The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.
Unusual o-alkylation with iodomethyltrimethylsilane
作者:T. K. Chakraborty、G. V. Reddy
DOI:10.1039/c39890000251
日期:——
Iodomethyltrimethylsilane alkylates alkoxide ions giving rise to O-methyl and O-trimethylsilyl ethers which are formed by cleavage of the silicon–carbon bond.
碘甲基三甲基硅烷烷基化烷氧基离子,生成O-甲基和O-三甲基甲硅烷基醚,它们是通过硅碳键断裂形成的。
Sphingosine-1-phosphate receptor agonist and antagonist compounds
申请人:Wallace Grier A.
公开号:US20090029947A1
公开(公告)日:2009-01-29
The present invention is directed to novel, potent, and selective agents, which are agonists or antagonists of the one or more of the individual receptors of the S1P receptor family. The compounds of the invention are useful as therapeutics for treating medical conditions associated with agonism or antagonism of the individual receptors of the S1P receptor family.
2-amino-thiazole derivatives, process for their preparation, and their use as antitumor agents
申请人:Pharmacia & Upjohn S.p.A.
公开号:US07037929B1
公开(公告)日:2006-05-02
Compounds which are 2-amino-1,3-thiazole derivatives of formula (I)
wherein R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group, optionally further substituted, selected from i) straight or branched C1–C8 alkyl, C2–C6 alkenyl or C2–C6 alkynyl; ii) C3–C6 cycloalkyl; iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain; R1 is an optionally further substituted group selected from: i) straight or branched C1–C8 alkyl or C2–C6 alkenyl; ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring; iii) aryl or arylcarbonyl; iv) arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain; v) arylalkenyl with from 2 to 6 carbon atoms within the straight or branched alkenyl chain; vi) an optionally protected amino acid residue; or a pharmaceutically acceptable salt thereof; are useful for treating cell proliferative disorders associated with an altered cell dependent kinase activity.
Compounds and methods for the targeted degradation of androgen receptor
申请人:Arvinas, Inc.
公开号:US11352351B2
公开(公告)日:2022-06-07
The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.