenafil were identified, synthesized, and characterized by using various spectroscopic techniques like liquid chromatography-mass spectrometry (LCMS), mass, 1H NMR, and FT-IR. These efforts to synthesize and characterize them effectively have proved to be beneficial.

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“…[34] This molecule has been a significant contributor to Pfizer's revenues since 1998. [35] Sildenafil citrate (Viagra) has a remarkable success story for fulfilling the green chemistry objectives [36] by replacing MC in the commercial synthetic process. The modified process used thionyl chloride in stoichiometric quantities in toluene (chlorosulphonation step) as the reaction solvent so that toluene can be used as the extraction solvent after the reaction is quenched with water.…”

Section: Case 1: Sildenafil Citrate Commercial Synthetic Processmentioning

confidence: 99%

Efforts to Replace Methylene Chloride in Pharmaceutical Process Chemistry

Yogesh¹,

Srivastava

Mulik

2023

Macromolecular Symposia

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Methylene chloride (MC) or dichloromethane is a halogenated organic solvent of choice used in many chemical industries such as pharmaceutical, insecticide, paint, and polymer industries. Several health hazards associated with the use of MC are known to us through available literature. MC is reported to be a potential neurotoxic, cardiotoxic, cancer-causing, and tissue-damaging agent. Inhalation and direct skin contact are the major routes of exposure to MC in occupational environments. Most government agencies and environment, health and safety forums throughout the world have recognized MC as a hazardous solvent and have kept strict regulatory control on the usage of MC. MC is a Class 2 solvent as per ICH guidelines. This review article presents some case studies where MC has been replaced in commercial synthetic processes and column chromatography by other solvents and solvent mixtures, demonstrating that it is possible to either reduce the usage or replace MC in process chemistry. Many industrial and academic efforts have brought in place several solvent selection guides helpful for effectively replacing MC from existing or planned synthetic processes. Sustainable and environment-friendly synthetic processes can be developed by implementing the concept of green chemistry, such as replacing the use of MC in the existing chemical processes and avoiding the use of MC in future chemical processes. Successful introduction of MC-free chemical processes in the pharmaceutical industry can surely be achieved with continuous efforts in this direction.

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A Facile, Improved Synthesis of Sildenafil and Its Analogues

Cited by 12 publications

References 10 publications

Prescribed drugs containing nitrogen heterocycles: an overview

Prescribed drugs containing nitrogen heterocycles: an overview

Identification, synthesis, and characterization of potential genotoxic impurities of sildenafil citrate drug substance

Efforts to Replace Methylene Chloride in Pharmaceutical Process Chemistry

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