19461-04-2Relevant academic research and scientific papers
A Phenylalanine Derivative Containing a 4-Pyridine Group Can Construct Both Single Crystals and a Selective Cu-Ag Bimetallohydrogel
Wei, Chuan-Wan,Wang, Xiao-Juan,Gao, Shu-Qin,Wen, Ge-Bo,Lin, Ying-Wu
supporting information, p. 1349 - 1353 (2019/02/14)
Metallohydrogels are attractive biomaterials, whereas formation of a selective bimetallogel in aqueous solution has rarely been explored. In this study, we show that a phenylalanine derivative containing a 4-pyridine group can not only assemble to form si
Biocatalytic Synthesis of Chiral N-Functionalized Amino Acids
Hyslop, Julia F.,Lovelock, Sarah L.,Sutton, Peter W.,Brown, Kristin K.,Watson, Allan J. B.,Roiban, Gheorghe-Doru
supporting information, p. 13821 - 13824 (2018/09/27)
N-Functionalized amino acids are important building blocks for the preparation of diverse bioactive molecules, including peptides. The development of sustainable manufacturing routes to chiral N-alkylated amino acids remains a significant challenge in the pharmaceutical and fine-chemical industries. Herein we report the discovery of a structurally diverse panel of biocatalysts which catalyze the asymmetric synthesis of N-alkyl amino acids through the reductive coupling of ketones and amines. Reactions have been performed on a gram scale to yield optically pure N-alkyl-functionalized products in high yields.
Discovery of novel 20S proteasome inhibitors by rational topology-based scaffold hopping of bortezomib
Xu, Yulong,Yang, Xicheng,Chen, Yiyi,Chen, Hao,Sun, Huijiao,Li, Wei,Xie, Qiong,Yu, Linqian,Shao, Liming
supporting information, p. 2148 - 2152 (2018/05/25)
A series of structurally novel proteasome inhibitors 1–12 have been developed based rational topology-based scaffold hopping of bortezomib. Among these novel proteasome inhibitors, compound 10 represents an important advance due to the comparable proteasome-inhibitory activity (IC50 = 9.7 nM) to bortezomib (IC50 = 8.3 nM), the remarkably higher BEI and SEI values and the effectiveness in metabolic stability. Therefore, compound 10 provides an excellent lead suitable for further optimization.
Tuning of protease resistance in oligopeptides through: N -alkylation
Kaminker, Revital,Anastasaki, Athina,Gutekunst, Will R.,Luo, Yingdong,Lee, Sang-Ho,Hawker, Craig J.
supporting information, p. 9631 - 9634 (2018/09/10)
N-Methylation of amino acids is an effective way to create protease resistance in both natural and synthetic peptides. However, alkyl substituents other than N-methyl have not been extensively studied. Here, we prepare and examine a series of N-substituted peptides in which the size and length of the alkyl group is modulated. These design insights provide a unique and modular handle for tuning proteolysis in oligopeptides.
Boric acid compound used as 20S proteasome inhibitor, and preparation method thereof
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Paragraph 0198; 0199; 0200, (2017/09/19)
The invention relates to the fields of pharmaceutical chemistry and medicine therapeutics, concretely relates to new boric acid compounds, and a preparation method and a use thereof, and especially relates to a boric acid compound used as a 20S proteasome inhibitor, and a preparation method thereof. The invention also discloses a boric acid compound represented by formula I, and a preparation method thereof. A result of bioactive screening test shows that the compound prepared in the invention has a proteasome inhibition function, and can be further used for preparing medicines for treating proteasome correlated diseases.
Aminoacid-derivatized Cu (II) complexes: Synthesis, DNA interactions and in vitro cytotoxicity
Singh, Rinky,Devi, P. Rama,Jana, Sharmita S.,Devkar, Ranjitsinh V.,Chakraborty, Debjani
, p. 157 - 169 (2017/09/30)
Two different series of copper complexes, [Cu(MFL)(FcAA)H2O] (C1-C4) and [Cu(MFL) (BzAA)H2O] (C5-C8), where FcAA = ferrocenyl amino acid mannich base conjugates and BzAA = benzaldehyde amino acid mannich base conjugates have been syn
Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
, p. 9067 - 9089 (2017/11/14)
Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
Concise, stereodivergent and highly stereoselective synthesis of cis-and trans-2-substituted 3-hydroxypiperidines-development of a phosphite-driven cyclodehydration
Huy, Peter H.,Westphal, Julia C.,Koskinen, Ari M.P.
supporting information, p. 369 - 383 (2014/03/21)
A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.
Photocytotoxic ferrocene-appended (l-tyrosine)copper(II) complexes of phenanthroline bases
Goswami, Tridib K.,Gadadhar, Sudarshan,Karande, Anjali A.,Chakravarty, Akhil R.
, p. 1287 - 1298 (2013/07/11)
Copper(II) complexes of ferrocene(Fc)-conjugated reduced Schiff base of l-tyrosine (Fc-TyrH), viz., [Cu(Fc-Tyr)(L)](ClO4), where L is 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 2), dipyrido[3,2-a:2′,3′-c]phenazine (
Efficient, stereodivergent access to 3-piperidinols by traceless P(OEt)3 cyclodehydration
Huy, Peter H.,Koskinen, Ari M. P.
, p. 5178 - 5181 (2013/11/06)
A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a "traceless" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is developed.
