- Design, synthesis and SAR of antitubercular benzylpiperazine ureas
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Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]
- Satish, Sohal,Chitral, Rohan,Kori, Amitkumar,Sharma, Basantkumar,Puttur, Jayashree,Khan, Afreen A.,Desle, Deepali,Raikuvar, Kavita,Korkegian, Aaron,Martis, Elvis A. F.,Iyer, Krishna R.,Coutinho, Evans C.,Parish, Tanya,Nandan, Santosh
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- Synthesis of β-Diamine Building Blocks by Photocatalytic Hydroamination of Enecarbamates with Amines, Ammonia and N?H Heterocycles
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3-Amino-substituted saturated nitrogen heterocycles are an important subclass of β-diamines, appearing in a number of clinical agents. Herein, we report a unified approach to these products based upon the regioselective photoredox-mediated hydroamination of enecarbamates. The amine coupling partner can encompass diverse amine types under a single set of reaction conditions, including primary alkyl amines, ammonia, aryl and heteroaryl amines, and N?H heterocycles. The method enables the synthesis of a wide range of pharmaceutically relevant building blocks.
- Francis, Daniel,Nelson, Adam,Marsden, Stephen P.
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supporting information
p. 14861 - 14865
(2020/10/12)
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- AMIDE DERIVATIVE
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The present invention relates to a compound of the formula (I) being useful as a renin inhibitor, or a pharmaceutically acceptable salt thereof. wherein R1a is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.; R1b is an optionally substituted C1-6 alkoxy, etc.; R1c is a hydrogen atom, an optionally substituted C1-6 alkoxy, etc.; R2 is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.; R3a, R3b, R3c and R3d are independently the same or different, and each is a group of the formula: -A-B (in which A is a single bond, -(CH2)sO-, - (CH2)sN(R4)CO-, etc., B is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.), etc.; R4 is a hydrogen atom, an optionally substituted C1-6 alkyl, etc.; s is 0, etc.; and n is 1, etc.
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Page/Page column 112
(2009/12/05)
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- Naphthyridine antibacterial agents containing an α-amino acid in the side chain of the 7-substituent
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Novel quinolone and naphthyridine antibacterial agents are herein described having improved in vivo activity both orally and subcutaneously where the 7-side chain of such compounds contain an α-amino acid; also described are its corresponding optical isomers, methods of preparation as well as compositions and methods of treating infections diseases.
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