59862-83-8Relevant articles and documents
In Vivo Half-Life Extension of BMP1/TLL Metalloproteinase Inhibitors Using Small-Molecule Human Serum Albumin Binders
Vantourout, Julien C.,Mason, Andrew M.,Yuen, Josephine,Simpson, Graham L.,Evindar, Ghotas,Kuai, Letian,Hobbs, Michael,Edgar, Emma,Needle, Saul,Bai, Xiaopeng,Wilson, Steve,Scott-Stevens, Paul,Traylen, William,Lambert, Kim,Young, Neil,Bunally, Shenaz,Summerfield, Scott G.,Snell, Richard,Lad, Rakesh,Shi, Eric,Skinner, Steven,Shewchuk, Lisa,Watson, Allan J.B.,Chung, Chun-Wa,Pal, Sandeep,Holt, Dennis A.,Kallander, Lara S.,Prendergast, Joanne,Rivera, Katrina,Washburn, David G.,Harpel, Mark R.,Arico-Muendel, Christopher,Isidro-Llobet, Albert
, p. 279 - 289 (2021)
Reducing the required frequence of drug dosing can improve the adherence of patients to chronic treatments. Hence, drugs with longer in vivo half-lives are highly desirable. One of the most promising approaches to extend the in vivo half-life of drugs is conjugation to human serum albumin (HSA). In this work, we describe the use of AlbuBinder 1, a small-molecule noncovalent HSA binder, to extend the in vivo half-life and pharmacology of small-molecule BMP1/TLL inhibitors in humanized mice (HSA KI/KI). A series of conjugates of AlbuBinder 1 with BMP1/TLL inhibitors were prepared. In particular, conjugate c showed good solubility and a half-life extension of >20-fold versus the parent molecule in the HSA KI/KI mice, reaching half-lives of >48 h with maintained maximal inhibition of plasma BMP1/TLL. The same conjugate showed a half-life of only 3 h in the wild-type mice, suggesting that the half-life extension was principally due to specific interactions with HSA. It is envisioned that conjugation to AlbuBinder 1 should be applicable to a wide range of small molecule or peptide drugs with short half-lives. In this context, AlbuBinders represent a viable alternative to existing half-life extension technologies.
Method for preparing 2,5-furandicarboxylic acid
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, (2017/08/29)
The invention discloses a method for preparing 2,5-furandicarboxylic acid. The method comprises the following steps: preparing the 2,5-furandicarboxylic acid by sequentially performing four-step reaction namely bromination reaction, esterification reaction, carbonylation reaction and hydrolysis reaction on furan-2-carboxylic acid, wherein a compound as shown in Formula 3, a compound as shown in Formula 4 and a compound as shown in Formula 5 are obtained by the bromination reaction, the esterification reaction and the carbonylation reaction respectively. Compared with the prior art, the invention can effectively solve the problem of not high yield or severe reaction condition requirement by improving the key overall process flow of the preparation method and reaction conditions of each step. The structural formulae of the compound as shown in Formula 3, the compound as shown in Formula 4 and the compound as shown in Formula 5 are as shown in the specification respectively.
[2+2+2] Cycloadditions of alkynylynamides - A total synthesis of perlolyrine and the first total synthesis of "isoperlolyrine"
Dassonneville, Benjamin,Witulski, Bernhard,Detert, Heiner
experimental part, p. 2836 - 2844 (2011/06/23)
The total syntheses of the carboline alkaloids perlolyrine and "isoperlolyrine" are reported. Key-steps of the syntheses are Negishi coupling reactions on alkynylynamides and their metal-catalyzed [2+2+2] cycloadditions with nitriles to form the β- and γ-
