45270-18-6Relevant articles and documents
Synthesis and functional analysis of novel bivalent estrogens
Wendlandt, Alison E.,Yelton, Sharon M.,Lou, Dingyuan,Watt, David S.,Noonan, Daniel J.
, p. 825 - 833 (2010)
The steroid hormone estrogen plays a critical role in female development and homeostasis. Estrogen mediates its effects through binding and activation of specific estrogen receptors alpha (ERα) and beta (ERβ), members of the steroid/nuclear receptor family of ligand-induced transcription factors. Due to their intimate roles in genomic and nongenomic signaling pathways, these hormones and their receptors have been also implicated in the pathologies of a variety of cancers and metabolic disorders, and have been the target of large therapeutic development efforts. The binding of estrogen to its respective receptors initiates a cascade of events that include receptor dimerization, nuclear localization, DNA binding and recruitment of co-regulatory protein complexes. In this manuscript, we investigate the potential for manipulating steroid receptor gene expression activity through the development of bivalent steroid hormones that are predicted to facilitate hormone receptor dimerization events. Data are presented for the development and testing of novel estrogen dimers, linked through their C-17 moiety, that can activate estrogen receptor alpha (ERα)-mediated transcription events with efficacy and potency equal to or greater than that of ERα's cognate ligand, 17β-estradiol. These bivalent estrogen structures open the door to the development of a variety of steroid therapeutics that could dramatically impact future drug development in this area.
A process for preparing a fatty acid derivative method and its application (by machine translation)
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Paragraph 0133-0136, (2018/04/01)
The invention discloses a method for preparing a fatty acid derivative method and its application. The first method is the long-chain fatty acid and thionyl chloride reaction, to obtain the acyl chloride; acyl chloride of preparing butanol reaction, then remove chlorine group, and get long-chain fatty acid uncle ding zhi; then and N - hydroxysuccinimide reaction, long-chain fatty acid succinimide and high yield butylacrylate; then with the L - glutamic acid - 1 - tert-butyl reaction, to obtain tert-butyl long-chain fatty acyl - L - Glu - OtBu; with the N - hydroxysuccinimide reaction, to obtain tert-butyl long-chain fatty acyl - L - Glu (OSu)- OtBu; finally [...] butyl long-chain fatty acyl - L - Glu (OSu)- OtBu tert-butyl in removing, and get long-chain fatty acid derivatives. The method routes the operation is simple, quality is controllable, is suitable for industrial production, and low cost, simple purification at the same time, suitable for use in the preparation of high purity insulin analogs. (by machine translation)
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D2-like receptors
Salama, Ismail,L?ber, Stefan,Hübner, Harald,Gmeiner, Peter
supporting information, p. 3753 - 3756 (2014/09/16)
Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites.
One-pot synthesis of permethylated α-CD-based rotaxanes having alkylene chain axles and their structural characteristics
Akae, Yosuke,Arai, Takayuki,Koyama, Yasuhito,Okamura, Hisashi,Johmoto, Kohei,Uekusa, Hidehiro,Kuwata, Shigeki,Takata, Toshikazu
supporting information; experimental part, p. 806 - 808 (2012/09/22)
Permethylated i-CD-based rotaxanes with short alkylene chains as an axle were synthesized through urea end-capping in one pot: Products were [2]rotaxane and [3]rotaxane. The headto-head structure of [3]rotaxane obtained as a single isomer was confirmed by the characteristic 1HNMR peak shifts and X-ray single-crystal structure analysis.
