132259-54-2Relevant articles and documents
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 00269; 00273, (2019/06/11)
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.
Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface
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
, p. 5020 - 5033 (2018/05/29)
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.
Aminopropyl-substituted tropane amine compound and its pharmaceutical composition, preparation method and use
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Paragraph 0077; 0082; 0083, (2017/08/29)
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
Preparation and activities of macromolecule conjugates of the CCR5 antagonist maraviroc
Asano, Shigehiro,Gavrilyuk, Julia,Burton, Dennis R.,Barbas, Carlos F.
supporting information, p. 133 - 137 (2014/03/21)
CCR5 antagonists are among the most advanced approaches in HIV therapy and may also be relevant to treatment of graft-versus-host disease and Staphylococcus aureus infection. To expand the potential of the only approved CCR5 antagonist, Maraviroc, we studied derivatives that would enable functional linkage of Maraviroc to long-lived carriers. Through targeted synthesis, we discovered an effective linkage site on Maraviroc and demonstrate the potential of these derivatives to prepare potent chemically programmed antibodies and PEGylated derivatives. The resulting compounds effectively neutralized a variety of HIV-1 isolates. Both chemically programmed antibody and PEGylation approaches extend the neutralization activity of serum circulating Maraviroc. Derivation of a successful conjugation strategy for Maraviroc should further enable its use in chemically programmed vaccines, novel bispecific antibodies, and topical microbicides.
1,4 DI SUBSTITUTED PYRROLIDINE - 3 - YL -AMINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF METABOLIC DISORDERS
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Page/Page column 20, (2012/06/01)
Therapeutic compounds are disclosed having the general formula (1) that are useful for the treatment of metabolic disorders, including type II diabetes.The compounds have activity as agonists of GPR1 19. Compounds having the stereochemistry of formula (la) may also demonstrate DPP-IV inhibitory activity.
AMIDE COMPOUNDS, THEIR PHARMACEUTICAL COMPOSITIONS, THEIR PREPARATION METHOD AND THEIR USES
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Page/Page column 5, (2011/10/19)
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).
Design and synthesis of 6-fluoro-2-naphthyl derivatives as novel CCR3 antagonists with reduced CYP2D6 inhibition
Sato, Ippei,Morihira, Koichiro,Inami, Hiroshi,Kubota, Hirokazu,Morokata, Tatsuaki,Suzuki, Keiko,Iura, Yosuke,Nitta, Aiko,Imaoka, Takayuki,Takahashi, Toshiya,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-ichi
, p. 8607 - 8618 (2008/12/23)
In our previous study on discovering novel types of CCR3 antagonists, we found a fluoronaphthalene derivative (1) that exhibited potent CCR3 inhibitory activity with an IC50 value of 20 nM. However, compound 1 also inhibited human cytochrome P450 2D6 (CYP2D6) with an IC50 value of 400 nM. In order to reduce its CYP2D6 inhibitory activity, we performed further systematic structural modifications on 1. In particular, we focused on reducing the number of lipophilic moieties in the biphenyl part of 1, using C log D7.4 values as the reference index of lipophilicity. This research led to the identification of N-{(3-exo)-8-[(6-fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-3-(piperidin-1-ylcarbonyl)isonicotinamide 1-oxide (30) which showed comparable CCR3 inhibitory activity (IC50 = 23 nM) with much reduced CYP2D6 inhibitory activity (IC50 = 29,000 nM) compared with 1.
Novel 3beta-amino azabicyclooctane heteroaromatic amid derivatives preparation method and therapeutic uses thereof
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Page/Page column 9, (2010/02/11)
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.
Quinolone Antibacterials: Preparation and Activity of Bridged Bicyclic Analogues of the C7-Piperazine
Kiely, John S.,Hutt, Marland P.,Culbertson, Townley P.,Bucsh, Ruth A.,Worth, Donald F.,et al.
, p. 656 - 663 (2007/10/02)
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.
