- Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**
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A complementary dual carbonyl activation strategy for the synthesis of polycyclic alkaloids has been developed. Successful applications include the synthesis of tetracyclic alkaloids harmalanine and harmalacinine, pentacyclic indoloquinolizidine alkaloid nortetoyobyrine, and octacyclic β-carboline alkaloid peganumine A. The latter synthesis features a protecting-group-free assembly and an asymmetric disulfonimide-catalyzed cyclization. Furthermore, formal syntheses of hirsutine, deplancheine, 10-desbromoarborescidine A, and oxindole alkaloids rhynchophylline and isorhynchophylline have been achieved. Finally, a concise synthesis of berberine alkaloid ilicifoline B was completed.
- Christmann, Mathias,He, Guoli,List, Benjamin
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supporting information
p. 13591 - 13596
(2021/05/07)
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- Design, synthesis, and biological evaluation of HDAC degraders with CRBN E3 ligase ligands
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Histone deacetylases (HDACs) play important roles in cell growth, cell differentiation, cell apoptosis, and many other cellular processes. The inhibition of different classes of HDACs has been shown to be closely related to the therapy of cancers and other diseases. In this study, a series of novel CRBN-recruiting HDAC PROTACs were designed and synthesized by linking hydroxamic acid and benzamide with lenalidomide, pomalidomide, and CC-220 through linkers of different lengths and types. One of these PROTACs, denoted 21a, with a new benzyl alcohol linker, exhibited comparably excellent HDAC inhibition activity on different HDAC classes, acceptable degradative activity, and even better in vitro anti-proliferative activities on the MM.1S cell line compared with SAHA. Moreover, we report for the first time the benzyl alcohol linker, which could also offer the potential to be used to develop more types of potent PROTACs for targeting more proteins of interest (POI).
- Li, Jia,Lu, Wei,Lu, Yingxin,Shao, Yingying,Su, Mingbo,Sun, Danwen,Xiao, Donghuai,Zhou, Yubo,Zhu, Shulei
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- LIPID PRODRUGS OF PREGNANE NEUROSTEROIDS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00295; 00296
(2020/02/23)
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- LIPID PRODRUGS OF JAK INHIBITORS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00414-00415
(2020/09/12)
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- LIPID PRODRUGS OF BTK INHIBITORS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00405; 00423; 00424
(2020/09/12)
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- LIPID PRODRUGS OF GLUCOCORTICOIDS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00407; 00408
(2020/09/12)
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- LYMPHATIC SYSTEM-DIRECTING LIPID PRODRUGS
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a provided lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00430; 00431
(2019/03/17)
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- COMPOUNDS AND COMPOSITIONS FOR DELIVERING ACTIVE AGENTS
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Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are provided as well.
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Page/Page column 77; 82
(2010/02/14)
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- Dispiro-1,2,4-trioxolanes by Ozonolysis of Cycloalkylidenecycloalkanes on Polyethylene
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Ozonolyses of symmetrical (1b-d) and of unsymmetrical cycloalkylidenecycloalkanes (8a, b) afforded the dispiro-1,2,4-trioxolanes 4b-d and 9a, b, respectively.Their thermal decompositions gave mixtures of the cyclic ketones (3) and lactones (6).Photolysis afforded in addition to 3 and 6 the cyclic anhydrides 13, which are isomeric with the corresponding disoiro-1,2,4-trioxolanes.
- Griesbaum, Karl,Krieger-Beck, Petra,Beck, Johannes
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p. 391 - 396
(2007/10/02)
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