475160-83-9Relevant articles and documents
Near-Infrared Fluorescent Molecular Probe for Sensitive Imaging of Keloid
Miao, Qingqing,Yeo, David C.,Wiraja, Christian,Zhang, Jianjian,Ning, Xiaoyu,Xu, Chenjie,Pu, Kanyi
, p. 1256 - 1260 (2018)
Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloi
Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
supporting information, p. 4567 - 4587 (2021/05/06)
The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
DIRECTED CONJUGATION TECHNOLOGIES
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Paragraph 0989; 0990, (2021/05/29)
Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.
NEAR INFRA-RED MOLECULAR PROBES FOR USE IN DIAGNOSIS OF FIBROTIC CONDITIONS AND SCREENING OF ANTI-FIBROTIC DRUGS
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Page/Page column 39; 40, (2019/07/19)
We disclose a compound of formula I: [X]n-[Y]m-Z where X represents a fluorophore group covalently linked to the rest of the molecule by way of an oxygen atom or an NH group; Y is a self-immolative linking group; Z represents an N-bl
Synthesis and biological characterization of protease-activated prodrugs of doxazolidine
Barthel, Benjamin L.,Rudnicki, Daniel L.,Kirby, Thomas Price,Colvin, Sean M.,Burkhart, David J.,Koch, Tad H.
experimental part, p. 6595 - 6607 (2012/10/07)
Doxazolidine (doxaz) is a new anthracycline anticancer agent. While structurally similar to doxorubicin (dox), doxaz acts via a distinct mechanism to selectively enhance anticancer activity over cardiotoxicity, the most significant clinical impediment to successful anthracycline treatment. Here, we describe the synthesis and characterization of a prodrug platform designed for doxaz release mediated by secreted proteolytic activity, a common association with invasiveness and poor prognosis in cancer patients. GaFK-Doxaz is hydrolyzable by the proteases plasmin and cathepsin B, both strongly linked with cancer progression, as well as trypsin. We demonstrate that activation of GaFK-Doxaz releases highly potent doxaz that powerfully inhibits the growth of a wide variety of cancer cells (average IC50 of 8 nM). GaFK-Doxaz is stable in human plasma and is poorly membrane permeable, thereby limiting activation to locally secreted proteolytic activity and reducing the likelihood of severe side effects.
METHODS OF TREATING CANCER WITH DOXAZOLIDINE AND PRODRUGS THEREOF
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Page/Page column 23, (2010/11/28)
The invention provides therapeutically effective compounds for the prevention and treatment of cancer and pharmaceutical compositions containing these compounds as well as methods of using and administering these compounds. The invention also includes methods of activating a prodrug of these therapeutically effective compounds by the administration of a peptide-directed targeting construct that delivers a prodrug-activating enzyme to a target activation site.
Synthesis of rigid photoswitchable hemithioindigo ω-amino acids
Schadendorf, Torsten,Hoppmann, Christian,Rück-Braun, Karola
, p. 9044 - 9047 (2008/03/18)
The synthesis of novel N-Boc- and N-Fmoc protected hemithioindigo-based ω-amino acids is described. An approach to modulate the thermal stability of a hemithioindigo subunit is presented. Placing the amino-group in the stilbene part from the para- to meta
4-PHENYL-5-OXO-1,4,5,6,7,8-HEXAHYDROQUINOLINE DERIVATIVES THE TREATMENT OF INFERTILITY
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Page/Page column 57, (2010/11/24)
The present invention relates to 4-phenyl-5-oxo-l,4)5,6,7,8-hexahydroquinoline derivatives according to Formula I, Formula I or a pharmaceutically acceptable salt thereof, wherein R1 is (l-6C)alkyl, (2-6C)alkenyl or (2-6C)aDcynyl; R2, R3 are independently halogen, (l-4C)allcyl, (2-4C)alkenyl, (2-4C)- alkynyl, (1 -4C)aBcoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy; R4 is phenyl or (2-5C)- heteroaryl, both substituted with R7 and optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy , (l-4C)alkylthio and (di)(l-4C)- alkylamino. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these 4-phenyl-5-oxo-l, 4,5,6, 7,8-hexahydro- quinoline derivatives in therapy, more specifically for the treatment of infertility
Dioxanes and uses thereof
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, (2008/06/13)
In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel compounds of general formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1, R2, R3, n, X and Y are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier. The present invention further provides compounds capable of inhibiting histone deacetylatase activity and methods for treating disorders regulated by histone deacetylase activity (e.g., cancer and protozoal infections) comprising administering a therapeutically effective amount of a compound of formula (I) to a subject in need thereof. The present invention additionally provides methods for modulating the glucose-sensitive subset of genes downstream of Ure2p. The present invention also provides methods for preparing compounds of the invention.
Dioxanes and uses thereof
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, (2008/06/13)
In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel compounds of general formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1, R2, R3, n, X and Y are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier. The present invention further provides compounds capable of inhibiting histone deacetylatase activity and methods for treating disorders regulated by histone deacetylase activity (e.g., cancer and protozoal infections) comprising administering a therapeutically effective amount of a compound of formula (1) to a subject in need thereof. The present invention additionally provides methods for modulating the glucose-sensitive subset of genes downstream of Ure2p.