75051-55-7Relevant articles and documents
Discovery of a Tricyclic β-Lactam as a Potent Antimicrobial Agent against Carbapenem-Resistant Enterobacterales, Including Strains with Reduced Membrane Permeability and Four-Amino Acid Insertion into Penicillin-Binding Protein 3: Structure-Activity-Relationships and In Vitro and In Vivo Activities
Sato, Jun,Kusano, Hiroki,Aoki, Toshiaki,Shibuya, Satoru,Yokoo, Katsuki,Komano, Kazuo,Oguma, Takuya,Matsumoto, Shuhei,Nakamura, Rio,Sato, Takafumi,Yamawaki, Kenji
, p. 400 - 410 (2022/02/19)
The current worldwide emergence of carbapenem-resistant enterobacterales (CREs) constitutes an important growing clinical and public health threat. Acquired carbapenemases are the most important determinants of resistance to carbapenems. In the development of the previously reported tricyclic β-lactam skeleton which exhibits potent antibacterial activities against several problematic β-lactamase-producing CREs without a β-lactamase inhibitor, we found that these activities were reduced against clinical isolates with resistance mechanisms other than β-lactamase production. These mechanisms were the reduction of outer membrane permeability with the production of β-lactamases and the insertion of four amino acids into penicillin-binding protein 3. Here, we report the discovery of a potent compound that overcomes these resistance mechanisms by the conversion of the alkoxyimino moiety of the aminothiazole side chain in which a hydrophilic functional group is introduced and the carboxylic acid of the alkoxyimino moiety is converted to reduce the negative charge of the whole molecule from 2 to 1. This potent tricyclic β-lactam is a promising drug candidate for infectious diseases caused by CREs due to its potent therapeutic efficacy in the neutropenic mouse lung infection model and low frequency of producing spontaneously resistant mutants.
Diazabicyclo compounds and application thereof
-
, (2020/06/09)
The invention belongs to the field of medical chemistry and, relates to diazabicyclo compounds and application thereof, and particularly provides compounds as shown in the formula (I) or isomers, pharmaceutically acceptable salts, solvates, crystals or pr
1,2,5-oxadiazole derivative used as indoleamine 2,3-dioxygenase inhibitor
-
, (2019/10/01)
The invention belongs to the technical field of 1,2,5-oxadiazole derivatives, and particularly relates to a 1,2,5-oxadiazole derivative or a pharmaceutically acceptable salt thereof which is used as an indoleamine 2,3-dioxygenase inhibitor. The structure of the 1,2,5-oxadiazole derivative or the pharmaceutically acceptable salt thereof used as the IDO inhibitor is shown in the following formula I.The invention provides a general formula compound I with a novel structure. Experimental results show that some compounds have excellent IDO inhibitory activity and permeation performance at the sametime. The compound is expected to be marketed as a tumor molecular immunotherapeutic drug for cancer treatment.
Beta-lactamase inhibitors and uses thereof
-
, (2018/10/24)
β-Lactamase inhibiting compounds, therapeutic methods of using the β-lactamase inhibiting compounds, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The β-lactamase inhibiting compounds are suitable for oral administration.
With tumor homing therapeutic polypeptide - drug conjugates and application thereof (by machine translation)
-
, (2017/08/25)
The present invention relates to guide treatment with tumor polypeptide - drug conjugates, polypeptide - drug conjugates preparation method and its application. The polypeptide of the invention - drug conjugates can be specific will PD0325901 analogs to d
The synthesis and BK channel-opening activity of N-acylaminoalkyloxime derivatives of dehydroabietic acid
Cui, Yong-Mei,Liu, Xin-Lan,Zhang, Wen-Ming,Lin, Hai-Xia,Ohwada, Tomohiko,Ido, Katsutoshi,Sawada, Kohei
, p. 283 - 287 (2016/01/09)
A series of N-acylaminoalkyloxime derivatives of dehydroabietic acid were synthesized and evaluated for BK channel-opening activities in an assay system of CHO-K1 cells expressing hBKα channels. The structure-activity relationship study revealed that a non-covalent interaction between the S atom of the 2-thiophene and the carbonyl O atom may contribute to conformation restriction for interaction with the ion channel. This research could guide the design and synthesis of novel abietane-based BK channel opener.
A PROCESS FOR PREPARATION OF (2S, 5R)-N-(2-AMINO ETHOXY)-6-(SULFOOXY)-7-OXO-1,6- DIAZABICYCLO [3.2.1] OCTANE-2-CARBOXAMIDE
-
, (2016/08/23)
A process for preparation of (2S,5R)-N-(2-aminoethoxy)-6-(sulfooxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carboxamide is disclosed. Formula (I)
NOVEL -LACTAMASE INHIBITOR AND METHOD FOR PRODUCING SAME
-
, (2015/04/15)
The currently available β-lactamase inhibitors are insufficient to inhibit the incessantly increasing β-lactamase, and novel β-lactamase inhibitors has been required today for the difficult treatment for bacterial infectious diseases caused by resistant bacteria which produce class C β-lactamase, extended-spectrum β-lactamase (ESBL) belonging to class A and D, or class A KPC-2 decomposing even carbapenem as a last resort for β-lactam antibiotic. A compound represented by the the formula (I), preparation process of the same, β-lactamase inhibitors and method for treating bacterial infectious diseases are provided.
Synthesis and biological evaluation of RGD-Conjugated MEK1/2 kinase inhibitors for integrin-targeted cancer therapy
Li, Xiaoxiao,Hou, Jianjun,Wang, Chao,Liu, Xinjie,He, Hongyan,Xu, Ping,Yang, Zhenjun,Chen, Zili,Wu, Yun,Zhang, Lihe
, p. 13957 - 13978 (2014/01/06)
Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor-PD0325901-have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9a-g showed anti-proliferation activity in melanoma A375 cells by the same mechanism as that of PD0325901. PEGylation increased the IC50 value of 9f three-fold in the A375 assay, and the multi-cRGD peptide cargo significantly improved the receptor specific anti-proliferation activity of 9g in integrin-overexpressing U87 cells. In the second series, RGD-PD0325901 13 exhibited significantly increased antitumor properties compared to the alkoxylamine analogs by both inhibition of the ERK pathway activity and DNA replication of the cancer cells. Furthermore, 13 displayed more potent anti-proliferation activity in the U87 assay than PD0325901 in a dose-dependent manner. All these data demonstrate that RGD-MEKI conjugates with an ester bond linkage enhanced anticancer efficacy with improved targeting capability toward integrin-overexpressing tumor cells.
OXIM DERIVATIVES AS HSP90 INHIBITORS
-
Page/Page column 154, (2009/09/05)
The invention relates to HSP90 inhibiting compounds consisting of the formula: (I) wherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.