- Novel route to the synthesis of hydroxylated piperidine and pyrrolidine derivatives via the intramolecular reaction of γ-aminoallylstannane with aldehyde
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The Lewis acid mediated intramolecular reaction of gamma-aminoallyl-stannane 6 gave trans-beta-hydroxypiperidine derivative 7a as a major product. On the other hand, the thermal cyclization of 6 and 8 afforded cis-beta-hydroxypiperidine 7b and pyrrolidine derivative 9b, respectively, with very high stereoselectivity.
- Kadota, Isao,Kawada, Miho,Saya, Shioko,Yamamoto, Yoshinori
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Read Online
- De-novo designed β-lysine derivatives can both augment and diminish the proliferation rates of E. coli through the action of Elongation Factor P
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An investigation into the effect of modified β-lysines on the growth rates of eubacterial cells is reported. It is shown that the effects observed are due to the post translational modification of Elongation Factor P (EFP) with these compounds catalysed b
- Connon, Stephen J.,Ghanim, Magda,Kelly, Vincent P.,McDonnell, Ciara M.,Mike Southern, J.
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supporting information
(2022/01/24)
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- NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) comprises at least one covalently bound -ONO2 or -ONO moiety and at most four covalently bound -ONO2 or -ONO moieties, and wherein AR, R1, X, R3 and R4 are as defined in claim 1; and pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.
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Page/Page column 113
(2021/12/28)
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- ANTIFUNGAL PEPTOIDS
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Described herein are antifungal peptoids, the development and characterization of the antifungal peptoids, methods of making the antifungal peptoids, and methods of using the antifungal peptoids. In some embodiments, the antifungal peptoids may be administered to a subject infected with or at risk of being infected with pathogenic fungi including, for example Cryptococcus spp. In some embodiments, the Cryptococcus spp. may include C. neoformans or C. gattii or both.
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Paragraph 0076
(2020/07/07)
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- Improved potency and reduced toxicity of the antifungal peptoid AEC5 through submonomer modification
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As proteolytically stable peptidomimetics, peptoids could serve as antifungal agents to supplement a therapeutic field wrought with toxicity issues. We report the improvement of an antifungal peptoid, AEC5, through an iterative structure-activity relationship study. A sarcosine scan was used to first identify the most pharmacophorically important peptoid building blocks of AEC5, followed by sequential optimization of each building block. The optimized antifungal peptoid from this study, β-5, has improved potency towards Cryptococcus neoformans and decreased toxicity towards mammalian cells. For example, the selectivity ratio for C. neoformans over mammalian fibroblasts was improved from 8 for AEC5 to 37 for β-5.
- Middleton, Madyson P.,Armstrong, Scott A.,Bicker, Kevin L.
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supporting information
p. 3514 - 3519
(2018/10/15)
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- NANOPARTICLES FOR DRUG DELIVERY
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The invention provides therapeutic magnetic nanoparticles containing a therapeutic agent connected to a magnetic nanoparticle core through a stable functional group and a linker that can be induced to release the therapeutic agent from the core, through h
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Page/Page column 54; 55
(2016/04/20)
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- Intramolecular thermal stepwise [2 + 2] cycloadditions: Investigation of a stereoselective synthesis of [n.2.0]-bicyclolactones
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Fused cyclobutanes are found in a range of natural products and formation of these motifs in a straightforward and easy manner represents an interesting synthetic challenge. To this end we investigated an intramolecular variant of the thermal enamine [2 + 2] cyclisation, developing a diastereoselective intramolecular enamine [2 + 2] cyclisation furnishing δ lactone and lactam fused cyclobutenes in good yield and excellent diastereoselectivity.
- Throup, Adam,Patterson, Laurence H.,Sheldrake, Helen M.
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supporting information
p. 9554 - 9559
(2016/10/22)
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- RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
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Compounds of Formula (I): wherein R1, R2 and R3 are defined herein, are useful as inhibitors of RSV.
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Page/Page column 54
(2015/05/19)
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- METHOD OF PREPARING ETHACRYNIC AMIDE DERIVATIVES AND APPLICATION THEREOF
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The present invention provides a method for preparing [18F]—N-(4-fluorobutyl)ethacrynic amide which is prepared from radiofluorination and deprotection of the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)-butyl)ethacrynic amide], obtained from ethacrynic acid via 6-step synthesis in 39% yield, in a radiochemical yield of 44%, aspecific activity of 48 GBq/μmol and radiochemical purity of 98%. The present invention further provides a composition for positron emission tomography (PET) of an animal models of a tumor liver or a liver disease, comprising [18F]—N-(4-fluorobutyl)ethacrynic amide and a pharmaceutically acceptable carrier.
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Paragraph 0043
(2013/06/28)
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- Trianion synthon approach to spirocyclic heterocycles
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A variety of spirocyclic heterocycles have been constructed by a double-alkylation and reductive cyclization approach utilizing α-heteroatom nitriles as trianion synthons. The method provides access to heteroatom-substituted spirocycles in a variety of ring sizes that are found in natural products and are important in pharmaceutical lead development and optimization.
- Perry, Matthew A.,Hill, Richard R.,Rychnovsky, Scott D.
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supporting information
p. 2226 - 2229
(2013/06/05)
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- Direct stereospecific amination of alkyl and aryl pinacol boronates
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The direct amination of alkyl and aryl pinacol boronates is accomplished with lithiated methoxyamine. This reaction directly provides aliphatic and aromatic amines, stereospecifically, and without preactivation of the boronate substrate.
- Mlynarski, Scott N.,Karns, Alexander S.,Morken, James P.
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supporting information
p. 16449 - 16451,3
(2020/09/15)
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- Synthesis and evaluation of [18F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase
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[18F]Flurobutyl ethacrynic amide ([18F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl] ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [ 18F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [18F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [18F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [18F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [18F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.
- Huang, Ho-Lien,Yeh, Chun-Nan,Chang, Kang-Wei,Chen, Jenn-Tzong,Lin, Kun-Ju,Chiang, Li-Wu,Jeng, Kee-Ching,Wang, Wei-Ting,Lim, Ken-Hong,Chen, Caleb Gonshen,Lin, Kun-I,Huang, Ying-Cheng,Lin, Wuu-Jyh,Yen, Tzu-Chen,Yu, Chung-Shan
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supporting information; experimental part
p. 3998 - 4003
(2012/07/13)
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- NEW COMPOUNDS I/418
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There is provided compounds of formula I, wherein R1 to R7 have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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Page/Page column 29
(2008/06/13)
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- SUBSTITUTED 4H-IMIDAZO [4, 5, 1-IJ] [1, 6] NAPHTHYRIDINE-9-AMINES AND THEIR PHARMACEUTICAL USE
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Substituted 4H-imidazo[4,5, 1-ij][1,6]naphthyridine-9-amines of the Formula I : pharmaceutical compositions containing the compounds, intermediates, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases, are disclosed.
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Page/Page column 52
(2010/11/30)
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- Effective methods for the biotinylation of azamacrocycles
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(Chemical Equation Presented) The biotin-(strept)avidin interaction remains a gold standard of model biological recognition events. The biotinylation of azamacrocycles permits the investigation of signal transduction between this recognition event and the
- Krivickas, Sara J.,Tamanini, Emiliano,Todd, Matthew H.,Watkinson, Michael
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p. 8280 - 8289
(2008/02/13)
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- HIV INTEGRASE INHIBITORS
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Tricyclic compounds of Formula (I) are inhibitors of HIV integrase and inhibitors of HIV replication: wherein bond a, ring A, Rl, R2 and R3 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
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Page/Page column 65-66
(2008/06/13)
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- Estra-1,3,5 (10)-triene derivatives
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Provided is steroid sulfatase inhibitors comprising, as the active ingredient, an estra-1,3,5(10)-triene derivative which is represented by formula (I): {wherein R1 and R2 are the same or different and represent a hydrogen atom, a lower alkyl group or, etc.; R3 represents a hydrogen atom etc.; R4 represents a hydrogen atom etc.; R5 represents a hydrogen atom etc.; R6 represents a cyano group, an amino group, COR53 (wherein R53 represents a substituted lower alkyl group etc.), a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, etc}, or pharmaceutically acceptable salts thereof.
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- Design, synthesis and evaluation of D-Homophenylalanyl epoxysuccinate inhibitors of the trypanosomal cysteine protease cruzain
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The binding modes of E-64c to papain combined with molecular modeling and ligand design using the crystal structure of cruzain have been used to develop new, potent D-Homophenylalanyl epoxysuccinate inhibitors of cruzain, the major cysteine protease of Tr
- Roush, William R,Hernandez, Alejandro Alvarez,McKerrow, James H,Selzer, Paul M,Hansell, Elizabeth,Engel, Juan C
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p. 9747 - 9762
(2007/10/03)
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