专利号:US-10925977-B2 优先权日:2006-10-05 标 题 :Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications 发明人:YANG DAVID J; YU DONGFANG; THOMPSON ANDREW S 权利人:YANG DAVID J; YU DONGFANG; THOMPSON ANDREW S; CEIL POINT LLC; UNIV TEXAS 摘要:Novel methods of synthesis of chelator-targeting ligand conjugates, compositions comprising such conjugates, and therapeutic and diagnostic applications of such conjugates are disclosed. The compositions include chelator-targeting ligand conjugates optionally chelated to one or more metal ions. Methods of synthesizing these compositions in high purity are also presented. Also disclosed are methods of imaging, treating and diagnosing disease in a subject using these novel compositions, such as methods of imaging a tumor within a subject and methods of diagnosing myocardial ischemia.
专利号:US-9085544-B2 优先权日:2010-08-18 标 题 :Method of synthesis of substituted hexitols such as dianhydrogalactitol 发明人:BROWN DENNIS M; LI MIKE TSO-PING 权利人:DEL MAR PHARMACEUTICALS 摘要:The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80° C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol. Another method produces dianhydrogalactitol from dulcitol; this method comprises: (1) reacting dulcitol with a reactant to convert the 1,6-hydroxy groups of dulcitol to an effective leaving group to generate an intermediate; and (2) reacting the intermediate with an inorganic weak base to produce dianhydrogalactitol through an intramolecular S N 2 reaction. Other methods for the synthesis of dianhydrogalactitol from dulcitol are described.
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-9630938-B2 优先权日:2010-08-18 标 题 :Method of synthesis of substituted hexitols such as dianhydrogalactitol 发明人:BROWN DENNIS M; LI MIKE TSO-PING 权利人:DELMAR PHARMACEUTICALS INC 摘要:The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80° C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol. Another method produces dianhydrogalactitol from dulcitol; this method comprises: (1) reacting dulcitol with a reactant to convert the 1,6-hydroxy groups of dulcitol to an effective leaving group to generate an intermediate; and (2) reacting the intermediate with an inorganic weak base to produce dianhydrogalactitol through an intramolecular S N 2 reaction. Other methods for the synthesis of dianhydrogalactitol from dulcitol are described.
专利号:US-8921585-B2 优先权日:2010-08-18 标题 :Method of synthesis of substituted hexitols such as dianhydrogalactitol 发明人:BROWN DENNIS M 权利人:DEL MAR PHARMACEUTICALS 摘要:The present invention provides an efficient method of synthesizing and purifying dianhydrohexitols such as dianhydrogalactitol. In general, as applied to dianhydrogalactitol, the method comprises: (1) reacting dulcitol with a concentrated solution of hydrobromic acid at a temperature of about 80° C. to produce dibromogalactitol; (2) reacting the dibromogalactitol with potassium carbonate in t-butanol to produce dianhydrogalactitol; and (3) purifying the dianhydrogalactitol using a slurry of ethyl ether to produce purified dianhydrogalactitol. Another method produces dianhydrogalactitol from dulcitol; this method comprises: (1) reacting dulcitol with a reactant to convert the 1,6-hydroxy groups of dulcitol to an effective leaving group to generate an intermediate; and (2) reacting the intermediate with an inorganic weak base to produce dianhydrogalactitol through an intramolecular S N 2 reaction. Other methods for the synthesis of dianhydrogalactitol from dulcitol are described.
1: Jeney A, Kralovánszky J, Lapis K. [Anticancer drug research in Hungary, 1950-2000]. Magy Onkol. 2017 Dec 18;61(4):375-382. Epub 2017 Nov 30. Hungarian. doi: 10.18632/oncotarget.10763. 3: Ishiyama T, Jinguu A, Matsumoto H, Kikuchi J, Suzuki T, Yamakawa M. [A case of adult primitive neuroectodermal tumor(PNET)with multiple lung metastases effectively treated with ADM, IFM(AI)regimen]. Gan To Kagaku Ryoho. 2012 Aug;39(8):1287-9. Japanese. doi: 10.1007/s10555-010-9259-7. Review. doi: 10.1007/s11060-010-0151-7. Epub 2010 Mar 11. 6: Song X, Wang JB, Yin DL, Yang HY, Liu LX, Jiang HC. Down-regulation of lung resistance related protein by RNA interference targeting survivin induces the reversal of chemoresistances in hepatocellular carcinoma. Chin Med J (Engl). 2009 Nov 5;122(21):2636-42. doi: 10.1007/s12253-009-9208-3. Epub 2009 Sep 12. doi: 10.1016/j.pnpbp.2009.03.018. Epub 2009 Mar 28. Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882). Eur J Cancer. 2008 Jun;44(9):1210-6. doi: 10.1016/j.ejca.2007.12.005. Epub 2008 Jan 14. Chinese. Review. Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421. Blood. 2006 Feb 15;107(4):1315-24. Epub 2005 Oct 27.
合成参考文献
摘要:Cancer Chemotherapy Reports, Part 1., 56(593), 1972 [] 摘要:National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program., JAN1986 摘要:Antibiotics and Chemotherapy, 23(50), 1978 [] 参考文献:10.1007/bf00177442 摘要:Sioutos PJ, Hamilton AJ, Narotam PK, Weinand ME. Unusual early recurrence of a cerebellar pilocytic astrocytoma following complete surgical resection. Case report and review of the literature. J Neurooncol. 1996 Oct;30(1):47–54. doi: 10.1007/bf00177442. 参考文献:10.1023/a:1006118800753 摘要:Kuratsu J, Arita N, Kurisu K, Uozumi T, Hayakawa T, Ushio Y. A phase II study of KRN8602(MX2), a novel morpholino anthracycline derivative, in patients with recurrent malignant glioma. J Neurooncol. 1999 Apr;42(2):177–81. doi: 10.1023/a:1006118800753.