129667-70-5Relevant academic research and scientific papers
Development of luciferin analogues bearing an amino group and their application as BRET donors
Takakura, Hideo,Sasakura, Kiyoshi,Ueno, Tasuku,Urano, Yasuteru,Terai, Takuya,Hanaoka, Kenjiro,Tsuboi, Takashi,Nagano, Tetsuo
, p. 2053 - 2061 (2010)
We systematically synthesized bioluminogenic substrates bearing an amino group on benzothiazole, quinoline, naphthalene, and coumarin scaffolds. They emit bioluminescence in various colors: red, orange, yellow, and green. An amino-substituted cou-marylluciferin derivative, coumarylami-noluciferin (CAL), showed the shortest bioluminescence wavelength among substrates reported so far. Further, the fluorescence of CAL did not exhibit solvatochromism, which suggests that its bioluminescence is not susceptible to environmental factors. We applied CAL as an energy-donor substrate for a bioluminescence resonance energy transfer (BRET) system with click beetle red luciferase (CBRluc), a mutant of firefly luciferase, as the energy-donor enzyme and yellow fluorescent protein (YFP) as the energy-acceptor fluorophore, and obtained a clearly bimodal bioluminescence spectrum. Stable bioluminescence that is not influenced by environmental factors is highly desirable for reliable measurements in biological assays.
Nickel-Catalyzed Amination of Aryl Carbamates with Ammonia
Schranck, Johannes,Furer, Patrick,Hartmann, Veronika,Tlili, Anis
, p. 3496 - 3500 (2017)
Aryl carbamates were employed in the nickel-catalyzed monoarylation of ammonia. The applied, well-defined single-component nickel(II) precatalyst contains a Josiphos ligand, is air-stable, and operates without any ancillary reductant. This catalyst system
Structure-based non-nucleoside inhibitor design: Developing inhibitors that are effective against resistant mutants
Smith, Steven J.,Pauly, Gary T.,Hewlett, Katharine,Schneider, Joel P.,Hughes, Stephen H.
, p. 4 - 17 (2021)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit reverse transcription and block the replication of HIV-1. Currently, NNRTIs are usually used as part of a three-drug combination given to patients as antiretroviral therapy. These combinations involve other classes of anti-HIV-1 drugs, commonly nucleoside reverse transcriptase inhibitors (NRTIs). However, attempts are being made to develop two-drug maintenance therapies, some of which involve an NNRTI and an integrase strand transfer inhibitor. This has led to a renewed interest in developing novel NNRTIs, with a major emphasis on designing compounds that can effectively inhibit the known NNRTI-resistant mutants. We have generated and tested novel rilpivirine (RPV) analogs. The new compounds were designed to exploit a small opening in the upper right periphery of the NNRTI-binding pocket. The best of the new compounds, 12, was a more potent inhibitor of the NNRTI-resistant mutants we tested than either doravirine or efavirenz but was inferior to RPV. We describe the limitations on the modifications that can be appended to the “upper right side” of the RPV core and the effects of substituting other cores for the central pyrimidine core of RPV and make suggestions about how this information can be used in NNRTI design.
Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C-O Bond Cleavage
Yue, Huifeng,Guo, Lin,Liu, Xiangqian,Rueping, Magnus
supporting information, p. 1788 - 1791 (2017/04/11)
A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.
Organocatalytic Atroposelective Arylation of 2-Naphthylamines as a Practical Approach to Axially Chiral Biaryl Amino Alcohols
Chen, Ye-Hui,Qi, Liang-Wen,Fang, Fang,Tan, Bin
supporting information, p. 16308 - 16312 (2017/12/04)
The first phosphoric acid catalyzed direct arylation of 2-naphthylamines with iminoquinones for the atroposelective synthesis of axially chiral biaryl amino alcohols has been developed. This reaction constitutes a highly functional-group-tolerant route for the rapid construction of enantioenriched axially chiral biaryl amino alcohols, and is a rare example of 2-naphthylamines acting as nucleophiles in an organocatalytic enantioselective transformation. Furthermore, the products, which feature various halogen atoms, provide access to structurally diverse axially chiral amino alcohols through further transformations.
Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase
Lee, Won-Gil,Frey, Kathleen M.,Gallardo-Macias, Ricardo,Spasov, Krasimir A.,Chan, Albert H.,Anderson, Karen S.,Jorgensen, William L.
, p. 4824 - 4827 (2015/10/28)
Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that incorporate a 7-indolizinylamino or 2-naphthylamino substituent on a pyrimidine or 1,3,5-triazine core. The most potent compounds show below 10 nanomolar activity towards wild-type HIV-1 and variants bearing Tyr181Cys and Lys103Asn/Tyr181Cys resistance mutations. The compounds also feature good aqueous solubility. Crystal structures for two complexes enhance the analysis of the structure-activity data.
Identification of Novel Binding Interactions in the Development of Potent, Selective 2-Naphthamidine Inhibitors of Urokinase. Synthesis, Structural Analysis, and SAR of N-Phenyl Amide 6-Substitution
Wendt, Michael D.,Rockway, Todd W.,Geyer, Andrew,McClellan, William,Weitzberg, Moshe,Zhao, Xumiao,Mantei, Robert,Nienaber, Vicki L.,Stewart, Kent,Klinghofer, Vered,Giranda, Vincent L.
, p. 303 - 324 (2007/10/03)
The preparation and assessment of biological activity of 6-substituted 2-naphthamidine inhibitors of the serine protease urokinase plasminogen activator (uPA, or urokinase) is described. 2-Naphthamidine was chosen as a starting point based on synthetic considerations and on modeling of substituent vectors. Phenyl amides at the 6-position were found to improve binding; replacement of the amide with other two-atom linkers proved ineffective. The phenyl group itself is situated near the S1′ subsite; substitutions off of the phenyl group accessed S1′ and other distant binding regions. Three new points of interaction were defined and explored through ring substitution. A solvent-exposed salt bridge with the Asp60A carboxylate was formed using a 4-alkylamino group, improving affinity to Ki = 40 nM. Inhibitors also accessed two hydrophobic regions. One interaction is characterized by a tight hydrophobic fit made with a small dimple largely defined by His57 and His99; a weaker, less specific interaction involves alkyl groups reaching into the broad prime-side protein binding region near Val41 and the Cys42-Cys58 disulfide, displacing water molecules and leading to small gains in activity. Many inhibitors accessed two of these three regions. Affinities range as low as Ki = 6 nM, and many compounds had Ki 100 nM, while moderate to excellent selectivity was gained versus four of five members of a panel of relevant serine proteases. Also, some selectivity against trypsin was generated via the interaction with Asp60A. X-ray structures of many of these compounds were used to inform our inhibitor design and to increase our understanding of key interactions. In combination with our exploration of 8-substitution patterns, we have identified a number of novel binding interactions for uPA inhibitors.
Urokinase inhibitors
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, (2008/06/13)
Compounds having the formula are inhibitors of urokinase and are useful in the treatment of diseases in which urokinase plays a role. Also disclosed are urokinase-inhibiting compositions and a method of inhibiting urokinase in a mammal.
Ukokinase inhibitors
-
, (2008/06/13)
Compounds having the formula are inhibitors of urokinase and are useful in the treatment of diseases in which urokinase plays a role. Also disclosed are urokinase-inhibiting compositions and a method of inhibiting urokinase in a mammal.
