410544-37-5Relevant academic research and scientific papers
Identification and Optimization of a Series of 8-Hydroxy Naphthyridines with Potent in Vitro Antileishmanial Activity: Initial SAR and Assessment of in Vivo Activity
Thomas, Michael G.,De Rycker, Manu,Wall, Richard J.,Spinks, Daniel,Epemolu, Ola,Manthri, Sujatha,Norval, Suzanne,Osuna-Cabello, Maria,Patterson, Stephen,Riley, Jennifer,Simeons, Frederick R. C.,Stojanovski, Laste,Thomas, John,Thompson, Stephen,Naylor, Claire,Fiandor, Jose M.,Wyatt, Paul G.,Marco, Maria,Wyllie, Susan,Read, Kevin D.,Miles, Timothy J.,Gilbert, Ian H.
, p. 9523 - 9539 (2020/10/19)
Visceral leishmaniasis (VL) is a parasitic infection that results in approximately 26 ?000-65 ?000 deaths annually. The available treatments are hampered by issues such as toxicity, variable efficacy, and unsuitable dosing options. The need for new treatments is urgent and led to a collaboration between the Drugs for Neglected Diseases initiative (DNDi), GlaxoSmithKline (GSK), and the University of Dundee. An 8-hydroxynaphthyridine was identified as a start point, and an early compound demonstrated weak efficacy in a mouse model of VL but was hampered by glucuronidation. Efforts to address this led to the development of compounds with improved in vitro profiles, but these were poorly tolerated in vivo. Investigation of the mode of action (MoA) demonstrated that activity was driven by sequestration of divalent metal cations, a mechanism which was likely to drive the poor tolerability. This highlights the importance of investigating MoA and pharmacokinetics at an early stage for phenotypically active series.
Chemo-selective Suzuki–Miyaura reactions: Synthesis of highly substituted [1,6]-naphthyridines
Suneel Kumar, Yadavalli,Nawaz Khan, Fazlur-Rahman
, p. 1607 - 1612 (2017/07/17)
The Suzuki-Miyaura reaction of methyl-5-bromo-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (5), with 2 equiv. of arylboronic acids gave diarylated product, 5,8–diaryl-1,6-naphthyridine-7-carboxylate (7), whereas 1 equiv. of arylboronic acid resulted in site-selective formation of 5-aryl-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (8). The reactions proceeded with excellent chemo-selectivity in favor of the bromide group. Likewise, one-pot reaction with completely different boronic acids by sequential addition produced 1,6-naphthyridine-7-carboxylates, (10) containing two different aryl groups at 5 and 8 positions.
Three substituted naphthyridine compounds and its preparation and use
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Paragraph 0073-0075, (2017/04/14)
The invention relates to 1,3,5-tri-substituted-1H-imidazo[4,5-h]1,6-diazanaphthalene-2(3H)-one compounds shown as the general formula I, isomers thereof and pharmaceutically acceptable salts thereof, a preparation method and applications thereof, and comp
Copper-catalyzed C-N coupling in the synthesis of integrase inhibitors of immunodeficiency viruses
Lin, Jinguan,Houpis, Ioannis N.,Liu, Renmao,Wang, Youchu,Zhang, Jianqian
, p. 205 - 214 (2014/05/20)
This contribution describes the total synthesis of a complex macrocyclic integrase inhibitor, a key enzyme involved in the infection process of various immunodeficiency viruses. The key transformation of the synthetic strategy was the selective C-N coupling of a sulfonamide to a heteroaryl bromide in the presence of potentially competing amide and carbamate functionalities. The transformation was accomplished with CuI catalysis using bypiridine as the ligand in the presence of base and enabled a convergent approach to the target molecule.
Repositioning HIV-1 integrase inhibitors for cancer therapeutics: 1,6-naphthyridine-7-carboxamide as a promising scaffold with drug-like properties
Zeng, Li-Fan,Wang, Yong,Kazemi, Roza,Xu, Shili,Xu, Zhong-Liang,Sanchez, Tino W.,Yang, Liu-Meng,Debnath, Bikash,Odde, Srinivas,Xie, Hua,Zheng, Yong-Tang,Ding, Jian,Neamati, Nouri,Long, Ya-Qiu
, p. 9492 - 9509 (2013/01/16)
Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories. In spite of its remarkable potency and efficacy, unfortun
AZA-QUINOLINOL PHOSPHONATE INTEGRASE INHIBITOR COMPOUNDS
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Page/Page column 58; 60, (2008/06/13)
Aza-quinolinol phosphonate compounds and methods for inhibition of HIV-integrase are disclosed. Formula (I). Ar is aryl or heteroaryl connecting R6 to L. L is a bond or a linker connecting a ring atom of Ar to N. The ring atoms, X1-X5 may be N, substituted nitrogen, or substituted carbon, and form rings. The compounds include at least one phosphonate group covalently attached at any site.
NAPHTHYRIDINE INTEGRASE INHIBITORS
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Page 70, (2010/02/09)
The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors
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, (2008/06/13)
Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described. These compounds are inhibitors of HIV integrase and inhibitors of HIV replication, and are useful in the
Sodium salt of an HIV integrase inhibitor
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, (2008/06/13)
A sodium salt of Compound A is disclosed, wherein Compound A is of formula: Compound A is an HIV integrase inhibitor useful for preventing or treating HIV infection, for delaying the onset of AIDS, and for treating AIDS.
