80370-42-9Relevant articles and documents
HETEROARYL DERIVATIVES AS SEPIAPTERIN REDUCTASE INHIBITORS
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Paragraph 00441-00443, (2017/05/31)
Inhibitors of sepiapterin reductase of formula (I) or (I'), wherein the substituents are defined as in the claims, and uses of sepiapterin reductase inhibitors in analgesia, treatment of acute and chronic pain, anti-inflammation, and immune cell regulation are disclosed.
Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents
Zhao, Shizhen,Zhang, Xiangqian,Wei, Peng,Su, Xin,Zhao, Liyu,Wu, Mengya,Hao, Chenzhou,Liu, Chunchi,Zhao, Dongmei,Cheng, Maosheng
, p. 96 - 107 (2017/05/31)
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability.
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.
supporting information, p. 4889 - 4905 (2014/07/07)
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.
