- CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
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- Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface
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To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of the HIV-1 envelope (Env) gp120 protein and the host-cell coreceptor (CoR) protein can be covalently joined into bifunctional synergistic combinations with improved antiviral capabilities. A synthetic protocol was established to covalently combine a CCR5 small-molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components and, at the same time, exhibited low to subnanomolar potencies in inhibiting cell infection by different pseudoviruses, which were substantially greater than those of a noncovalent mixture of the individual components. The results demonstrate that targeting the virus-cell interface with a single molecule can result in improved potencies and also the introduction of new phenotypes to the chimeric inhibitor, such as the irreversible inactivation of HIV-1.
- Rashad, Adel A.,Song, Li-Rui,Holmes, Andrew P.,Acharya, Kriti,Zhang, Shiyu,Wang, Zhi-Long,Gary, Ebony,Xie, Xin,Pirrone, Vanessa,Kutzler, Michele A.,Long, Ya-Qiu,Chaiken, Irwin
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p. 5020 - 5033
(2018/05/29)
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- Aminopropyl-substituted tropane amine compound and its pharmaceutical composition, preparation method and use
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The invention belongs to the field of pharmaceutical chemistry and discloses a 8-(3-aminopropyl)-3-exo-8-azabicyclo[3. 2. 1]octane-3-amino-amide compound and its pharmaceutical composition and use. The compound or pharmacologically acceptable salt can be
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Paragraph 0077; 0084; 0085
(2017/08/29)
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- AMIDE COMPOUNDS, THEIR PHARMACEUTICAL COMPOSITIONS, THEIR PREPARATION METHOD AND THEIR USES
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The present invention pertains to the field of pharmaceutical chemistry and discloses 8-(3-aminopropyl)-3-exo-8-azabicyclo[3.2.1]octane-3-amino amide compounds represented by formula I, the pharmaceutical compositions, the preparation method and the use thereof. Such compounds or pharmaceutically acceptable salts thereof can be used as an antagonist of CCR5 in preparing medicaments for treating diseases mediated by CCR5, particularly HIV infection, asthma, rheumatoid arthritis, autoimmune diseases and chronic obstructive pulmonary diseases (COPD).
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Page/Page column 5
(2011/10/19)
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- Novel 3beta-amino azabicyclooctane heteroaromatic amid derivatives preparation method and therapeutic uses thereof
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The invention concerns compounds of general formula 1, wherein: A, B, D and E represent one or two nitrogen atoms, the others being carbon atoms; X represents a S or, a O, thereby forming a bicyclic fused heteroaromatic, such as thieno[2,3-b]pyridine, furo[2,3-b]pyridine, thieno[3,2-b]pyridine, furo[3,2-b]pyridine, thieno[2,3-b]pyrazine, furo[2,3-b]pyrazine, thieno[2,3-c]pyridine, furo[2,3-c]pyridine, thieno[3,2-c]pyridine and furo[3,2-c]pyridine; R1 represents a linear or branched C1-C6 alkoxy group, a linear or branched C1-C6 alkylthio group; R2 represents a linear, branched, cyclic C2-C8 group, a 2- or 3- thienylmethyl group, or a benzyl group optionally substituted by one or several halogens, F, Cl, Br, I, C1-C4 alkyl, C1-C4 alkoxy, CF3, CN, NO2, OH; and their pharmaceutically acceptable salts. Said compounds are anti-dopaminergic agents.
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Page/Page column 9
(2010/02/11)
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- Quinolone Antibacterials: Preparation and Activity of Bridged Bicyclic Analogues of the C7-Piperazine
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A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicycloalkanes, where n = 2, 3 and m = 1, 2, and a series including 4-aminopiperidine and 3-amino-8-azabicyclooctanes have been prepared and evaluated in vitro and in vivo for antibacterial activity against a variety of Gramm-negative and Gramm-positive organisms.These compounds were also tested against the target enzyme bacterial DNA gyrase.All the examples investigated are nearly equipotent with the parent 7-piperazinyl analogues.Only endo-7-(3-amino-8-azabicyclooct-8-yl) -1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid displays activity that surpasses that of the piperazine parent.
- Kiely, John S.,Hutt, Marland P.,Culbertson, Townley P.,Bucsh, Ruth A.,Worth, Donald F.,et al.
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p. 656 - 663
(2007/10/02)
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