45804-94-2Relevant articles and documents
Multienzymatic preparation of (-)-[3-(oxiran-2-yl)phenyl]methanol and (-)-3-(oxiran-2-yl)benzoic acid
Sello, Guido,Bernasconi, Silvana,Orsini, Fulvia,Di Gennaro, Patrizia
, p. 563 - 565 (2009)
The cascade use of enzymatic activities allows for the preparation of enantiomerically pure epoxides. In particular, using whole-cell biocatalysts we can prepare both (-)-[3-(oxiran-2-yl)phenyl]methanol and (-)-3-(oxiran-2-yl)benzoic acid in one-pot, two
MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X4 AND RELATED PRODUCTS AND METHODS
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Page/Page column 247-248, (2020/10/18)
Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein n, x, A, Q1, Q2, Z, R, R1, R2, R3, R4 and R5 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided.
Discovery of Potent Cyclophilin Inhibitors Based on the Structural Simplification of Sanglifehrin A
Steadman, Victoria A.,Pettit, Simon B.,Poullennec, Karine G.,Lazarides, Linos,Keats, Andrew J.,Dean, David K.,Stanway, Steven J.,Austin, Carol A.,Sanvoisin, Jonathan A.,Watt, Gregory M.,Fliri, Hans G.,Liclican, Albert C.,Jin, Debi,Wong, Melanie H.,Leavitt, Stephanie A.,Lee, Yu-Jen,Tian, Yang,Frey, Christian R.,Appleby, Todd C.,Schmitz, Uli,Jansa, Petr,Mackman, Richard L.,Schultz, Brian E.
, p. 1000 - 1017 (2017/02/19)
Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but the generation of potent, drug-like molecules through chemical synthesis has been challenging. In this study, a set of macrocyclic cyclophilin inhibitors was synthesized based on the core structure of the natural product sanglifehrin A. Initial compound optimization identified the valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in the sanglifehrin core, stereocenters at C14 and C15, and the hydroxyl group of the m-tyrosine (m-Tyr) residue as key contributors to compound potency. Replacing the C18-C21 diene unit of sanglifehrin with a styryl group led to potent compounds that displayed a novel binding mode in which the styrene moiety engaged in a π-stacking interaction with Arg55 of cyclophilin A (Cyp A), and the m-Tyr residue was displaced into solvent. This observation allowed further simplifications of the scaffold to generate new lead compounds in the search for orally bioavailable cyclophilin inhibitors.
