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-9447149-B2 优先权日:2012-03-06 标 题 :Methods and compositions for the rapid synthesis of radiometal-labeled probes 发明人:CHEN KAI; CONTI PETER STEPHEN 权利人:UNIV SOUTHERN CALIFORNIA 摘要:The present application is directed to rapid and efficient synthesis of radiometal-labeled probes, pharmaceutical compositions comprising radiometal-labeled probes, and methods of using the radiometal-labeled probes. Such radiometal-labeled probes can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT), and therapy studies.
专利号:US-9096647-B2 优先权日:2008-09-16 标题 :Simplified one-pot synthesis of [18F]SFB for radiolabeling 发明人:OLMA SEBASTIAN; SHEN CLIFTON KWANG-FU 权利人:UNIV CALIFORNIA 摘要:A non-aqueous single pot synthesis of [ 18 F]SFB is set forth. The [ 18 F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.
专利号:US-2004101523-A1 优先权日:1989-07-27 标题:Renal-selective prodrugs for control of renal smpathetic nerve activity in the treatment of hypertension 发明人:REITZ DAVID B; KOEPKE JOHN P; BLAINE EDWARD H; SCHUH JOSEPH R; MANNING ROBERT E; SMITS GLENN J 权利人:SEARLE & CO 摘要:Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-β-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-β-hydroxylase inhibitors, of which N-acetyl-γ-glutamyl fusaric acid hydrazide (shown below) is preferred.
专利号:WO-9201667-A1 优先权日:1990-07-25 标题 :Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension 发明人:REITZ DAVID B; KOEPKE JOHN P; BLAINE EDWARD H; SCHUH JOSEPH R; MANNING ROBERT E; SMITS GLENN J 权利人:SEARLE & CO 摘要:Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-β-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kydney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-β-hydroxylase-inhibitors, of which N-acetyl-η-glutamyl fusaric acid hydrazide [represented in formula (a)] is preferred.
专利号:US-9388147-B2 优先权日:2009-11-13 标题 :Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis 发明人:MARTINBOROUGH ESTHER; BOEHM MARCUS F; YEAGER ADAM RICHARD; TAMIYA JUNKO; HUANG LIMING; BRAHMACHARY ENUGURTHI; MOORJANI MANISHA; TIMONY GREGG ALAN; BROOKS JENNIFER L; PEACH ROBERT; SCOTT FIONA LORRAINE; HANSON MICHAEL ALLEN 权利人:RECEPTOS INC; CELGENE INTERNAT II SÃ?RL 摘要:Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.
1: Olutoye OA, Sheikh F, Zamora IJ, Yu L, Akinkuotu AC, Adesina AM, Olutoye OO. Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain. Am J Obstet Gynecol. 2016 Apr;214(4):542.e1-8. doi: 10.1016/j.ajog.2015.10.927. Epub 2015 Nov 4. doi: 10.1097/ALN.0000000000001017. doi: 10.1016/j.neulet.2015.11.037. Epub 2015 Nov 26. doi: 10.1213/ANE.0000000000001111. 5: Johansen SL, Iceman KE, Iceman CR, Taylor BE, Harris MB. Isoflurane causes concentration-dependent inhibition of medullary raphé 5-HT neurons in situ. Auton Neurosci. 2015 Dec;193:51-6. doi: 10.1016/j.autneu.2015.07.002. Epub 2015 Jul 17. 6: Cheng B, Zhang Y, Wang A, Dong Y, Xie Z. Vitamin C Attenuates Isoflurane-Induced Caspase-3 Activation and Cognitive Impairment. Mol Neurobiol. 2015 Dec;52(3):1580-9. doi: 10.1007/s12035-014-8959-3. Epub 2014 Nov 4.
合成参考文献
参考文献:10.1007/s00259-009-1370-z 摘要:Nayak TK, Regino CAS, Wong KJ, Milenic DE, Garmestani K, Baidoo KE, Szajek LP, Brechbiel MW. PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A″-DTPA-cetuximab. European Journal of Nuclear Medicine and Molecular Imaging. 2010 Feb 13;37(7):1368–76. doi: 10.1007/s00259-009-1370-z. 参考文献:10.1007/s11748-009-0529-7 摘要:Safaii N, Kazemi B. Effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery. General Thoracic and Cardiovascular Surgery. 2010 Feb 13;58(2):62–7. doi: 10.1007/s11748-009-0529-7. 参考文献:10.1007/s00423-010-0601-x 摘要:Binnebösel M, Ricken C, Klink CD, Junge K, Jansen M, Schumpelick V, Lynen Jansen P. Impact of gentamicin-supplemented polyvinylidenfluoride mesh materials on MMP-2 expression and tissue integration in a transgenic mice model. Langenbecks Arch Surg. 2010 Apr;395(4):413–20. doi: 10.1007/s00423-010-0601-x. 参考文献:10.1097/01.mlg.0000180173.81034.4d 摘要:Kim JU, Lee HJ, Kang HH, Shin JW, Ku SW, Ahn JH, Kim YJ, Chung JW. Protective effect of isoflurane anesthesia on noise-induced hearing loss in mice. Laryngoscope. 2005 Nov;115(11):1996–9. doi: 10.1097/01.mlg.0000180173.81034.4d. 参考文献:10.1016/j.joms.2008.12.012 摘要:Rossi A, Falzetti G, Donati A, Orsetti G, Pelaia P. Desflurane Versus Sevoflurane to Reduce Blood Loss in Maxillofacial Surgery. Journal of Oral and Maxillofacial Surgery. 2010 May;68(5):1007–12. doi: 10.1016/j.joms.2008.12.012.