24306-33-0Relevant academic research and scientific papers
Discovery of Inhibitors of the Lipopolysaccharide Transporter MsbA: From a Screening Hit to Potent Wild-Type Gram-Negative Activity
Verma, Vishal A.,Wang, Lan,Labadie, Sharada S.,Liang, Jun,Sellers, Benjamin D.,Wang, Jian,Dong, Liting,Wang, Qiuyue,Zhang, Shuang,Xu, Zhongya,Zhang, Yexia,Niu, Yanan,Wang, Xinxin,Wai, John,Koehler, Michael F. T.,Hu, Huiyong,Alexander, Mary Kate,Nishiyama, Mireille,Miu, Anh,Xu, Yiming,Pang, Jodie,Katakam, Anand K.,Reichelt, Michael,Austin, Cary D.,Ho, Hoangdung,Payandeh, Jian,Koth, Christopher M.
supporting information, p. 4085 - 4120 (2022/03/02)
The dramatic increase in the prevalence of multi-drug resistant Gram-negative bacterial infections and the simultaneous lack of new classes of antibiotics is projected to result in approximately 10 million deaths per year by 2050. We report on efforts to target the Gram-negative ATP-binding cassette (ABC) transporter MsbA, an essential inner membrane protein that transports lipopolysaccharide from the inner leaflet to the periplasmic face of the inner membrane. We demonstrate the improvement of a high throughput screening hit into compounds with on-target single digit micromolar (μM) minimum inhibitory concentrations against wild-type uropathogenic Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. A 2.98 ? resolution X-ray crystal structure of MsbA complexed with an inhibitor revealed a novel mechanism for inhibition of an ABC transporter. The identification of a fully encapsulated membrane binding site in Gram-negative bacteria led to unique physicochemical property requirements for wild-type activity.
2'-(QUINOLIN-3-YL)-5',6'-DIHYDROSPIRO[AZETIDINE-3,4'-PYRROLO[1,2-B]PYRAZOLE]-1-CARBOXYLATE DERIVATIVES AND RELATED COMPOUNDS AS MAP4K1 (HPK1) INHIBITORS FOR THE TREATMENT OF CANCER
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Page/Page column 100, (2021/12/31)
The present invention relates to Map4K1 inhibitors of formula (I), to pharmaceutical compositions and combinations comprising the compounds according to the invention, and to the prophylactic and therapeutic use of the inventive compounds, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular for neoplastic disorders, respectively cancer or conditions with dysregulated immune responses or other disorders associated with aberrant MAP4K1 signaling, as a sole agent or in combination with other active ingredients. The present invention further relates to the use, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of protein inhibitors in benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, in neurodegenerative disorders, in inflammatory disorders, in atherosclerotic disorders and in male fertility control.
SUBSTITUTED 1,5-NAPHTHYRIDINES OR QUINOLINES AS ALK5 INHIBITORS
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Paragraph 410; 411, (2021/05/29)
The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.
ALK5 INHIBITORS
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Paragraph 0917; 0918, (2020/07/07)
The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.
SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
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Paragraph 0229, (2019/10/15)
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
Quinoline compounds and preparation method thereof, and intermediate, pharmaceutical composition and application of quinoline compounds
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Paragraph 0830-0832, (2018/02/04)
The invention discloses quinoline compounds and a preparation method thereof, and an intermediate, a pharmaceutical composition and application of quinoline compounds. The invention provides quinoline compounds disclosed as Formula 1, and pharmaceutically acceptable salts, solvates, metabolites, metabolism precursors or pharmaceutical precursors thereof. The quinoline compounds have favorable inhibitory effects on tyrosine kinase C-Met, and can be used for preparing drugs for prevention, treatment or auxiliary treatment on multiple diseases related to C-Met expression or activity, and especially neoplastic diseases.
6 - SUBSTITUTED 3 - (QUINOLIN- 6 - YLTHIO) - [1,2,4] TRIAZOLO [4, 3 -A] PYRADINES AS TYROSINE KINASE
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Page/Page column 75, (2013/03/28)
The invention relates to compounds of formula (I) and salts thereof: Formula (I) wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
TRIAZOLOPYRIDINE COMPOUNDS
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Paragraph 0700, (2013/09/26)
The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound o f formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I)
[1,2,4] TRIAZOLO [4,3-B] PYRIDAZINE COMPOUNDS AS INHIBITORS OF THE C-MET TYROSINE KINASE
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Paragraph 0456; 0457, (2014/01/07)
The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
[1, 2, 4] TRIAZOLO [4, 3 -B] PYRIDAZINE COMPOUNDS AS INHIBITORS OF THE C-MET TYROSINE KINASE
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Page/Page column 63, (2012/08/28)
The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
