- Design of tRNALys3 Ligands: Fragment evolution and linker selection guided by NMR spectroscopy
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A fragment-based approach for the synthesis of ligands of tRNA Lys3, the HIV reverse-transcription primer, is described. The use of NMR spectroscopy has proved to be very useful in this approach, not only to detect lowaffinity complexes between small compounds and RNA, but also to provide information on their binding mode and on the way they can be connected. This NMR-spectroscopy-guided analysis enabled us to design micromolar ligands after the optimisation and connection of millimolar fragments with an appropriate linker. The influence of the linker region on the binding affinity and selectivity outlines the importance of having a flexible assemblage strategy with a variety of linkers in such an approach. 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
- Chung, Florence,Tisne, Carine,Lecourt, Thomas,Seijo, Bili,Dardel, Frederic,Micouin, Laurent
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- NMR-guided fragment-based approach for the design of tRNALys3 ligands
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Two in one: Two ligands for tRNALys3 that were identified from a compound library by flow-injection NMR spectroscopic screening and found to have millimolar dissociation constants (on the left in the picture) inspired the fragment-based synthesis of a new family of ligands with the general structural features of both initial compounds. Ligand 1 of this family is a selective D-stem binder of tRNALys3 with a micromolar Kd value.
- Chung, Florence,Tisne, Carine,Lecourt, Thomas,Dardel, Frederic,Micouin, Laurent
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Read Online
- Metal-free synthesis of β-aminoketones by the reductive hydroamination of ynones
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This study describes a cascade method for the synthesis of β-aminoketones through the reductive hydroamination of alkynes under very mild metal-free conditions. It allows for the rapid conversion of ynones and amines into corresponding β-aminoketones with a broad substrate scope and diverse functionalities. This straightforward and easy-to-handle reaction process can be successfully applied for the synthesis of Proroxan and Propipocaine, offering a potential option for the synthesis of drug molecules with the β-aminoketone skeleton.
- Fu, Rui,Liu, Yu,Wu, Tao,Zhang, Xinyu,Zhu, Yang,Luo, Jiangbin,Zhang, Zhengyu,Jiang, Yaojia
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p. 3525 - 3528
(2022/03/31)
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- GAMMA-DIKETONES AS WNT/BETA -CATENIN SIGNALING PATHWAY ACTIVATORS
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The present disclosure provides γ-diketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries or spine injuries, brain atrophy/neurological disorders related to the differentiation and development of the central nervous system, including Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; otic disorders like cochlear hair cell loss; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, such as hair loss, hematopoiesis related diseases and tissue regeneration related diseases.
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Paragraph 1714; 1715; 1716; 1730
(2014/09/03)
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- ARALKYL DIAMINE DERIVATIVES AND USES THEREOF AS ANTIDEPRESSANT
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Aralkyl diamine derivative of the following formula, pharmaceutically acceptable salts or uses thereof as antidepressants. The derivatives have triplex inhibiting activities of the reuptake of 5-HT, dopamine and noradrenalin, which can be administered to the patients in need of such treatment in the form of compositions orally or injectedly et al.
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Paragraph 0030; 0160
(2013/03/28)
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- AMINE COMPOUNDS AND THEIR PHARMACEUTICAL USE
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The present invention relates to a new amine compound or a pharmaceutically acceptable salt thereof, wherein the definitions of X, R1, R2 and n are given in the description, to a pharmaceutical composition containing the compound as active ingredient, and to use of the amine compound or its pharmaceutically acceptable salt for the manufacture of an anti-depressent drug.
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- Synthesis of 2,6-diaryl-substituted pyridines and their antitumor activities
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For the development of novel antitumor agents, we designed and synthesized 2,6-diaryl-substituted pyridine derivatives bearing three aryl groups, which are the bioisosteres of terpyridine, and evaluated their biological activities. Most of the 18 prepared compounds showed moderate cytotoxicity against several human cancer cell lines. From the structure-activity relationships we may conclude that the number of aryl groups employed would be critical for their biological activities.
- Son, Jong-Keun,Zhao, Long-Xuan,Basnet, Arjun,Thapa, Pritam,Karki, Radha,Na, Younghwa,Jahng, Yurngdong,Jeong, Tae Cheon,Jeong, Byeong-Seon,Lee, Chong-Soon,Lee, Eung-Seok
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p. 675 - 682
(2008/09/20)
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- A process for the preparation of an intermediate useful for the asymmetric synthesis of (+)duloxetine
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A process for the preparation of (+)duloxetine, or an acid addition salt thereof, comprising: (i) Resolving racemic (±)N-methyl duloxetine with a less than stoichiometric amount of a chiral acid in combination with suitable amounts of a hydrohalogen acid to give a salt of the chiral acid and (+)N-methyl duloxetine, substantially free from (-)N-methyl duloxetine; (ii) Demethylating the (+)N-methyl duloxetine prepared in step (i) to give (+)duloxetine or another acid addition salt in enantiomerically pure form.
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Page/Page column 4
(2010/11/28)
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- 3-METHYLAMINO-1-(2-THIENYL)-1-PROPANONE, PRODUCTION AND USE THEREOF
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The invention relates to the production of 3-methylamino-1-(2-thienyl)-1-propanone and the use thereof for producing the pharmaceutical (+)-(S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine oxalate (trade name Duloxetine?).
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Page/Page column 6
(2008/06/13)
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- Further exploration of 1-{2-[Bis-(4-fluorophenyl)methoxy]ethyl}piperazine (GBR 12909): Role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter
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A series of N-aromatic, N-heteroaromatic, and oxygenated N-phenylpropyl derivatives of 1-(2-benzhydryloxyethyl)-piperazine and 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}piperazine, analogues of GBR 12909 (1a) and 12935 (1b), was synthesized and examined for their dopamine (DAT) and serotonin (SERT) transporter binding properties. One of these compounds, racemic 3-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-1-(3-fluorophenyl)-propan-1-ol (33), had DAT affinity as good as, or better than, GBR 12909 and 12935, and was more selective for DAT over SERT than the GBR compounds. Both trans- (43) and cis- (47) (±)-2-(4-{2-[bis-(4-fluorophenyl)-methoxy]ethyl}piperazin-1- ylmethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol had relatively good SERT selectivity and, as well, showed high affinity for SERT.
- Lewis, David,Zhang, Ying,Prisinzano, Thomas,Dersch, Christina M.,Rothman, Richard B.,Jacobson, Arthur E.,Rice, Kenner C.
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p. 1385 - 1389
(2007/10/03)
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- Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake.
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A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta) has proven to be effective in clinical trials for the treatment of depression.
- Bymaster,Beedle,Findlay,Gallagher,Krushinski,Mitchell,Robertson,Thompson,Wallace,Wong
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p. 4477 - 4480
(2007/10/03)
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- Synthesis of some new thienyl and 1,3-thiazolyl-aminoketones with anti- inflammatory activity
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Eight thienyl and 1,3-thiazolyl-aminoketones were synthesised and tested as anti-inflammatory agents, pKa and log P were theoretically calculated. The compounds were tested for antioxidant activity, as hydroxyl radical scavengers, as superoxide anion scavengers and for their ability to interact with 1,1-diphenyl-2-picryl hydrazyl stable free radical (DPPH. The effects of the synthesised compounds on inflammation were studied using the carrageenan induced mice paw oedema model. Both anti-inflammatory and antioxidant activities depended on some structural characteristics of the synthesised compounds.
- Geronikaki, Athina A.,Hadjipavlou-Litina, Dimitra J.,Tzaki, Maria
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p. 266 - 271
(2007/10/03)
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- Chiral synthesis of 1-aryl-3-aminopropan-1-ols
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This invention is directed to a process for preparing chiral 1-aryl-3-amino-propan-1-ols. These compounds are important intermediates in the synthesis of pharmacologically active compounds.
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