专利号:US-2012177593-A1 优先权日:2009-07-20 标 题 :Synthesis of dendrimer conjugates 发明人:BAKER JR JAMES R; ZHANG YUEHUA; THOMAS THOMMEY P; DESAI ANKUR MAHESH 权利人:BAKER JR JAMES R; ZHANG YUEHUA; THOMAS THOMMEY P; DESAI ANKUR MAHESH; UNIV MICHIGAN 摘要:The present invention relates to novel methods of synthesis of therapeutic and diagnostic dendrimers. In particular, the present invention is directed to novel dendrimer conjugates, novel methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer, inflammatory disease) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer conjugates of the present invention may further comprise at least two different components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy. Furthermore, the novel synthesis methods of certain embodiments of the present invention provide significant advantages with regard to total reaction time and simplicity.
专利号:US-12391691-B2 优先权日:2018-11-16 标题:Synthesis of key intermediate of KRAS G12C inhibitor compound 发明人:PARSONS ANDREW THOMAS; COCHRAN BRIAN MCNEIL; POWAZINIK IV WILLIAM; CAPORINI MARC ANTHONY 权利人:AMGEN INC 摘要:The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure n nuseful for the synthesis of compounds that target KRAS G12C mutations, such as
专利号:US-2025206736-A1 优先权日:2019-11-14 标题 :Synthesis of kras g12c inhibitor compound 发明人:CORBETT MICHAEL THOMAS; CAILLE SEBASTIEN 权利人:AMGEN INC 摘要:The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2-isopropyl-4-methylpyridin-3-amine, useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.
专利号:US-5886190-A 优先权日:1993-10-04 标 题:Rapid synthesis and use of 18F-fluoromisonidazole and analogs 发明人:WALLACE SIDNEY; YANG DAVID J; CHERIF ABDALLAH 摘要:The present invention involves a rapid synthesis of 18F-FMISO and analogs thereof. New precursors such as 1-(2'-nitro-1'-imidazolyl)-2-0-acetyl-3-0-tosylpropanol, glycerol-1,3-ditosylate-2-0-acetylate, 1-(2'-nitro-1'-imidazolyl)-2,3-0-diacetyl-4-0-tosylbutanol and threitol 1,4-di-tosylate-2,3-0-diacetylate, are also important aspects of the invention. A further aspect of the invention is the development of a hydrophilic PET ligand to image tumor hypoxia. Erythrotosyl analogue of 2-nitroimidazone (Ts-ETNIM) was prepared from a mixture of 2-nitromidazole, ditosylthreitol and cesium carbonate at 60 DEG C. for 1 hr. Ts-ETNIM was isolated at 70% yield. [18F]fluoroerythronitroimidazole (FETNIM) was then prepared from Ts-ETNIM and K18F/kryptofix TM . The yield for [18F]FETNIM was 26-30% (60 min, decay corrected). Results of biodistribution and PET studies indicate that [18F]FETNIM has the potential to detect tumor hypoxia and is indicated to be less neurotoxic.
专利号:US-8734846-B2 优先权日:2008-06-16 标 题 :Methods for the preparation of targeting agent functionalized diblock copolymers for use in fabrication of therapeutic targeted nanoparticles 发明人:ALI MIR M; HRKACH JEFF; ZALE STEPHEN E; ALVAREZ DE CIENFUEGOS LUIS 权利人:BIND BIOSCIENCES INC 摘要:This application provides nanoparticles and methods of making nanoparticles using pre-functionalized poly(ethylene glycol)(also referred to as PEG) as a macroinitiator for the synthesis of diblock copolymers. Ring opening polymerization yields the desired poly(ester)-poly (ethylene glycol)-targeting agent polymer that is used to impart targeting capability to therapeutic nanoparticles. This “polymerization fromâ€? approach typically employs precursors of the targeting agent wherein the reactivity of functional groups of the targeting agent is masked using protecting groups. Also described is a “coupling toâ€? that utilized the poly(ethylene glycol)-targeting agent conjugate where the targeting agent remains in its native un-protected form. This method uses “orthogonalâ€? chemistry that exhibit no cross reactivity towards functional groups typically found within targeting agents of interest.
专利号:US-2013035307-A1 优先权日:2010-01-26 标 题:Methods for treating or preventing the spread of cancer using semi-synthetic glycosaminoglycosan ethers 发明人:PRESTWICH GLENN D; KENNEDY THOMAS P 权利人:UNIV UTAH RES FOUND; PRESTWICH GLENN D; KENNEDY THOMAS P 摘要:Described herein are methods for the treatment and prevention of tumor metastasis using alkylated and fluoroalkylated semi-synthetic glycosaminoglycan ethers (“SAGEsâ€?). The synthesis of sulfated alkylated and fluoroalkylated SAGEs is also described.
1: Hurwitz SJ, Coleman CN, Riese N, Loeffler JS, Alexander E 3rd, Buswell L, Neben TY, Shargel L, Kramer RA. Distribution of etanidazole into human brain tumors: implications for treating high grade gliomas. Int J Radiat Oncol Biol Phys. 1992;22(3):573-6. doi: 10.1016/0360-3016(92)90879-m. 52(2):208-14. doi: 10.1269/jrr.10122. 20(4):723-31. doi: 10.1016/0360-3016(91)90015-v. 28(25):3724-30. doi: 10.1016/j.biomaterials.2007.04.032. Epub 2007 May 3. 29(3):545-8. doi: 10.1016/0360-3016(94)90453-7. 20(4):703-8. doi: 10.1016/0360-3016(91)90012-s. 81(3):263-80. doi: 10.1016/s0168-3659(02)00066-4. 55(5):1182-5. doi: 10.1016/s0360-3016(02)04391-2. 20(5):987-95. doi: 10.1016/0360-3016(91)90195-a. 78(4):267-74. doi: 10.1080/09553000110105695. 103(3):599-607. doi: 10.1016/j.jconrel.2004.12.012. 29(3):541-3. doi: 10.1016/0360-3016(94)90452-9. 14(2):157-83. doi: 10.1163/156856203321142597. 58:45-63. doi: 10.1007/978-1-4615-3876-9_3. 91(5):895-7. doi: 10.1016/j.ijrobp.2015.01.041. 92(1093):20170966. doi: 10.1259/bjr.20170966. Epub 2018 Jul 6. 17: Eschwège F, Sancho-Garnier H, Chassagne D, Brisgand D, Guerra M, Malaise EP, Bey P, Busutti L, Cionini L, N'Guyen T, Romanini A, Chavaudra J, Hill C. Results of a European randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas. Int J Radiat Oncol Biol Phys. 1997 Sep 1;39(2):275-81. doi: 10.1016/s0360-3016(97)00327-1. 29(3):535-40. doi: 10.1016/0360-3016(94)90451-0. 11(4):489-99. doi: 10.3109/02656739509022484. 81(12):929-34. doi: 10.1093/jnci/81.12.929.
合成参考文献
参考文献:10.1007/s10439-011-0349-7 摘要:Pishko GL, Astary GW, Mareci TH, Sarntinoranont M. Sensitivity Analysis of an Image-Based Solid Tumor Computational Model with Heterogeneous Vasculature and Porosity. Annals of Biomedical Engineering. 2011 Jul 13;39(9):2360. doi: 10.1007/s10439-011-0349-7.