- Synthesis and Structure–Activity Relationship Studies of Benzo[b][1,4]oxazin-3(4H)-one Analogues as Inhibitors of Mycobacterial Thymidylate Synthase X
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Since the discovery of a flavin-dependent thymidylate synthase (ThyX or FDTS) that is absent in humans but crucial for DNA biosynthesis in a diverse group of pathogens, the enzyme has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous screening efforts and report herein an optimization campaign of a novel series of inhibitors with a unique inhibition profile. The inhibitors display competitive inhibition toward the methylene tetrahydrofolate cofactor of ThyX, enabling us to generate a model of the compounds bound to their target, thus offering insight into their structure–activity relationships.
- Modranka, Jakub,Li, Jiahong,Parchina, Anastasia,Vanmeert, Michiel,Dumbre, Shrinivas,Salman, Mayla,Myllykallio, Hannu,Becker, Hubert F.,Vanhoutte, Roeland,Margamuljana, Lia,Nguyen, Hoai,Abu El-Asrar, Rania,Rozenski, Jef,Herdewijn, Piet,De Jonghe, Steven,Lescrinier, Eveline
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p. 645 - 662
(2019/02/25)
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- Use of substituted chromans, some of which are known, as medicaments, new active compounds and processes for their preparation
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The present invention relates to the use of substituted chromans of the general formula (I) STR1 in which the substituents have the meaning indicated in the description, for the production of medicaments, in particular as HIV protease-inhibiting agents, n
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- Indolylalkylpiperidines
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1-(Indolyl-3-alkyl)-3 or 4-(ureido or guanidino)-piperidines, e.g. those of the formula STR1 R= H; alkyl; free, etherified or esterified OH or SH; CF3, NO2 or NH2 m= 1-4; n= 2 or 3; X= O, S or NH acyl derivatives and salts thereof are antihypertensive agents.
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