- Total synthesis of (±) mutisianthol and (±) epi-mutisianthol via intramolecular oxidative Heck cyclization approach Dedicated to the late Professor M. G. Kulkarni, Department of Chemistry, SPPU, Pune for his pioneering work in the field of Wittig olefinat
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A simple and straight forward synthesis of (±) mutisianthol and its epimer is described. Implementation of 4-pentenal derivative for palladium catalyzed intramolecular 5-endo-trig Heck cyclization is effective. Other key steps involved are Wittig olefinat
- Bhorkade, Shashikant B.,Gavhane, Kishor B.,Shinde, Vaishali S.
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Read Online
- Anti-AIDS agents 33.1 Synthesis and anti-HIV activity of mono-methyl substituted 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogues
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Four isomeric methyl substituted DCK analogues (2-5) were asymmetrically synthesized from different starting materials. 3-Methyl, 4-methyl, and 5- methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (2 -4) all were extremely potent against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of -7 μM and >3.72 x 108, respectively, which are much better than those of DCK and AZT in this assay.
- Xie, Lan,Takeuchi, Yasuo,Cosentino, L. Mark,Lee, Kuo-Hsiung
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Read Online
- HETEROCYCLIC IMMUNOMODULATORS AS PDL1 CHECKPOINT INHIBITOR
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The disclosure describes pyridinone-containing inhibitors of PD-L1, pharmaceutical compositions comprising these compounds, chemical processes for preparing these compounds, and their use in the treatment of infectious diseases and cancer. Formula (I).
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(2020/12/29)
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- COMBINATION OF HEPATITIS B VIRUS (HBV) VACCINES AND PD-L1 INHIBITORS
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Therapeutic combinations of hepatitis B virus (HBV) vaccines and PD-L1 inhibitors are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the dis
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Page/Page column 87-89
(2021/01/22)
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- UREA COMPOUND AND PREPARATION METHOD AND APPLICATION THEREOF
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The present invention relates to a urea compound and a preparation method and an application thereof. The structure of the present compound is represented by formula (I), the definition of each variable in the formula being as described in the description. The compound can block interaction between the PD-1/PD-L1 signalling pathways. The compound of the present invention can be used for treating or preventing diseases related to the signalling pathways, such as cancer, autoimmune disease, chronic infectious disease, and other diseases.
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Paragraph 0068; 0069
(2019/11/14)
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- Development of noviomimetics that modulate molecular chaperones and manifest neuroprotective effects
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Heat shock protein 90 (Hsp90) is a chaperone under investigation for the treatment of cancer and neurodegenerative diseases. Neuroprotective Hsp90 C-terminal inhibitors derived from novobiocin (novologues) include KU-32 and KU-596. These novologues modulate molecular chaperones and result in an induction of Heat Shock Protein 70 (Hsp70). “Noviomimetics” replace the synthetically complex noviose sugar with a simple cyclohexyl moiety to maintain biological efficacy as compared to novologues KU-596 and KU-32. In this study, we further explore the development of noviomimetics and evaluate their efficacy using a luciferase refolding assay, immunoblot analysis, a c-jun assay, and an assay measuring mitochondrial bioenergetics. These new noviomimetics were designed and synthesized and found to induce Hsp70 and improve biological activity. Noviomimetics 39e and 40a were found to induce Hsp70 and exhibit promising effects in cellular assays.
- Forsberg, Leah K.,Anyika, Mercy,You, Zhenyuan,Emery, Sean,McMullen, Mason,Dobrowsky, Rick T.,Blagg, Brian S.J.
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supporting information
p. 1428 - 1435
(2017/11/17)
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- Modified biphenyl Hsp90 C-terminal inhibitors for the treatment of cancer
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Heat Shock Protein 90 (Hsp90) is a molecular chaperone under clinical investigation for the treatment of neurodegenerative diseases and cancer. Neuroprotective Hsp90 C-terminal inhibitors (novologues) contain a biaryl ring system, and include KU-596, which was modified and investigated for potential anti-cancer activity. Incorporation of a benzamide group onto the biaryl novologues in lieu of the acetamide yielded compounds that manifest anti-cancer activity. Further exploration of the central phenyl ring led to compounds with enhanced anti-proliferative activity. The design, synthesis, and evaluation of these new analogs against breast and prostate cancer cell lines is reported herein, where it was found that 8b and 10 manifest potent anti-proliferative activity and a robust degradation of Hsp90 client-dependent proteins.
- Forsberg, Leah K.,Liu, Weiya,Holzbeierlein, Jeffrey,Blagg, Brian S.J.
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p. 4514 - 4519
(2017/09/12)
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- 1 -HYDROXY-BENZOOXABOROLES AS ANTIPARASITIC AGENTS
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Provided are compounds useful for controlling endoparasites both in animals and agriculture. Further provided are methods for controlling endoparasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling endoparasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. The claimed compounds are described by the following Markush formula:A typical example for a compound according to above formula is: A typical example for a compound according to above formula is:
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Page/Page column 135
(2014/10/03)
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- Anti-AIDS agents. 37. Synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents
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To explore the structural requirements of (+)-cis-khellactone derivatives as novel anti-HIV agents, 24 monosubstituted 3',4'-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK) derivatives were synthesized asymmetrically. These compounds included 4 isomeric monomethoxy analogues (3- 6), 4 isomeric monomethyl analogues (7-10), 4 4-alkyl/aryl-substituted analogues (11-14), and 12 4-methyl-(+)-cis-khellactone derivatives (15-26) with varying 3',4'-substituents. These (+)-cis-khellactone derivatives were screened against HIV-1 replication in acutely infected H9 lymphocytes. The results demonstrated that the (3'R,4'R)-(+)-cis-khellactone skeleton, two (S)-(-)-camphanoyl groups at the 3'- and 4'-positions, and a methyl group on the coumarin ring, except at the 6-position, were optimal structural moieties for anti-HIV activity. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'- di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khellactone showed EC50 and therapeutic index values of -5 μM and >2.15 x 106, respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Furthermore, 8 and 9 also showed potent inhibitory activity against HIV-1 replication in the CEM-SS cell line, and most monosubstituted DCK analogues were less toxic than DCK in both assays.
- Xie, Lan,Takeuchi, Yasuo,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2662 - 2672
(2007/10/03)
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