- New direct inhibitors of InhA with antimycobacterial activity based on a tetrahydropyran scaffold
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Tetrahydropyran derivative 1 was discovered in a high-throughput screening campaign to find new inhibitors of mycobacterial InhA. Following initial in-vitro profiling, a structure-activity relationship study was initiated and a focused library of analogs was synthesized and evaluated. This yielded compound 42 with improved antimycobacterial activity and low cytotoxicity. Additionally, the crystal structure of InhA in complex with inhibitor 1 was resolved, to reveal the binding mode and provide hints for further optimization.
- Pajk, Stane,?ivec, Matej,?ink, Roman,Sosi?, Izidor,Neu, Margarete,Chung, Chun-Wa,Martínez-Hoyos, María,Pérez-Herrán, Esther,álvarez-Gómez, Daniel,álvarez-Ruíz, Emilio,Mendoza-Losana, Alfonso,Castro-Pichel, Julia,Barros, David,Ballell-Pages, Lluís,Young, Robert J.,Convery, Maire A.,Encinas, Lourdes,Gobec, Stanislav
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supporting information
p. 252 - 257
(2016/05/02)
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- COMPOUNDS AND METHODS for the inhibition of HDAC
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Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, Z, L and n are as defined herein, and methods of making and using the same.
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Paragraph 0132-0133
(2015/11/24)
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- COMPOUNDS AND METHODS
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Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, n and L are as defined herein, and methods of making and using the same.
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Page/Page column 37
(2011/08/04)
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