Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage N-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore

2013 ◽  
Vol 78 (6) ◽  
pp. 2661-2669 ◽  
Author(s):  
Che-Wah Lee ◽  
Ricardo Lira ◽  
Jason Dutra ◽  
Kevin Ogilvie ◽  
Brian T. O’Neill ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Late Stage ◽  
Stereoselective Synthesis ◽  
Aspartyl Protease ◽  
Bace 1 ◽  
Aspartyl Protease Inhibitors

Synthesis of New Substituted 4,5-Dihydro-3H-spiro[1,5]-benzoxazepine-2,4′-piperidine and Biological Properties

2006 ◽  
Vol 59 (11) ◽  
pp. 812 ◽  
Author(s):  
Younes Laras ◽  
Nicolas Pietrancosta ◽  
Vincent Moret ◽  
Sylvain Marc ◽  
Cédrik Garino ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Functional Groups ◽  
Biological Properties ◽  
Hiv Protease ◽  
Aspartyl Protease ◽  
Electronic Effects ◽  
The Creation ◽  
Hiv 1 ◽  
Bace 1 ◽  
Aspartyl Protease Inhibitors

The reduction of substituted spiro-piperidinyl chromanone oximes with DIBAH reagents has been known to afford the corresponding substituted 4,5-dihydro-3H-spiro[1,5]-benzoxazepine-2,4′-piperidine. The position and electronic effects of the substituents on the aryl moiety control the observed rearrangement. Spiro-benzoxazepine analogue 5j represents a key intermediate for the creation of a library of diverse potential bioactive drugs. With three functional groups that could be selectively and orthogonally protected, many different substituents can be introduced. The obtained analogues were assayed as the possible aspartyl protease inhibitors HIV protease (HIV-1), and β-secretase (BACE-1).

Analogues of Key Precursors of Aspartyl Protease Inhibitors:  Synthesis of Trifluoromethyl Amino Epoxides

2005 ◽  
Vol 70 (2) ◽  
pp. 699-702 ◽  
Author(s):  
Nguyen Thi Ngoc Tam ◽  
Guillaume Magueur ◽  
Michèle Ourévitch ◽  
Benoit Crousse ◽  
Jean-Pierre Bégué ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Aspartyl Protease ◽  
Aspartyl Protease Inhibitors

HIV aspartyl protease inhibitors modify the percentage of activated leukocytes, as well as serum levels of IL-17A and NO during experimental leishmaniasis

2018 ◽  
Vol 60 ◽  
pp. 179-188 ◽  
Author(s):  
Daniele Luísa Ribeiro Alvarenga ◽  
Amanda Helen dos Santos Silva ◽  
Jacqueline Araújo Fiuza ◽  
Soraya Torres Gaze ◽  
Jaquelline Germano de Oliveira ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Serum Levels ◽  
Aspartyl Protease ◽  
Aspartyl Protease Inhibitors

scholarly journals Novel aspartyl protease inhibitors, YF-0200R-A and B.

1994 ◽  
Vol 47 (5) ◽  
pp. 566-570 ◽  
Author(s):  
TSUTOMU SATO ◽  
KOJI NAGAI ◽  
MITSUYOSHI SHIBAZAKI ◽  
KENJI ABE ◽  
YUKIHIRO TAKEBAYASHI ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Aspartyl Protease ◽  
Aspartyl Protease Inhibitors

scholarly journals Combination of antifungal drugs and protease inhibitors prevent Candida albicans biofilm formation and disrupt mature biofilms

2020 ◽  
Author(s):  
Matthew B. Lohse ◽  
Megha Gulati ◽  
Charles S. Craik ◽  
Alexander D. Johnson ◽  
Clarissa J. Nobile
Keyword(s):  
Candida Albicans ◽  
Protease Inhibitors ◽  
Amphotericin B ◽  
Biofilm Formation ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Aspartyl Protease ◽  
Abiotic Surfaces ◽  
Drug Concentrations ◽  
Aspartyl Protease Inhibitors

AbstractBiofilms formed by the fungal pathogen Candida albicans are resistant to many of the antifungal agents commonly used in the clinic. Previous reports suggest that protease inhibitors, specifically inhibitors of aspartyl proteases, could be effective antibiofilm agents. We screened three protease inhibitor libraries, containing a total of 80 compounds for the abilities to prevent C. albicans biofilm formation and to disrupt mature biofilms. The compounds were screened individually and in the presence of subinhibitory concentrations of the most commonly prescribed antifungal agents for Candida infections: fluconazole, amphotericin B, or caspofungin. Although few of the compounds affected biofilms on their own, seven aspartyl protease inhibitors inhibited biofilm formation when combined with amphotericin B or caspofungin. Furthermore, nine aspartyl protease inhibitors disrupted mature biofilms when combined with caspofungin. These results suggest that the combination of standard antifungal agents together with specific protease inhibitors may be useful in the prevention and treatment of C. albicans biofilm infections.ImportanceCandida albicans is one of the most common pathogens of humans. C. albicans forms biofilms, structured communities of cells several hundred microns thick, on both biotic and abiotic surfaces. These biofilms are typically resistant to antifungal drugs at the concentrations that are normally effective against free-floating cells, thus requiring treatment with higher drug concentrations that often have significant side effects. Here, we show that certain combinations of existing antifungal agents with protease inhibitors, including several drugs already commonly used to treat HIV patients, are effective at inhibiting biofilm formation by C. albicans and/or at disrupting mature C. albicans biofilms.

scholarly journals An Aspartyl Protease Inhibitor Orthologue Expressed by Parelaphostrongylus tenuis Is Immunogenic in an Atypical Host

2002 ◽  
Vol 9 (4) ◽  
pp. 763-770 ◽  
Author(s):  
Michael S. Duffy ◽  
Nancy MacAfee ◽  
Michael D. B. Burt ◽  
Judith A. Appleton
Keyword(s):  
Protease Inhibitors ◽  
Adult Male ◽  
Red Deer ◽  
Parasitic Nematodes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aspartyl Protease ◽  
Native Protein ◽  
Male And Female ◽  
Parelaphostrongylus Tenuis ◽  
Aspartyl Protease Inhibitors

ABSTRACT Parelaphostrongylus tenuis is a neurotropic nematode common in white-tailed deer (Odocoileus virginianus) of eastern North America. This parasite is the causative agent of a debilitating neurologic disease in atypical hosts, including domestic livestock. In order to identify proteins of potential significance in the host-parasite relationship, a cDNA library was produced from adult P. tenuis mRNA. Screening the library with antisera from infected red deer (Cervus elaphus elaphus) and immunized AO strain rats, we identified clones with sequence similarities to aspartyl protease inhibitors from several parasitic nematodes. Antibody that was generated against this recombinant protein of P. tenuis (Pt-API-1) detected the native protein in E/S products, in muscle and gonad, and on the surface of the cuticle of adult male and female P. tenuis. The native protein was detected in internal structures of first-stage (L1) and third-stage (L3) larvae. Reverse transcription-PCR confirmed expression of Pt-api-1 in L1, L3, and adult male and female worms. Expression of Pt-API-1 throughout the life cycle of P. tenuis suggests an essential function. Antibodies specific for recombinant Pt-API-1 were detected by enzyme-linked immunosorbent assay in sera from 12 red deer experimentally infected with P. tenuis. Antibodies were detected within 28 to 56 days postinfection. Responses were sustained or biphasic in animals with patent infections, consistent with expression of Pt-API-1 by L1. Our results are compatible with findings in other parasitic nematodes showing that aspartyl protease inhibitors are highly immunogenic.

Short Total Synthesis of Aspartyl Protease Inhibitors L-685,434, L-682,679 and L-685,458

Synlett ◽  
2002 ◽  
Vol 2002 (11) ◽  
pp. 1845-1849 ◽  
Author(s):  
Luiz C. Dias ◽  
Andrea A. Ferreira ◽  
Gaspar Diaz
Keyword(s):  
Total Synthesis ◽  
Protease Inhibitors ◽  
Aspartyl Protease ◽  
Aspartyl Protease Inhibitors
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