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Dual demeanour of norcantharidin derived dicarboxamides in acidic media: An insight
Institution:1. Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;2. Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;3. Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India;1. Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland;2. Institute of Physical and Theoretical Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland;1. Steroid Research Laboratory, Department of Chemistry, Aligarh Muslim University, Aligarh 202002, UP, India;2. Department of Chemistry, Faculty of Science, King Saud University, Riyadh 11451, Saudi Arabia;3. Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, Stuttgart 70569, Germany;1. Departamento de Química Orgánica and Centro de Innovación en Química Avanzada (ORFEO-CINQA), Facultad de Ciencias, Universidad de Alicante, 03080, Alicante, Spain;2. Instituto de Síntesis Orgánica, Facultad de Ciencias, Universidad de Alicante, 03080, Alicante, Spain;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No.38 Xueyuan Road, Haidian District, Beijing, 100191, China;2. Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK;3. Academy of Chinese Medical Sciences of Jilin Province, No.155 Chuangju Road, Changchun, 130012, China;4. Program in Molecular Therapeutics, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, United States;5. Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS, 66045, United States;6. Center for Computational Biology, University of Kansas, 2030 Becker Drive, Lawrence, KS, 66047, United States;1. Department of Chemistry, Taras Shevchenko National University of Kyiv, 01601, Ukraine;2. Department of Chemistry, University of Canterbury, P.B. 4800, Christchurch 8140, New Zealand;1. National Taras Shevchenko University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine;2. Enamine Ltd, Alexandra Matrosova Street 23, Kyiv 01103, Ukraine;3. STC ‘Institute for Single Crystals’, National Academy of Sciences of Ukraine, Lenina ave. 60, 61001 Kharkiv, Ukraine
Abstract:The hydrolytic stability of norcantharidine derived conformationally constrained diamides in acidic media is solely governed by the type of amide. Tertiary diamides underwent smooth acid catalyzed hydrolysis due to anchimeric assistance whereas other diamides were stable. This was corroborated from conformational proximity of the amide groups for anchimeric assistance based on single crystal X-ray structure analysis. Theoretical calculations on the diamide structures also predict the similar proximity of the diamides in those conformations. Thus norcantharidine based diamides could probably serve as promising systems for delayed release of certain types of drugs which possess secondary amine component as exemplified by the release of m-chlorophenylpiperazine at a pH range of 1–2.
Keywords:Amide hydrolysis  Neighbouring group participation  Theoretical calculation  X-ray crystal structure  Conformationally constrained diamide  Slow drug release
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