- SUBSTITUTED 3-((3-AMINOPHENYL)AMINO)PIPERIDINE-2,6-DIONE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are piperidine dione compounds having the following structure: wherein RN, R1, R2, R3, R4, X, L, V, m, and n are as defined herein, compositions comprising an effective amount of a piperidine dione compound, and methods for treating or preventing an androgen receptor mediated disease.
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Paragraph 0519; 0520
(2020/07/14)
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 558
(2020/10/21)
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- Synthesis and Antimicrobial Evaluation of Novel Chiral 2-Amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Derivatives
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New N-substituted-2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives were synthesized employing a convenient one-pot three-component method and their structures were characterized by 1H-NMR and single crystal X-ray diffraction analysis. All the synthesized compounds were in vitro screened for antimicrobial activity against Gram-positive (Sarcina lutea) and Gram-negative bacteria (Escherichia coli). In this work, we introduced a chiral residue on the tetrahydropyridine nitrogen, the hitherto the less investigated position on this pharmacophore in order to explore the effect. The antibacterial results showed that the synthesized compounds were active only against Gram-positive bacteria and the (R)-enantiomers displayed a greater antimicrobial potency than their (S)-counterparts. The structure–activity relationship here investigated may provide some interesting clues for future development of tetrahydrothienopyridine derivatives with higher antimicrobial activity.
- Rossetti, Arianna,Bono, Nina,Candiani, Gabriele,Meneghetti, Fiorella,Roda, Gabriella,Sacchetti, Alessandro
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- Protein labelling and albumin binding characteristics of the near-IR Cy7 fluorophore, QuatCy
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Free cysteine residues react with QuatCy 1, by simply mixing the protein and dye in aqueous buffer at 37 °C. Another dye, MHI-148, can be used for a similar labelling protocol, but QuatCy reacts faster with all proteins studied, except albumin; it emerges here that this is because MHI-148 instantly forms of a non-covalent complex with albumin, but QuatCy does not. Labelling with QuatCy has advantages insofar as it is over five times brighter, and much more photostable, than MHI-148, and combination labelling with this dye pair will allow multiplexing in the near-IR region.
- Thavornpradit, Sopida,Usama, Syed Muhammad,Lin, Chen-Ming,Burgess, Kevin
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supporting information
p. 7150 - 7154
(2019/08/07)
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- CONJUGATES OF KINASE INHIBITORS AND CYANINE DYES
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The present disclosure provides conjugates of kinase inhibitors and cyanine dyes, as well as related compositions, methods and uses.
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Paragraph 0406
(2019/11/22)
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- A fragment-based approach towards the discovery of N-substituted tropinones as inhibitors of Mycobacterium tuberculosis transcriptional regulator EthR2
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Tuberculosis (TB) caused by the pathogen Mycobacterium tuberculosis, represents one of the most challenging threat to public health worldwide, and with the increasing resistance to approved TB drugs, it is needed to develop new strategies to address this
- Prevet, Hugues,Moune, Martin,Tanina, Abdalkarim,Kemmer, Christian,Herledan, Adrien,Frita, Rosangela,Wohlk?nig, Alexandre,Bourotte, Marilyne,Villemagne, Baptiste,Leroux, Florence,Gitzinger, Marc,Baulard, Alain R.,Déprez, Benoit,Wintjens, René,Willand, Nicolas,Flipo, Marion
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p. 426 - 438
(2019/02/20)
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- Fused tricyclic hepatitis virus inhibitor and application thereof
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The invention belongs to the field of medical chemistry, relates to a fused tricyclic hepatitis virus inhibitor and application thereof, and particularly, provides a compound of the general formula I or pharmaceutically acceptable salt, isomer, solvate, crystal or prodrug thereof, and a medicine composition containing the compounds and application of the compounds or the composition in medicine preparation. The compound has the good inhibiting activity on hepatitis C virus, meanwhile has the low toxicity on host cells, and is high in effectiveness, good in safety and likely to become the medicine for treating and/or preventing diseases relevant to HCV infection.
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- Electrochemical access to 8-(1-phenyl-ethyl)-1,4-dioxa-8-aza-spiro[4.5] decane-7-carbonitrile. Application to the asymmetric syntheses of (+)-myrtine and alkaloid (+)-241D
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The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (-)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation-reduction decyanation process. α-Amino nitrile 6 was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1-3 stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl4·(Et2O)2 complex in diethyl ether. When appropriate, the ers were determined by proton and carbon NMR spectroscopy utilizing (+)-tert-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.
- Vu, Van Ha,Louafi, Fadila,Girard, Nicolas,Marion, Ronan,Roisnel, Thierry,Dorcet, Vincent,Hurvois, Jean-Pierre
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p. 3358 - 3373
(2014/05/06)
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- Spiroalkene carboxamide derivatives and their use as chemokine receptor modulators
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The present invention is directed to compounds of Formula (I) below, which are antagonists to the chemoattractant cytokine receptor 2 (CCR2), and/or 5 (CCR5), pharmaceutical compositions, and methods for use thereof.
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Page/Page column 45
(2012/10/18)
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- SPIROALKENE CARBOXAMIDE DERIVATIVES AND THEIR USE AS CHEMOKINE RECEPTOR MODULATORS
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The present invention is directed to compounds of Formula (I) below, which are antagonists to the chemoattractant cytokine receptor 2 (CCR2), and/or 5 (CCR5), pharmaceutical compositions, and methods for use thereof.
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Page/Page column 55
(2012/10/18)
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- SUBSTITUTED-QUINOXALINE-TYPE-PIPERIDINE COMPOUNDS AND THE USES THEREOF
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The invention relates to Substituted-Quinoxaline-Type Piperidine Compounds, compositions comprising an effective amount of a Substituted-Quinoxaline-Type Piperidine Compound and methods to treat or prevent a condition, such as pain, comprising administeri
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Page/Page column 286
(2009/04/25)
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- Photoswitchable catalysts: Correlating structure and conformational dynamics with reactivity by a combined Experimental and computational approach
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Photocontrol of a piperidine's Bronsted basicity was achieved by incorporation of a bulky azobenzene group and could be translated into pronounced reactivity differences between ON- and OFF- states in general base catalysis. This enabled successful photomodulation of the catalyst's activity in the nitroaldol reaction (Henry reaction). A modular synthetic route to the photoswitchable catalysts was developed and allowed for preparation and characterization of three azobenzene-derived bases as well as one stilbene-derived base. Solid-state structures obtained by X-ray crystal structure analysis confirmed efficient blocking of the active site in the E isomer representing the OFF-states, whereas a freely accessible active site was revealed for a representative Z isomer in the crystal. To correlate structure with reactivity of the catalysts, conformational dynamics were thoroughly studied in solution by NMR spectroscopy, taking advantage of residual dipolar couplings (RDCs), in combination with comprehensive DFT computational investigations of conformations and proton affinities.
- Stoll, Ragnar S.,Peters, Maike V.,Kuhn, Andreas,Hecht, Stefan,Heiles, Sven,Thiele, Christina M.,Goddard, Richard,Buehl, Michael
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supporting information; experimental part
p. 357 - 367
(2009/06/18)
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- Photoswitching of basicity
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(Figure Presented) Smart bases: By using a photochromic azobenzene-derived blocking group, a piperidine base can be switched between a sterically shielded, inactive form and an accessible, reactive form (see picture; C dark gray, H light gray, O red, N blue). Thus, light can be used for the reversible external modulation of ground-state basicity and hence activity in general base catalysis.
- Peters, Maike V.,Stoll, Ragnar S.,Kuehn, Andreas,Hecht, Stefan
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supporting information; experimental part
p. 5968 - 5972
(2009/03/11)
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- Synthesis of a naphthyridone p38 MAP kinase inhibitor
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Compound 1 is a p38 MAP kinase inhibitor potentially useful for the treatment of rheumatoid arthritis and psoriasis. A novel six-step synthesis suitable for large-scale preparation was developed in support of a drug development program at Merck Research Laboratories. The key steps include a tandem Heck-lactamization, N-oxidation, and a highly chemoselective Grignard addition of 4-(N-tert-butylpiperidinyl)-magnesium chloride to a naphthyridone N-oxide. The N-oxide exerted complete chemoselectivity via chelation in directing the Grignard addition to the α position as opposed to 1,4-addition on the enelactam. The dihydropyridyl adduct was in situ aromatized with isobutylchloroformate followed by heating in pyridine. Syntheses of Grignard precursor, N-tert-butyl-4-chloro-piperidine, were accomplished via transamination with a quaternary ammonium piperidone or via addition of methylmagnesium chloride to an iminium ion. Utilizing this chemistry, multi-kilogram preparation of compound 1 was successfully demonstrated. American Chemical Society.
- Chung, John Y. L.,Cvetovich, Raymond J.,McLaughlin, Mark,Amato, Joseph,Tsay, Fuh-Rong,Jensen, Mark,Weissman, Steve,Zewge, Daniel
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p. 8602 - 8609
(2007/10/03)
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- 3-‘4-HETEROCYCLYL -1,2,3,-TRIAZOL-1-YL!-N-ARYL-BENZAMIDES AS INHIBITORS OF THE CYTOKINES PRODUCTION FOR THE TREATMENT OF CHRONIC INFLAMMATORY DISEASES
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Disclosed compounds of formula (I), which inhibit production of cytokines involved in inflammatory processes and are thus useful for treating diseases and pathological conditions involving inflammation such as chronic inflammatory disease. Also disclosed are processes for preparing these compounds and pharmaceutical compositions comprising these compounds.
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Page/Page column 135
(2008/06/13)
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- Cyclic hexapeptides having antibiotic activity
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This invention relates to new polypeptide compound represented by general formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in the description or a salt thereof which has antimicrobial activities (especially, antifungal activities), inhibitory activity on β-1,3-glucan synthase, to process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for prophylactic and/or therapeutic treatment of infectious diseases including Pneumocystis carinii infection (e.g. Pneumocystis carinii pneumonia) in a human being or an animal.
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- Synthesis of 1-tert-butyl-4-chloropiperidine: Generation of an N-tert-butyl group by the reaction of a dimethyliminium salt with methylmagnesium chloride
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(Chemical Equation Presented) Two efficient routes to 1-tert-butyl-4- chloropiperidine are described. In the first route, the key thionyl chloride mediated chlorination reaction features the use of tetrabutyl-ammonium chloride as an additive that effectively suppresses the formation of an elimination-derived side product. In the second route, a novel alternative synthesis of 1-tert-butyl-4-chloropiperidine was developed in which the tertiary butyl group on the nitrogen is efficiently generated through the addition of methylmagnesium chloride to a dimethyliminium salt in 71% overall yield.
- Amato, Joseph S.,Chung, John Y. L.,Cvetovich, Raymond J.,Gong, Xiaoyi,McLaughlin, Mark,Reamer, Robert A.
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p. 1930 - 1933
(2007/10/03)
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- Acrylate as an efficient dimethylamine trap for the practical synthesis of 1-tert-butyl-4-piperidone via transamination
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Efficient trapping of dimethylamine was the key to success in the transamination of 1,1-dimethyl-4-oxopiperidinium iodide with tert-butylamine to afford 1-tert-butylpiperidin-4-one in high yield. The use of sodium acrylate was found to provide an elegant way to both trap dimethylamine and provide a convenient method to allow purification in the subsequent extraction.
- Amato, Joseph S.,Chung, John Y. L.,Cvetovich, Raymond J.,Reamer, Robert A.,Zhao, Dalian,Zhou, George,Gong, Xiaoyi
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p. 939 - 941
(2013/09/03)
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- INTRAMOLECULAR CATALYSIS IN THE ENOLISATION OF AMINOKETONES
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Measurements are reported on the rates of halogenation of the aminoketones PhCO(CH2)nNC5H10, with n = 1-3 , and N-methyl-4-piperidone (V), and their N-methyl derivatives.The reactions are zero order with respect to halogen concentration, with the rate-determining step being the formation of the enol or enolate ion.Large rate accelerations relative to acetophenone and cyclohexanone were observed, and these cannot be explained entirely in terms of inductive (through-bond) effects of =NH+, =NMe+, or =N groups.Other important factors are (i) intramolecular stabilization of the developing negative charge by the positive ammonium ion, the maximum effects being observed for (II); (ii) electrostatic interactions with negatively charged catalysts; (iii) direct proton transfer from the ionising C-H group to =N, acting as an intramolecular base catalyst.Evidence for a direct proton transfer was found only in reactions of the γ-substituted aminoketone (IV).
- Cox, Brian G.,Maria Paolo De,Fini Adamo
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p. 1647 - 1652
(2007/10/02)
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