1033748-33-2Relevant academic research and scientific papers
Novel N-linked aminopiperidine-based gyrase inhibitors with improved hERG and in vivo efficacy against mycobacterium tuberculosis
Hameed P, Shahul,Patil, Vikas,Solapure, Suresh,Sharma, Umender,Madhavapeddi, Prashanti,Raichurkar, Anandkumar,Chinnapattu, Murugan,Manjrekar, Praveena,Shanbhag, Gajanan,Puttur, Jayashree,Shinde, Vikas,Menasinakai, Sreenivasaiah,Rudrapatana, Suresh,Achar, Vijayashree,Awasthy, Disha,Nandishaiah, Radha,Humnabadkar, Vaishali,Ghosh, Anirban,Narayan, Chandan,Ramya,Kaur, Parvinder,Sharma, Sreevalli,Werngren, Jim,Hoffner, Sven,Panduga, Vijender,Kumar, C. N. Naveen,Reddy, Jitendar,Kumar Kn, Mahesh,Ganguly, Samit,Bharath, Sowmya,Bheemarao, Ugarkar,Mukherjee, Kakoli,Arora, Uma,Gaonkar, Sheshagiri,Coulson, Michelle,Waterson, David,Sambandamurthy, Vasan K.,De Sousa, Sunita M.
, p. 4889 - 4905 (2014)
DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. Biochemical studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. The compounds are highly bactericidal against extracellular as well as intracellular Mtb. Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. Compounds from this series are efficacious in various murine models of tuberculosis.
PYRROLO[2,1-F][1,2,4]TRIAZINE DERIVATIVES SERVING AS SELECTIVE HER2 INHIBITORS AND APPLICATION THEREOF
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, (2021/03/18)
The present invention relates to a group of pyrrolo[2, 1-f][1,2,4]triazine derivatives serving as selective HER2 inhibitors and an application thereof in the preparation of a drug that serves as an HER2 inhibitor. Specifically, the present invention relates to a compound represented by formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof.
BETA-LACTAMASE INHIBITORS
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Paragraph 00227, (2014/10/04)
Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.
Optimization of pyrrolamide topoisomerase II inhibitors toward identification of an antibacterial clinical candidate (AZD5099)
Basarab, Gregory S.,Hill, Pamela J.,Garner, C. Edwin,Hull, Ken,Green, Oluyinka,Sherer, Brian A.,Dangel, P. Brian,Manchester, John I.,Bist, Shanta,Hauck, Sheila,Zhou, Fei,Uria-Nickelsen, Maria,Illingworth, Ruth,Alm, Richard,Rooney, Mike,Eakin, Ann E.
, p. 6060 - 6082 (2014/08/18)
AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.
Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II with reduced p K a: Antibacterial agents with an improved safety profile
Reck, Folkert,Alm, Richard A.,Brassil, Patrick,Newman, Joseph V.,Ciaccio, Paul,McNulty, John,Barthlow, Herbert,Goteti, Kosalaram,Breen, John,Comita-Prevoir, Janelle,Cronin, Mark,Ehmann, David E.,Geng, Bolin,Godfrey, Andrew Aydon,Fisher, Stewart L.
, p. 6916 - 6933 (2012/10/07)
Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. N-L
NEW COMPOUNDS
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Page/Page column 34, (2010/07/10)
The present invention encompasses compounds of general formula (1) wherein A, B, X, R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and t
2-QUINOLINONE AND 2-QUINOXALINONE- DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS
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Page/Page column 106, (2008/12/06)
The present invention relates to compounds of Formula (I) : and pharmaceutically acceptable salts thereof, to their use in the treatment of bacterial infections, and to their methods of preparation.
STEREOISOMERIC COMPOUNDS AND METHODS FOR THE TREATMENT OF GASTROINTESTINAL AND CENTRAL NERVOUS SYSTEM DISORDERS
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Page/Page column 37-38, (2010/02/13)
The subject invention provides stereoisomeric compounds of formula (X): wherein the variables are as defined herein, and compositions for the safe and effective treatment of various gastrointestinal disorders including, but not limited to, gastroparesis,
