697762-43-9Relevant academic research and scientific papers
Macrolide and carbostyril heterocomplex and preparation method thereof
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Paragraph 0197; 0198, (2019/07/08)
The invention provides a macrolide and carbostyril heterocomplex. The macrolide and carbostyril heterocomplex is characterized by comprising compounds shown in the formula I and the formula II, or thecompounds shown in the formula I and the formula II and
Erythromycin derivative and preparing method thereof
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Paragraph 0188-0189, (2019/07/08)
The invention provides an erythromycin derivative. The erythromycin derivative is characterized by comprising a compound in a general formula I or comprising pharmaceutically-acceptable salt formed with the compound in the general formula I and inorganic
Design, synthesis and structure-activity relationships of novel macrolones: Hybrids of 2-fluoro 9-oxime ketolides and carbamoyl quinolones with highly improved activity against resistant pathogens
Ma, Cong-Xuan,Lv, Wei,Li, Ya-Xin,Fan, Bing-Zhi,Han, Xu,Kong, Fan-Sheng,Tian, Jing-Chao,Cushman, Mark,Liang, Jian-Hua
supporting information, p. 1 - 20 (2019/03/08)
Constitutively erythromycin-resistant apathogens are more difficult to address than inducibly resistant and efflux-resistant strains. Three series of the 4th generation 2-fluoro 9-oxime erythromycin ketolides were synthesized and evaluated. Incorporation of substituted heteroaryl groups (a - m), in contrast to previously reported the unsubstituted heteroaryl groups, proved to the beneficial for enhancement of the activities of the 9-propgargyl ketolide 8 series and the 9-allyl ketolide 14 series. But these aryl groups (a - m) cannot supply the resulting compounds 8 and 14, unlike corresponding the 6-allyl ketolide 20 series, with activity against constitutively resistant Streptococcus pneumoniae. However, hybrids of macrolides and quinolones (8, 14 and 20, Ar = n - t) exhibited not only high activities against susceptible, inducibly erm-mediated resistant, and efflux-mediated resistant strains, but also significantly improved potencies against constitutively resistant Streptococcus pneumoniae and Streptococcus pyogenes. The capacity was highlighted by introduction of newly designed carbamoyl quinolones (q, r, s and t) rather than commonly seen carboxy quinolones (o and p) as the pharmacophores. Structure-activity relationships and molecular modelling indicated that 8r, 14r and 20q may have different binding sites compared to current erythromycins. Moreover, 8r, 14r and 20q have 2.5–3.6 times prolonged half-life and 2.3- to 2.6-fold longer mean residence time in vivo over telithromycin. These findings pave the way for rational design of novel non-telithromycin macrolides that target new binding sites within bacterial ribosomes.
4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B
Zhi, Ying,Gao, Li-Xin,Jin, Yi,Tang, Chun-Lan,Li, Jing-Ya,Li, Jia,Long, Ya-Qiu
, p. 3670 - 3683 (2014/07/07)
Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC 50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.
Synthesis and biological activity of 4″-O-acyl derivatives of 14- and 15-membered macrolides linked to ω-quinolone-carboxylic unit
Kugor, Maja Matanovi?,Timac, Vlado,Palej, Ivana,Lugari?, Urdjica,Paljetak, Hana Ipi?,Fili?, Darko,Modri?, Marina,Ilovi?, Ivica,Gembarovski, Dubravka,Mutak, Stjepan,Erakovi? Haber, Vesna,Holmes, David J.,Ivezi?-Schoenfeld, Zrinka,Alihodi?, Sulejman
experimental part, p. 6547 - 6558 (2010/10/03)
The synthesis and antimicrobial activity of a new class of macrolide antibiotics which consist of a macrolide scaffold and a quinolone unit covalently connected by an appropriate linker are described. Optimization of several synthetic steps and structural
Initial Scale-Up and Process Improvements for the Preparation of a Lead Antibacterial Macrolone Compound
Stimac, Vlado,Matanovic Skugor, Maja,Palej Jakopovic, Ivana,Vinter, Adrijana,Ilijas, Marina,Alihodzc, Sulejman,Mutak, Stjepan
experimental part, p. 1393 - 1401 (2011/09/20)
Macrolones are a novel class of potent antimicrobial agents that consist of a macrolide scaffold to which a quinolone unit is tethered by various linkers to the 4 -O-position of the cladinose sugar. In this paper is described a modified 13-step route to a
HETEROCYCLIC UREA DERIVATIVES AND METHODS OF USE THEREOF
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Page/Page column 47, (2010/12/29)
Compounds of formula (IA) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors
Sato, Motohide,Kawakami, Hiroshi,Motomura, Takahisa,Aramaki, Hisateru,Matsuda, Takashi,Yamashita, Masaki,Ito, Yoshiharu,Matsuzaki, Yuji,Yamataka, Kazunobu,Ikeda, Satoru,Shinkai, Hisashi
experimental part, p. 4869 - 4882 (2010/03/02)
Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto - enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited-marked antiretroviral activity. Here, we show the synthesis and the detailed structure - activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3,3- dimethylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nMin the strand transfer assay and an ED50 of 0.6 nMin the antiviral assay, and 6-(3-chloro-2-fluorobenzyl) -1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid 49, which had an IC50 of 7.2 nMand an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrasecatalyzed strand transfer processes than 3′-processing reactions, as is the case with the keto - enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.
4''-Substituted Erythromycin Derivative
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Page/Page column 14-15, (2008/12/04)
A compound of formula (I) and/or pharmaceutically acceptable derivatives thereof, having antimicrobial activity, processes for their preparation, compositions containing them and to their use in medicine.
6- (Heterocyclyl-substituted Benzyl) -4-Oxoquinoline Compound and Use Thereof as HIV Integrase Inhibitor
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Page/Page column 50, (2008/12/08)
The present invention relates to a compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutical composition, an anti-HIV
