15050-24-5Relevant articles and documents
Macrocyclic squaramides as ion pair receptors and fluorescent sensors selective towards sulfates
Zaleskaya, Marta,Jagleniec, Damian,Romański, Jan
, p. 3904 - 3915 (2021)
Through the high dilution technique, we obtained macrocyclic ion pair receptorsR1andR2, an anion receptorR3, and a fluorescent sensorR4using a combination of particular members of simple libraries consisting of synthesized diamines and methyl squarates, r
Atropisomerism in azadipeptides: evaluation of N1-methylation and thioamide introduction
Ottersbach, Philipp A.,Schnakenburg, Gregor,Gütschow, Michael
, p. 4889 - 4891 (2015)
Abstract Cbz-protected azadipeptides, designed as structurally reduced model compounds, were synthesized and investigated with respect to the occurrence of atropisomerism. Methylation at the carbamate nitrogen caused mixtures of E and Z isomers in Cbz-sar
Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-xL Antagonist. 1. Manufacture of the Acid Moiety and Development of Some Key Reactions
Hardouin, Christophe,Baillard, Sandrine,Barière, Fran?ois,Copin, Chloé,Craquelin, Anthony,Janvier, Solenn,Lemaitre, Sylvain,Le Roux, Stéphane,Russo, Olivier,Samson, Sébastien
, p. 652 - 669 (2019/12/24)
Our efforts toward the process development of drug candidate 1 are described in a series of two papers. This manuscript focuses on the synthesis of kilogram quantities of acid precursor 2 to provide batches of material for preclinical studies and first-in
Identification of Small-Molecule Modulators of Diguanylate Cyclase by FRET-Based High-Throughput Screening
Christen, Matthias,Kamischke, Cassandra,Kulasekara, Hemantha D.,Olivas, Kathleen C.,Kulasekara, Bridget R.,Christen, Beat,Kline, Toni,Miller, Samuel I.
, p. 394 - 407 (2019/01/04)
The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) is a key regulator of cellular motility, the cell cycle, and biofilm formation with its resultant antibiotic tolerance, which can make chronic infections difficult to treat. Therefore, diguanylate cyclases, which regulate the spatiotemporal production of c-di-GMP, might be attractive drug targets for control of biofilm formation that is part of chronic infections. We present a FRET-based biochemical high-throughput screening approach coupled with detailed structure–activity studies to identify synthetic small-molecule modulators of the diguanylate cyclase DgcA from Caulobacter crescentus. We identified a set of seven small molecules that regulate DgcA enzymatic activity in the low-micromolar range. Subsequent structure–activity studies on selected scaffolds revealed a remarkable diversity of modulatory behavior, including slight chemical substitutions that reverse the effects from allosteric enzyme inhibition to activation. The compounds identified represent new chemotypes and are potentially developable into chemical genetic tools for the dissection of c-di-GMP signaling networks and alteration of c-di-GMP-associated phenotypes. In sum, our studies underline the importance of detailed mechanism-of-action studies for inhibitors of c-di-GMP signaling and demonstrate the complex interplay between synthetic small molecules and the regulatory mechanisms that control the activity of diguanylate cyclases.
Hybrids of arenobufagin and benzoisoselenazol reducing the cardiotoxicity of arenobufagin
Hou, Wen,Huang, Zhi-Xing,Xu, Hong-Gui,Lin, Jing,Zhang, Dong-Mei,Peng, Qun-Long,Lin, Hui,Chang, Yi-Qun,Wang, Long-Hai,Yao, Zhe,Sun, Ping-Hua,Chen, Wei-Min
, p. 3391 - 3394 (2018/09/11)
Arenobufagin is a naturally occurring bufadienolide showing promising antitumor activity accompanied however with apparent cardiac toxicity. Following the recent discovery that oxidative damage possibly be an important cause of the cardiac toxicity of cardenolides, a strategy fusing the antitumor agent arenobufagin with a benzoisoselenazol fragment, a reactive oxygen species (ROS) scavenger, has been developed. Six novel hybrids were synthesized and their ROS scavenging activities as well as their in vitro cytotoxicity against the human hepatocellular carcinoma cell line HepG2, an adriamycin-resistant subline HepG2/ADM, and the human myocardial cell line AC16 were evaluated. The results indicate that the hybrids exhibit various degrees of in vitro ROS scavenging activities, and weaker cytotoxicity than that of arenobufagin against the myocardial cell line AC16. These findings suggest the feasibility of a strategy in which the cardiotoxicity of the potential antitumor agent arenobufagin is reduced.
The synthesis of Nα-protected amino hydroxamic acids from Nα-protected amino acids employing versatile chlorinating agent CPI-Cl
Vathsala,Srinivasulu,Santhosh,Sureshbabu, Vommina V.
, p. 449 - 457 (2019/03/08)
Racemization free synthesis of Nα-protected amino hydroxamic acids from Nα-protected amino acids employing the versatile chlorinating reagent CPI-Cl has been described in one-pot. The present protocol has shown compability towards urethane protecting groups like Boc, Cbz and Fmoc, and side chain protections of amino acids showed complete tolerance.
THERAPEUTIC COMPOUNDS AND FORMULATIONS FOR INTRANASAL DELIVERY
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Page/Page column 28-29, (2016/10/24)
Certain embodiments of the invention provide a formulation suitable for nasal administration comprising water, a prodrug of a therapeutic agent, and an enzyme that is suitable for intranasal conversion of the prodrug to the therapeutic agent, as well as methods of use thereof.
PERIPHERALLY RESTRICTED GABA POSITIVE ALLOSTERIC MODULATORS FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME AND OTHER AILMENTS OF THE PERIPHERAL NERVOUS SYSTEM
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Paragraph 0120-0121, (2016/01/12)
The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.
Pyrrolopyrimidine-inhibitors with hydantoin moiety as spacer can explore P4/S4 interaction on plasmin
Teno, Naoki,Gohda, Keigo,Wanaka, Keiko,Tsuda, Yuko,Sueda, Takuya,Yamashita, Yukiko,Otsubo, Tadamune
supporting information, p. 2339 - 2352 (2014/04/17)
In the development of plasmin inhibitors, a novel chemotype, pyrrolopyrimidine scaffold possessing two motifs, a hydantoin-containing P4 moiety and a warhead-containing P1 moiety, is uncovered. A unique feature of the new line of the plasmin inhibitors is
Structural optimization of azadipeptide nitriles strongly increases association rates and allows the development of selective cathepsin inhibitors
Frizler, Maxim,Lohr, Friederike,Furtmann, Norbert,Kl?s, Julia,Gütschow, Michael
supporting information; experimental part, p. 396 - 400 (2011/03/18)
Using the example of cathepsin K, we demonstrate the design of highly potent and selective azadipeptide nitrile inhibitors. A systematic scan with respect to P2 and P3 substituents was carried out. Structural modifications strongly affected the enzyme-inh
