- Total synthesis of RS-42358 and analogs using lateral lithiation
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A short synthesis of the 5-HT3 receptor antagonist RS-42358 was developed based on the condensation of lactone 2 with S-3- aminoquinuclidine. The position 2 analogs of RS-42358 were made by condensing various primary amines with lactone 2. The key step in the synthesis of lactone 2 was lateral lithiation of diethyl amide 7 using n-BuLi in THF.
- Kowalczyk, Bruce A.
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Read Online
- Towards a TREK-1/2 (TWIK-Related K+ Channel 1 and 2) dual activator tool compound: Multi-dimensional optimization of BL-1249
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This letter describes a focused, multi-dimensional optimization campaign around BL-1249, a fenamate class non-steroidal anti-inflammatory and a known activator of the K2P potassium channels TREK-1 (K2P2.1) and TREK-2 (K2P1
- Iwaki, Yuzo,Yashiro, Kentaro,Kokubo, Masaya,Mori, Takahiro,Wieting, Joshua M.,McGowan, Kevin M.,Bridges, Thomas M.,Engers, Darren W.,Denton, Jerod S.,Kurata, Haruto,Lindsley, Craig W.
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Read Online
- N-Heterocyclic-Carbene-Catalyzed C–H Acylation via Radical Relay
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A method of N-fluorocarboxamide-directed N-heterocyclic-carbene (NHC)-catalyzed benzylic C–H acylation with aldehydes via the hydrogen atom transfer strategy is disclosed. This transformation involves a sequence of single-electron transfer, 1,5-hydrogen a
- Liu, Shiwen,Man, Yunquan,Xu, Bo,Zeng, Xiaojun
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supporting information
p. 944 - 948
(2022/02/05)
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- Facile Synthesis of Alkylidene Phthalides by Rhodium-Catalyzed Domino C?H Acylation/Annulation of Benzamides with Aliphatic Carboxylic Acids
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The Rh-catalyzed ortho-C(sp2)?H functionalization of 8-aminoquinoline-derived benzamides with aliphatic acyl fluorides generated in situ from the corresponding acids has been developed. This reaction initiated with 8-aminoquinoline-directed ortho-C(sp2)?H acylation, which was accompanied by subsequent intramolecular nucleophilic acyl substitution of amide group to produce alkylidene phthalides This approach exhibits high stereo-selectivity for Z-isomer products, and tolerates a variety of functional groups as well as aliphatic carboxylic acids with diverse structural scaffolds.
- Liu, Sien,He, Bangyue,Li, Hongyi,Zhang, Xiaofeng,Shang, Yaping,Su, Weiping
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supporting information
p. 15628 - 15633
(2021/10/05)
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- Heterocyclic compound and preparation and application thereof
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The invention relates to bromodomain inhibitors, and provides a compound represented by a general formula I, a pharmaceutically acceptable salt, an enantiomer, a diastereoisomer, an atropisomer, a racemate, a polymorph, a solvate or an isotope-labeled compound (including deuterium substitution) thereof, a preparation method thereof, a pharmaceutical composition containing the same, and applicationthereof in pharmacy.
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Paragraph 0294-0296
(2020/07/24)
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- Rh-Catalyzed annulations of: N -methoxybenzamides with ketenimines: Synthesis of 3-aminoisoindolinones and 3-diarylmethyleneisoindolinones with strong aggregation induced emission properties
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Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides furnished 3-aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-ones. The synthesized 3-(diarylmethylene)isoindolin-1-ones exhibited aggregation induced emissions in aqueous tetrahydrofuran solution and strong green-yellow emissions in solids.
- Zhou, Xiaorong,Peng, Zhixing,Zhao, Hongyang,Zhang, Zhiyin,Lu, Ping,Wang, Yanguang
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supporting information
p. 10676 - 10679
(2016/09/02)
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- PROCESSES FOR THE PREPARATION OF PALONOSETRON
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The present invention relates to novel processes for the preparation of N-[(3S)-1- azabicyclo[2.2.2]oct-3-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxamide of Formula I. The present invention further relates to processes for the preparation of palonosetron or its salts thereof using N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-5,6,7,8- tetrahydronaphthalene-1-carboxamide of Formula I as an intermediate.
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Page/Page column 14
(2011/02/24)
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- PREPARATION OF CRYSTALLINE PALONOSETRON HYDROCHLORIDE
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Processes for the preparation of palonosetron hydrochloride and its crystalline forms.
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Page/Page column 21
(2010/06/15)
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- Processes for preparing palonosetron salts
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The present invention provides processes for preparing Palonosetron salts, especially, the hydrochloride salt and intermediates used to prepare Palonosetron salts.
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Page/Page column 10
(2008/12/08)
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- SUBSTITUTED BENZOYLAMINO-INDAN-2-CARBOXYLIC ACIDS AND RELATED COMPOUNDS
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The present invention relates to A compound of the formula Ia wherein in any of its stereoisomers forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, wherein the substituents are as described herein. The inventive compounds have CXCR5 inhibitory activity are particularly useful in treating or preventing various inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, lupus, Crohn's Disease, associated with the modulation of the human CXCR5 receptor.
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Page/Page column 66-67
(2009/01/24)
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- N-(2-phenyl-4-piperidinybutyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxamides and their use as neurokinin 1 (NK1) and/or neurokinin 2 (NK2) receptor antagonists
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Compounds of formula (I), wherein R2is a 5,6,7,8-tetrahydronaphth-1-yl group which may be substituted (the remaining groups defined herein), and pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of a condition where antagonism of the NK1 and/or NK2 receptors is beneficial.
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- Aminoalkylindoles: Structure - Activity Relationships of Novel Cannabinoid Mimetics
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Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands.In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of 3H>Win 55212-2 (5).Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists.The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (H) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position.A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist.Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids.The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors makes sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid.Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).
- Eissenstat, Michael A.,Bell, Malcolm R.,D'Ambra, Thomas E.,Alexander, E. John,Daum, Sol J.,et al.
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p. 3094 - 3105
(2007/10/02)
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- O-Methylarenehydroxamates as Ortho-Lithiation Directing Groups. Ti(III)-Mediated Conversion of O-Methyl Hydroxamates to Primary Amides
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Reaction of O-methyl benzohydroxamates 2a-c with sec-butyllithium in the presence of TMEDA at -40 deg C regiospecifically generates the highly reactive N,ortho-dilithiated species (e.g. 3).These dilithio species react avidly with a wide spectrum of electrophilic reagents, including alkyl halides, givind adducts which on reduction with TiCl3 are converted into ortho-substituted primary benzamides in excellent yields.Ortho lithiation of O-methyl benzohydroxamates is thus formally equivalent to ortho lithiation of primary benzamides themselves.The utility of these synthetic operations is enhanced by the well-known facility with wich the primary amide moiety can be transformed into other useful functional groups.The conversion of O-methyl hydroxamates to primary amides is shown to be general, as exemplified by transformation of 14a-f to 15a-f.O-Methyl-2-methylbenzohydroxamate (4a) undergoes regiospecific dilithiation on nitrogen and on the methyl group when treated with sec-butyllithium at -70 deg C.These dilithio species react with DMF or "Weinreb-type" amides to give condensation products wich cyclize to N-methoxyisoquinolin-1(2H)-ones under mildly acidic conditions.Removal of the N-methoxy moiety under conditions analogous to those used for O-methyl benzohydroxamate provides N-unsubstituted isoquinolin-1(2H)-ones with high overall efficiency.This process is exemplified by the synthesis of isoquinolin-1(2H)-one 9a, its 3-n-butyl congener 9b, and the tricyclic isoquinolin-1(2H)-ones 20a and 20b from O-methyl 2-methylbenzohydroxamate (4a).
- Fisher, Lawrence E.,Caroon, Joan M.,Jahangir,Stabler, S. Russell,Lundberg, Scott,Muchowski, Joseph M.
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p. 3643 - 3647
(2007/10/02)
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- 2-(Quinuclidin-3-yl)pyrido[4,3-b]indol-1-ones and isoquinolin-1-ones. Potent conformationally restricted 5-HT3 receptor antagonists
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Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series,2-(quinuclidin-3-yl)tetrahydropyrido[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridge
- Clark,Miller,Berger,Repke,Weinhardt,Kowalczyk,Eglen,Bonhaus,Lee,Michel,Smith,Wong
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p. 2645 - 2657
(2007/10/02)
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