- Discovery of an Ultra-rapid and Sensitive Lysosomal Fluorescence Lipophagy Process
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Non-invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non-ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q-P-ARh dye, developed by us for the first time, can stain lysosomes at ultra-low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti-interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments.
- Chen, Shan-Yong,Choe, Youmi,Kim, Jong Seung,Li, Kun,Liu, Xin,Liu, Xin-Yao,Liu, Yan-Hong,Liu, Yan-Zhao,Shi, Lei,Won, Miae,Yu, Kang-Kang,Yu, Xiao-Qi,Zhang, Hong
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supporting information
(2022/01/19)
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- Concerning the preparation of 6-bromotryptamine
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Most of the previous syntheses of the marine natural product 6-bromotryptamine have almost certainly led to partial debromination resulting in an impure product containing tryptamine. We show that loss of bromine occurs when lithium aluminum hydride is employed as a reducing agent in the final reaction step leading to 6-bromotryptamine. Reductive-debromination is also likely to intrude during some of the syntheses of 6-bromoindole, the typical precursor to 6-bromotryptamine. None of the seven described syntheses of 6-bromotryptamine that involve a reduction sequence from 6-bromoindole have reported elemental analyses as a measure of purity.
- Scott Wiens,Johnson, Jerry L.,Gribble, Gordon W.
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- NERVE-SPECIFIC FLUOROPHORE FORMULATIONS FOR DIRECT AND SYSTEMIC ADMINISTRATION
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Nerve-specific fluorophore formulations for direct or systemic administration are described. The formulations can be used in fluorescence-guided surgery (FGS) to aid in nerve preservation during surgical interventions.
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Paragraph 0342; 0344
(2020/03/02)
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- NEAR-INFRARED NERVE-SPARING FLUOROPHORES
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Provided are far red to near-infrared nerve-sparing fluorescent compounds, compositions comprising them, and methods of their use in medical procedures.
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Page/Page column 101; 102
(2020/02/17)
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- RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
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Paragraph 0316; 0317
(2019/01/11)
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- RORγ MODULATORS
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The invention provides an RORγ receptor agonist comprising a compound of formula (I), wherein the variables are as defined herein. These compounds are analogous to known RORγ receptor antagonists. The invention further provides a method of activating -the nuclear receptor RORγ, comprising -contacting the RORγ with an effective amount or concentration of a compound of the invention; and a method of treating cancer in a patient, comprising administering to the patient an effective dose of a compound of the invention.
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Page/Page column 22; 43-44; 49
(2018/04/13)
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- Sustainable Radical Cascades to Synthesize Difluoroalkylated Pyrrolo[1,2-a]indoles
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We disclose herein a photocatalytic difluoroalkylation and cyclization cascade reaction of N-(but-2-enoyl)indoles with broad substrate scopes in up to 90% isolated yield. This method provides sustainable and efficient access to synthesize difluoroalkylated pyrrolo[1,2-a]indoles with a quaternary carbon center under mild conditions.
- Huang, Honggui,Yu, Menglin,Su, Xiaolong,Guo, Peng,Zhao, Jia,Zhou, Jiabing,Li, Yi
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p. 2425 - 2437
(2018/02/23)
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- Ru(ii)-Catalyzed C7-acyloxylation of indolines with carboxylic acids
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Ruthenium(ii)-catalyzed site-selective C7-acyloxylation of indolines with carboxylic acids is presented. The substrate scope and functional group tolerance are important practical features. The kinetic isotope studies suggest that C-H bond activation may be the rate-determining step.
- De, Pinaki Bhusan,Banerjee, Sonbidya,Pradhan, Sourav,Punniyamurthy, Tharmalingam
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p. 5889 - 5898
(2018/08/21)
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- Expedient cobalt(II)-catalyzed site-selective C7-arylation of indolines with arylboronic acids
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Cobalt(ii)-catalyzed pyrimidyl directing group-assisted C7 arylation of indolines with arylboronic acids has been developed using Mn(OAc)2·4H2O as an oxidant. The use of cobalt(ii)-PCy3 as a catalyst and broad substrate scope are the important practical features.
- De, Pinaki Bhusan,Pradhan, Sourav,Banerjee, Sonbidya,Punniyamurthy, Tharmalingam
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supporting information
p. 2494 - 2497
(2018/03/21)
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- Indoline derivative and application of indoline derivative in medicine
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The invention discloses an indoline derivative, or stereisomer, tautomer, nitric oxide, solvate, metabolite, pharmacy-acceptable salt or other prodrugs of the indoline derivative. The indoline derivative is used for resisting 5-HT6 receptors. The invention further relates to a method for preparing the compound and application of the compound in treating or preventing diseases related to 5-HT6 receptors.
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Paragraph 0194; 0195; 0196; 0197; 0427; 0428; 0429; 0430
(2016/10/08)
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- N-Arylsulfonyl Indolines as Retinoic Acid Receptor-Related Orphan Receptor γ (RORγ) Agonists
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The nuclear retinoic acid receptor-related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (TH17) cell proliferation. As such, synthetic small-molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing TH17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy. Herein we describe the development of N-arylsulfonyl indolines as RORγ agonists. Structure–activity studies reveal a critical linker region in these molecules as the major determinant for agonism. Hydrogen/deuterium exchange coupled to mass spectrometry (HDX-MS) analysis of RORγ–ligand complexes help rationalize the observed results.
- Doebelin, Christelle,Patouret, Rémi,Garcia-Ordonez, Ruben D.,Chang, Mi Ra,Dharmarajan, Venkatasubramanian,Kuruvilla, Dana S.,Novick, Scott J.,Lin, Li,Cameron, Michael D.,Griffin, Patrick R.,Kamenecka, Theodore M.
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supporting information
p. 2607 - 2620
(2016/12/09)
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- SUBSTITUTED POLYCYCLIC ANTIBACTERIAL COMPOUNDS
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The present description relates to substituted polycyclic compounds of Formula (I), Formula (II) or Formula (III): wherein the dashed line represents an optional double bond and Rl, R2, R4, R5, R7, X and Z are as defined herein, and forms and compositions thereof, and also relates to uses of a compound of Formula (I), Formula (II) or Formula (III) or a form thereof and methods for treating or ameliorating Neisseria gonorrhoeae (N. gonorrhoeae) in a subject in need thereof comprising, administering an effective amount of the compound to the subject.
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Page/Page column 144
(2016/02/29)
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- A divergent SAR study allows optimization of a potent 5-HT2c inhibitor to a promising antimalarial scaffold
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From the 13-533 chemical structures published by GlaxoSmithKline in 2010, we identified 47 quality starting points for lead optimization. One of the most promising hits was the TCMDC-139046, a molecule presenting an indoline core, which is well-known for its anxiolytic properties by interacting with serotonin antagonist receptors 5-HT2. The inhibition of this target will complicate the clinical development of these compounds as antimalarials. Herein, we present the antimalarial profile of this series and our efforts to avoid interaction with this receptor, while maintaining a good antiparasitic potency. By using a double-divergent structure-activity relationship analysis, we have obtained a novel lead compound harboring an indoline core.
- Calderon, Felix,Vidal-Mas, Jaume,Burrows, Jeremy,De La Rosa, Juan Carlos,Jimenez-Diaz, Maria Belen,Mulet, Teresa,Prats, Sara,Solana, Jorge,Witty, Michael,Gamo, Francisco Javier,Fernandez, Esther
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supporting information; experimental part
p. 373 - 377
(2012/06/30)
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- FUSED HETEROCYCLIC C-GLYCOSIDES FOR THE TREATMENT OF DIABETES
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The present invention provides compounds of Formula (IA) wherein A is selected from Formula (II) which have an inhibitory effect on the sodium dependent glucose transporter SGLT and their use in the treatment of diabetes.
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Page/Page column 106-107
(2010/11/18)
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- Indoles
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A 1,4-substituted cyclic amine derivative represented by the following formula or a pharmacologically acceptable salt thereof: wherein A, B, C, D, T, Y, and Z each represent a methine or a nitrogen linkage; R1, R2, R3, R4, and R5 each represent a substituent; n represents 0 or an integer of 1 to 3; m represents 0 or an integer of 1 to 6; and p represents an integer of 1 to 3. The compounds have serotonin antagonism. They are therefore clinically useful as medicaments, in particular, for treating, ameliorating, and preventing spastic paralysis. They are also useful as central muscle relaxants for ameliorating myotonia.
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- Synthesis of 6-Methoxyindoles and Indolines. Regioselective C-6 Bromination of Indolines and Subsequent Nucleophilic Substitution with a Methoxyl Group
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Regioselective bromination of the 6-position of indolines was investigated.Treatment of indolines with bromine in sulfuric acid in the presence of silver sulfate or with bromine in superacid afforded the 6-bromoindolines, which were converted to 6-methoxyindolines and indoles.
- Miyake, Yuko,Kikugawa, Yasuo
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p. 349 - 352
(2007/10/02)
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