- Organozirconium chemistry on cyclosporin: A novel process for the highly stereoselective synthesis of (E)-ISA247 (voclosporin) and close analogues
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Application of organozirconium chemistry to cyclosporin has led to the development of a novel process for the highly stereoselective synthesis of the E-isomer of ISA247 (voclosporin), which is a potent immunosuppressive agent currently in late stage human clinical trials for treatment of psoriasis, prevention of kidney transplant rejection, and ophthalmic indications. Synthesis of deuterated analogues of ISA247 and a cyclosporin triene analogue using the same methodology is also described. Georg Thieme Verlag Stuttgart. New York.
- Maeng, Jun-Ho,Yang, Zhicai,Manning, David D.,Masih, Liaqat,Cao, Yeyu,Pattamana, Kevin G.,Bois, Frederic,Molino, Bruce F.
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- Anti-inflammatory effects of extracellular cyclosporins are exclusively mediated by CD147
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Leukocyte trafficking and recruitment is a critical process in host immune surveillance and in inflammatory diseases. Extracellular cyclophilins (eCyps) have been identified as a novel class of chemotactic mediators. The impact of eCyp/CD147 interactions for the recruitment of leukocytes during inflammation was analyzed using a structurally simplified cell-impermeable eCyp inhibitor. This compound was highly effective at inhibiting leukocyte migration toward CypA in vitro as well as in the recruitment of leukocytes during inflammation in a mouse model of experimentally induced peritonitis and delayed-type hypersensitivity reaction. By using CD147-/- mice in combination with the cell-impermeable eCyp inhibitor, we were able to show that the action of eCyps in inflammation is exclusively mediated by interaction with CD147. Our findings suggest that blocking eCyps may be an effective therapeutic target for reducing inflammatory diseases associated with leukocyte recruitment.
- Malesevic, Miroslav,Gutknecht, Danny,Prell, Erik,Klein, Claudia,Schumann, Michael,Nowak, Romana A.,Simon, Jan C.,Schiene-Fischer, Cordelia,Saalbach, Anja
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- NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF
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A compound of the Formula (I) is disclosed: (I) or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kindey diseases, and hair loss using the same.
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- Cyclosporin derivatives
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The present invention relates to novel cyclosporin derivatives that do not cross the cellular membrane. The compounds according to the invention are used in medicine, more particularly in the treatment/diagnosis of acute and chronic inflammatory diseases,
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Page/Page column 71
(2016/10/17)
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- Chemical tagging of a drug target using 5-sulfonyl tetrazole
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Irreversible modification is one of the most promising strategies to identify cellular receptors of bioactive small molecules. Here we report that receptor proteins can be chemically tagged using a 5-sulfonyl tetrazole probe. 5-Sulfonyl tetrazole easily a
- Otsuki, Satsuki,Nishimura, Shinichi,Takabatake, Hisae,Nakajima, Kozue,Takasu, Yasuaki,Yagura, Toru,Sakai, Yuki,Hattori, Akira,Kakeya, Hideaki
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p. 1608 - 1611
(2013/04/10)
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- Cyclosporin Derivatives
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A cyclosporin derivative of general Formula (I) or a pharmaceutically compatible salt thereof, which have a pharmaceutical effectiveness, for example in the case of chronic inflammatory diseases. The cyclosporin derivatives are preferably free from a peptide section capable of passing through the membrane of a biological cell.
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Page/Page column 16
(2012/08/08)
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- Use of cyclosporin alkene analogues for preventing or treating viral-induced disorders
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The present invention relates to methods of preventing or treating a mammal with a viral-induced disorder. The method involves administering to the mammal a therapeutically effective amount of a compound represented by Formula I, as shown below: or a phar
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Page/Page column 15-16
(2008/06/13)
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- Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders
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The present invention relates to methods of preventing or treating a mammal with a viral-induced disorder. The method involves administering to the mammal a therapeutically effective amount of a compound represented by Formnula I, as shown below: or a pharmaceutically acceptable salt thereof, with X, R0, and R1 defined herein, under conditions effective to prevent or treat the viral-induced disorder.
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Page/Page column 7; 13
(2010/11/28)
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- Use of cyclosporin alkyne/alkene analogues for preventing or treating viral-induced disorders
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The present invention relates to methods of preventing or treating a mammal with a viral-induced disorder. The method involves administering to the mammal a therapeutically effective amount of a compound represented by Formula I, as shown below: or a phar
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Page/Page column 11
(2010/11/28)
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- Novel cyclosporin alkynes and their utility as pharmaceutical agents
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The compounds of the present invention are represented by the chemical structure found in Formula I: or a pharmaceutically acceptable salt thereof, with X, R0, and R1 defined herein.
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Page/Page column 11
(2008/06/13)
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- Novel cyclosporin analogues and their pharmaceutical uses
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The compounds of the present invention are represented by Formula I, as shown below: or a pharmaceutically acceptable salt thereof, with X, R0, R1, and R2 defined herein.
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Page/Page column 14
(2008/06/13)
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- Cyclosporin derivatives for the treatment of immune disorders
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The present invention relates to a cyclosporin analog of the following formula (I) or a pro-drug or pharmaceutically acceptable salt thereof: wherein A is of the formula: where Q, W, X, Y, and Z are defined herein. In a second embodiment, the present inve
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Page/Page column 22
(2008/06/13)
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