专利号:US-8426630-B2 优先权日:2009-08-31 标题:Method and apparatus for continuous flow synthesis of ibuprofen 发明人:MCQUADE D TYLER; BOGDAN ANDREW; POE SARAH LIHOA 权利人:MCQUADE D TYLER; BOGDAN ANDREW; POE SARAH LIHOA; UNIV FLORIDA STATE RES FOUND 摘要:A multi-step method for the continuous synthesis of ibuprofen or a synthetic precursor of ibuprofen is provided that does not require any intermediate purification or isolation steps and uses reagents compatible with downstream reactions. According to some embodiments, a method is provided wherein isobutylbenzene and a propionyl compound may be converted into a first product in a first Friedel Crafts acylation reaction. The first product may then be converted into a second product in a 1,2-aryl migration reaction. Finally, the second product may be converted into ibuprofen in a hydrolysis reaction. The present invention also provides a method wherein only the first and second reaction steps or only the second and third reaction steps are performed. An apparatus is also provided having two or more microreactors and two or more junctions in particular arrangements for the synthesis of ibuprofen or a synthetic precursor of ibuprofen.
专利号:US-5248815-A 优先权日:1991-12-27 标 题 :Stereo-selective synthesis of 2-aryl-propionic acids of high optical purity by using chiral oxazolines 发明人:PARADIES HENRICH H 权利人:PARADIES HENRICH H 摘要:The present invention relates to a stereospecific chemical synthesis of optically pure enantiomers of 2-aryl-alkanoic acids, especially those of the biologically active (S)-aryl-propionic acids, in good chemical yields, useful for preparing large quantities thereof, and having a high optical purity.
专利号:US-2012029226-A1 优先权日:2009-02-06 标题:Method for the synthesis of chiral alpha-aryl propionic acid derivatives 发明人:KAPTEIN BERNARDUS; VLIEG ELIAS; NOORDUIN WILLEM LIEUWE 权利人:KAPTEIN BERNARDUS; VLIEG ELIAS; NOORDUIN WILLEM LIEUWE 摘要:The present invention provides a method for the synthesis of optically pure α-aryl propionic acid derivatives comprising subjecting the corresponding racemic α-aryl propionic acid derivatives to high sheer or impact forces, such as grinding.
专利号:US-2023212204-A1 优先权日:2020-01-16 标题:Reagents and their use for modular enantiodivergent synthesis of c-p bonds 发明人:XU DONGMIN; RIVAS-BASCÓN NAZARET; KNOUSE KYLE W; PADIAL NATALIA; ZHENG BIN; VANTOUROUT JULIEN; SCHMIDT MICHAEL; EASTGATE MARTIN D; BARAN PHI 权利人:BRISTOL MYERS SQUIBB CO; SCRIPPS RESEARCH INST 摘要:The disclosure describes chiral P(V)-based reagents and their uses for the modular, scalable, and stereospecific synthesis of chiral phosphines, phosphine oxides and particular oligonucleotides.
专利号:US-11897914-B2 优先权日:2021-11-29 标题 :Synthesis of 2′ protected nucleosides 发明人:POON WING C; ZOU RUIMING; LAU ALDRICH N K; YU DAVID; Du Gengyu; YAO YUN-CHIAO; ZHAO GANG 权利人:HONGENE BIOTECH CORP 摘要:Embodiments of the present application relate to the preparation of 2′-O-protected nucleoside phosphoramidites and conjugation of the 2′-O-protected nucleoside to a solid support. More specifically, the present application relates to nucleosides having a hydroxy protecting group at the 2′ position that reduces migration to the 3′ position during RNA (e.g., mRNA) synthesis and can be readily removed under mild conditions without the use of toxic metal-containing reagents. Methods of using the nucleosides described herein in RNA synthesis are also disclosed.
专利号:WO-2021033174-A1 优先权日:2020-10-31 标题 :Synthesis, characterization, and biological evaluation of ibuprofen derivative against colon and breast cancer cell-lines 发明人:AL-OBAIDI ZAID MAHDI JABER; AL-ANI AWATEF A IBRAHIM; SHAHEED DHURGHAM QASIM 权利人:AL OBAIDI ZAID MAHDI JABER; AL ANI AWATEF A IBRAHIM; SHAHEED DHURGHAM QASIM 摘要:The synthesis of novel conjugate of ibuprofen with the 6-methyl-N1-(4-(pyridin-3-yl) pyrimidin-2-yl) benzene-1,3-diamine derivative showed a potential antiproliferative activity against both colon cancer and breast cancer cell lines. The chemical structure was characterized and confirmed by spectral (FTIR,1H-NMR and 13C NMR), and the Differential Scanning Colorimetry (DSC) Thermal analyzer. While the biological activity was estimated by Genetic Optimization of Ligand Docking (GOLD) software supplied by Cambridge Crystallographic Data Centre (CCDC) and conducted in vitro with the MTT and the calculation of the IC50. The docking process was successfully performed and the chemical synthesis yield was reasonably high. The spectral interpretations show characteristic identification of the target chemical compound. The results indicated a powerful antitumor drug against breast cancer (MCF7) and colon (HCT116) cell lines. On the other hand, to evaluate the toxicity profile, the Madin-Darby Canine Kidney (MDCK) normal (noncancerous) cell line, was utilized.
1: Moore RA, Derry S, Wiffen PJ, Straube S, Aldington DJ. Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions. Eur J Pain. 2015 Oct;19(9):1213-23. doi: 10.1002/ejp.649. Epub 2014 Dec 22. Review. doi: 10.1002/14651858.CD011509.pub2. Review. doi: 10.1002/14651858.CD003481.pub6. Review. doi: 10.4097/kjae.2015.68.1.3. Epub 2015 Jan 28. Review. 5: Kelly LE, Sommer DD, Ramakrishna J, Hoffbauer S, Arbab-Tafti S, Reid D, Maclean J, Koren G. Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial. Pediatrics. 2015 Feb;135(2):307-13. doi: 10.1542/peds.2014-1906. doi: 10.1002/14651858.CD010107.pub3. Review. doi: 10.1002/ebch.1978. Review. doi: 10.1517/14740338.2014.846324. Epub 2013 Nov 21. Review. Review. doi: 10.1016/j.pain.2013.08.013. Epub 2013 Aug 19. Review. doi: 10.2147/CPAA.S59376. eCollection 2014. Review. 12: Bailey E, Worthington HV, van Wijk A, Yates JM, Coulthard P, Afzal Z. Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth. Cochrane Database Syst Rev. 2013 Dec 12;12:CD004624. doi: 10.1002/14651858.CD004624.pub2. Review. doi: 10.1016/j.ijpharm.2013.09.019. Epub 2013 Sep 21. Review. doi: 10.1002/14651858.CD007550.pub3. Review. doi: 10.1002/14651858.CD009572.pub2. Review. doi: 10.1007/s40261-013-0113-x. Review. Epub 2013 May 17. Review. Review. doi: 10.1002/14651858.CD010210.pub2. Review. doi: 10.1002/14651858.CD010289.pub2. Review.
合成参考文献
参考文献:10.1007/s00296-010-1365-x 摘要:Bloom BJ, Alario AJ, Miller LC. Intra-articular corticosteroid therapy for juvenile idiopathic arthritis: report of an experiential cohort and literature review. Rheumatology International. 2010 Feb 14;31(6):749–56. doi: 10.1007/s00296-010-1365-x. 参考文献:10.2165/11532890-000000000-00000 摘要:Leroy S, Marc E, Bavoux F, Tréluyer JM, Gendrel D, Bréart G, Pons G, Chalumeau M. Hospitalization for severe bacterial infections in children after exposure to NSAIDs: a prospective adverse drug reaction reporting study. Clin Drug Investig. 2010;30(3):179–85. doi: 10.2165/11532890-000000000-00000. 参考文献:10.1186/ar2909 摘要:Christensen R, Bliddal H. Is Phytalgic®a goldmine for osteoarthritis patients or is there something fishy about this nutraceutical A summary of findings and risk-of-bias assessment. Arthritis Research & Therapy. 2010 Feb 08;12(1):105. doi: 10.1186/ar2909. 参考文献:10.18632/aging.100021 摘要:Choi SH, Bosetti F. Cyclooxygenase-1 null mice show reduced neuroinflammation in response to beta-amyloid. Aging (Albany NY). 2009 Feb 11;1(2):234–44. 参考文献:10.18632/aging.100039 摘要:Candelario-Jalil E. A role for cyclooxygenase-1 in beta-amyloid-induced neuroinflammation. Aging (Albany NY). 2009 Apr 13;1(4):350–3.